United States Patent (19) (11) 4,146,454 Haber (45) 'Mar. 27, 1979

(54) ELECTROMOLECULAR PROPULSION N. 4,030,995 6/1977 Starkweather ...... 204/180 SX DVERSE SEMCONDUCTIVE MEDIA Primary Examiner-Arthur C. Prescott 75 Inventor: Norman Haber, Old Tappan, N.J. 57 ABSTRACT (73) Assignee: Haber Instruments, Inc., Palisades This application is directed to an electromotive process Park, N.J. for exciting a chemical species which includes orientat ing, re-positioning and transporting and for the separa * Notice: The portion of the term of this patent tion of chemical species on a support. Unlike conven subsequent to Oct. 5, 1993, has been tional semiconductive technology in the solid state and disclaimed. amorphous state, the present process is directed to elec (21) Appl. No.: 707,532 trically induced molecular transport in semiconductive media, as distinct from charge transport alone. The (22) Fied: Jul. 22, 1976 semiconductive medium is generally of the liquid, gas Related U.S. Application Data or gel form. The process of this invention is characterized by a high (63) Continuation-in-part of Ser. No. 102,120, Dec. 28, mobility rate in the separation process which is 1970, Pat. No. 3,989,298. achieved by tailoring a semiconductive medium for (51) Int. Cl’...... GON 27/26 operation over a wide range of voltages at low current (52) U.S. C...... 204/180 S; 204/180 R; density. The voltage applied is preferably in the range 204/180 G; 204/299 R; 23/230 B; 424/12 of about 0.05 to about 25,000 volts/cm. The semicon 58) Field of Search ...... 204/180 R, 180 S, 180 G, ductive media used in this invention generally comprise 204/299, 181; 424/12; 23/230 B several components which are chosen to give a current density in the range of about 0.001 to 400 micro (56) References Cited amp/cm on filter paper as a substrate. The media U.S. PATENT DOCUMENTS should also have a high boiling point. A further aspect of the process is that an external cooling means is not

3,042,597 7/1962 Schumacher ...... 204/180 R 3,255,100 6/1966 Raymond ...... 204/180 G ordinarily required. 3,567,611 3/1971 Michel et al. ... or 204/80 G 3,964,992 6/1976 Krotz ...... 204/180 G X 35 Claims, No Drawings 4,146,454 1. 2 related, though unidentically structured, molecules. ELECTROMOLECULAR PROPULSON IN The characteristic mobility of a substance in cm/sec DVERSE SEMCONDUCTIVE MEDIA may be used to classify or identify substances. The great degree of molecular resolution or differentiation may be THE INVENTION accomplished over the distance of a few inches in a This application is a continuation-in-part of copend matter of seconds or minutes wherein proportionately ing application Serial No. 102,120, filed December 28, less time is required over small instances or by the use of 1970, now U.S. Pat. No. 3,984,298. higher. voltages. I have discovered that certain low This invention pertains to a method of exciting a current levels are near optimum for the EMP process chemical species to achieve mobility for orientating, 10 and are defined herein as threshold level function de repositioning and transporting the species and for sepa pendent upon the molecular nature of the materials ration among species achieved by operation at the ap involved. The threshold refers to excitation level states propriate conductivity range of the media and espe in a solvation-adsorption system. The usual observed cially within the semiconductive range when induced ranges are 2x10 to 1.6X 10 amp/cm for a cellu by means of intense electrical fields at or near minimum 15 lose substrate. Such threshold levels refer to minimal and optimum current levels. Such systems are charac current requirements for initiating the EMP process and terized by extremely fast molecular motion, or trans are usually close to the optimum current requirements port, hereinafter called electromolecular propulsion for a given system. The semiconductive range refers to (EMP), as well as by great differentiation or resolution methods to achieve suitable conductivity at high volt of molecular species. Such resolution is capable of ac 20 age at the threshold range. The media used are capable complishing very refined analytical separations. of sustaining high voltage electrical fields and are tai By comparison with conventional techniques, hereto lored to have a chemically adjusted and/or controlled fore unobtainable or unique mobilities as well as system level of conductivity internal to the mobile phase and in versatility can be achieved. This invention provides a combination with the substrate, by techniques consis method for inducing mobility of molecules previously 25 tent with the various electrical, chemical and operative considered nonmobile due to their nonpolar nature. In requirements of the working system. the case of polar molecules, such as certain metal deriv Under such conditions an intense compulsive re atives, a greater resolution is obtained than that sponse with very fast mobility or orientation and high achieved with conventional conductive or aqueous resolution separation of molecular types are readily electrolytes. These, plus additional useful factors favor 30 achieved. Such systems are very convenient and advan ing this technique, permit exceedingly high resolution tageous to operate. Their efficiency is high; heat loss is separation or purification of different types of molecu a minimum, and they are applicable within aqueous, lar species to be efficiently and very rapidly achieved. hydrophobic and otherwise non-aqueous media. Suitable detection and/or separation means gives this This process may be accomplished as a liquid-state process an important utility for analytical, purification, 35 semiconductive transport or gaseous state semiconduc and production procedures. It also serves as a research tive transport. Due to its ability to effect molecular tool for the study, characterization and elucidation of transpositions and its use of a mobile phase, it is a semi structural and physical-chemical attributes of chemical conductive fluidic, process. This distinguishes it from systems, materials and their interactions. the sessile solid state and amorphous semiconductive An aspect of this invention pertains to the preparation 40 systems. By virtue of its effect upon the electromolecu of suitable media and systems, within which the semi lar nature of materials through induction by and reac conductive molecular transport can be reliably accom tion to suitably intense electrical fields this process has plished. This can be performed in various media; it applications to major classes of known molecular mate being generally convenient to utilize liquids for the rials including inorganic ions, organic molecules, col mobile phase. The conductivity of the entire system or 45 loids, and crystalloids. Thus, this process is applicable process is brought within the semiconductive range by to inorganic materials such as derived from iron, cop adjusting the conductivity level of the media constitut per, nickel, cobalt, rare earths, heavy metals, zirconium, ing the mobile phase. Very high voltages may be sus and the separation of ionic-solvate species of metal tained at low current levels such that the thermoelectric derivatives. It is also applicable to other materials such heat buildup (IRT) nevertheless permits usage of 50 as proteins, antibiotics, vitamins, antihistamines, amino readily available materials and techniques for working acids, dyestuffs and blood constituents. systems. In contrast to conventional electrochemical By virtue of the extremely great resolution which can transport methods, in this invention very minute current be obtained by application of EMP and the very great levels are actually required which correspond to the speed with which such separations can be achieved, and semiconductive nature of the process. This often pre 55 the various types of systems in which the process can be cludes the need for employing external heat convective applied, it offers advantages and applications to various means and permits small working configurations and fields and operative procedures, including: analytical small power supply size requirements. Another advan chemistry, quality control, clinical chemistry; research; tage of the process is that at the low heat levels of this preparative chemistry; physical chemistry; purification; invention thermal interference is minimized. The very extraction; process control; applied chemistry; and low current levels which suffice in this invention are semiconductive technology. near optimum for molecular movement as induced by By way of illustration, in preparative chemistry, the attractive-repulsive interaction within the electric chemical reactions conducted under suitable EMP con field, and, under such conditions, a very intense migra ditions can be used to displace reaction equilibria to tory effect can be induced which is proportional to the 65 favor certain yields. It offers a means for selective de voltage potential applied. This migratory effect is char pletion of equilibrium product from the sphere of the acteristic for the molecular nature of the material and reaction zone, or of contaminants, or byproducts. In may be sharply differentiated from even similarly or extraction, EMP acts as a minimal time consuming pro

is 4,146,454 3 4. cess especially from thin-walled materials, particulates, 5. Operation at or near the low threshold levels can or porous substances. In applied chemistry, it is useful be achieved with an overall high electrical propul where very rapid and/or selective penetrative process sive efficiency. These thresholds are characteristic ing is desired, e.g., in dyeing or destaining fabrics. The for a material and generally exist at very low dyes or other detectable molecules in a mixture may be 5 power levels. This then defines an operational pro individually deposited in a preselected or ordered pat pulsive efficiency whereby this process is capable tern by control of their EMP response. of use at power levels just sufficient to effect the Another advantage of the invention is that it permits molecular species' propulsion, and wherein the the separation, characterization, or study of molecular electrothermal losses approach negligible values. types by virtue of the differential threshold levels. It 10 Actually, thermal increments become negligible at permits control at different levels under various condi very low power levels, especially in a low effi tions of pH, temperatures, different media, or other ciency electrothermal system. Counteracting fac internal or external factors. An application of this tors include evaporative cooling, reservoir heat would be a process which is controllable by first operat capacity, thermal convection, and in certain situa ing the system at the lower threshold level to effect the 15 tions dissipation by convective factors such as elec first separation; then going on to subsequent levels in troendosmotic streaming. By the controlled opera order to complete the resolution. tion at increasing threshold levels the molecular Major operative features for the practice of the inven species in turn will be inducted into propulsion at tion are: their appropriate and characteristic level irrespec 1. Adjusting the operative phase to the semiconduc tive of other materials which may be present. This tive range to provide operation at or near molecu provides an additional high resolution technique lar threshold levels and maximum or convenient which is capable of differential molecular discrimi voltage levels capable of being sustained by the nation. This discriminatory process is further en system. hanced by virtue of the propulsion rate also being 25 characteristic for the molecular species involved. 2. Establishing the optimum current level at or near This migratory or propulsive rate can be caused to the molecular threshold level at the given voltage vary substantially by modification of the media. for effective molecular resolution. Appropriate to the mechanism of propulsion thresh 3. Utilizing those components within the system and old it is noted that this behavior determines that point arranging the system characteristics such that 30 where the molecular attraction or adhesion to the sub overall stability, reproducibility, and safety, are strate (surface) is counteracted by the total energy in attained. put. This is comprised of the external electrical energy A useful analogy of this phenomena and its relation input plus what other distribution is due to additional ship to electrochemistry is the comparison of solid state partition functions present. The molecules are then free semiconductive physics with its earlier thermionic elec 35 to migrate or be swept by electrical attraction or other trical technology. Some similarities may be noted from convective factors. The electrical characteristics of the the following characteristics of the EMP process. systems show a nonlinearity as the current will gradu 1. Power supply wattage (and size) requirements are ally rise after the initial application of a given voltage. minimized. The preferred systems rapidly stabilize and remain in 2. Minimal electrothermal losses permit small work 40 electrical equilibrium during the separatory process, ing dimensions and increased field intensities; this although the process may be carried out as gradual contributes to fast resolution times at low distortion changes occur in the electrical characteristics. In cases levels. where a lack of stability causes difficulty but the me 3. The deteriorating influence upon the system as a dium is otherwise considered useful, the rate of change result of brute force power requirements, and its 45 in resistance of the system may be reduced by the addi attendant heat effects, is eliminated. For example, tion of an external resistance of sufficient magnitude, for at higher current densities than those used in this example, about equal to or greater than the magnitude invention the mobility and resolution character of of the internal resistance of the system. Alternatively, molecuar species may be altered. an active electrical element may be utilized which is 4. The degree and manner of the electrical utilization 50 capable of sensing the current-voltage or temperature is not restricted to the more conventional conduc levels within a system and serve to regulate these fac tivity modes, such as aqueous electrolyte ion trans tors or changes therein by means of control of the port in liquid phase. Therefore, vast numbers of power source. This procedure is also of value as a safety different types of materials may be acted upon, feature. studied, or utilized in the EMP process. This in 55 Investigation of components for media formulation cludes materials and systems whose electrical or has shown that certain compound combinations are not ionic contribution would be thought meager from feasible for use in EMP if stable current levels are de anticipation of their molecular structures. Addi sired. When a constant voltage is applied, these combi tionally, a broad range of nonaqueous, hydropho nations continually exhibit a different resistance as if a bic, and otherwise nonpolar substances as well as 60 capacitor were being charged. This effect may be illus ionic, polar, covalent, aprotic, or other types of trated by considering the variation of current with time conductive substances may be included. This semi at constant voltage, for a time on the order of several conductive fluidic process thereby serves as a new seconds or minutes. and convenient tool to explore various aspects A material or mixture with electrical characteristics within these fields, some of which are relatively 65 of a first type A (continually increasing current) may unknown; as well as to elucidate molecular struc eventually suffer arcing over. A material or mixture of ture, excitation states, electromolecular interaction a second type C (increasing current), and then decreas and nature of materials. ing current after a point) is subject to evaporative heat 4,146,454, 5 6 ing and so eventually burns, chars or dries out. A mate ments, porous materials and powders. Ion exchange rial or mixture of type a third B initially increasing media, permaselective and membrane barriers, dialytic current to a relatively constant value is a preferable membranes, molecular sieves and specific ion source media from the point of view of electrical control be materials are suitable as supports or barriers. The pro cause it allows reproducibility of runs and readjustment cess may be carried out continuously or by the batch of the electrical characteristics is not a concern. Materi technique. als exhibiting electrical behavior of type A may be de Many substances are relatively dielectric; of these the liberately chosen as media components to offset the nonpolar organics constitute a vast grouping. Some of properties of a media which otherwise exhibits type C these exhibit intermediate ranges of conductivity or are behavior, and vice versa. Also, the electrical character 10 susceptible to appropriate adjustment of their conduc istics of a given compound may change depending on tive nature by addition of relatively small amounts of the other substances with which it is mixed. Examples adjuncts. This may be likened to the process of doping of compounds illustrating type A behavior in some or implantation used with solid-state devices. Other mixtures and type B behavior in others is given below. means may include irradiation, polarization interaction, Generally one would choose a media component which 15 injection or radioactive or charged particulates, photo exhibits type B behavior in conjunction with the other activation, superposition of AC fields, magnetic fields components in the system. . or other energizing means. These energizing fields may be oriented at different angles with respect to the DC COMPOUNDS TYPE BEHAVIOR field. For example, an AC field superimposed upon the N,N-dimethylacetamide in water DC field used in this invention may be used to impart N,N-dimethylacetamide in formamide N,N-dimethylformamide in water additional mobility to chemical species within a me 1,2-propanediolcyclic carbonate in water dium. Pulsed DC or the superimposition of pulsed DC ethylene carbonate in water 3-methyl sulfolane in water may also be used. A relatively polar material can be 2-pyrrolidinone in water N-methylformamide in water A 25 used as the medium, such as aqueous solutions, by limit N-methylacetamide in water ing the ionic content of the system to achieve the de tetrahydrofurfuryl alcohol in water, sired conductivity level. Also, suppressive substances tetrahydrothiophene dioxide in formamide diacetone alcohol in formamide can be added to a conductive system, desirable materi diacetone alcohol in thiodiethylene glycol als being those which exert a suppressive effect beyond cellosolve in formamide . . . , the mere dilution effect which their presence contrib cellosolve in thiodiethylene glycol 30 utes to the system. Further, the suppressive effect of nonpolar materials used in comixture with otherwise The EMP process differs from the prior art processes conducting systems offers a very general and useful of electrophoresis and dielectrophoresis in a number of approach to the control of conductivity. It is important respects. EMP exhibits non-linear electrical characteris to note that in regard to all of these techniques other tics departing from the Kohlrausch requirement for 35 factors may favor certain additional properties and electrolytes and from Ohm's Law. Specifically, the characteristics of the materials employed appropriate following characteristics are observed with EMP for the nature of the application, such as miscibility, (1) non-doubling of current with doubling of voltage compatibility, toxicity, boiling point, melting point, (2) non-constant resistance with time reactivity, cost, removability, dialyzability and osmolal (3) non-constant resistance with voltage or current Furthermore, the EMP response does not seem to be ity. A high dielectric constant material is often pre very affected by viscosity; and the EMP response is ferred due to its ability to maintain the charges formed enhanced by increasing the dielectric constant of the in the system (involving solvation or interaction) or solution while the electrophoretic mobility is inversely charges otherwise acquired or induced upon chemical proportional to dielectric constant so EMP may be 45 species. The attainment of a controlled level of conduc practiced at dielectric levels far exceeding those practi tivity may be further controlled or adjusted by the cable with electrophoresis. Thus EMP in media with a simultaneous consideration of other system parameters, dielectric constant up to 190 has been practical, e.g., in such as pH, physical state and temperature. N-methylacetamide. Mixed solvents may be used with the intermediation The migration rate in cm/sec of chemical species 50 of a coupling agent, usually of a semipolar cosolvent transported by EMP is markedly superior to the rates nature. The term semipolar is used for a material which achieved with dielectrophoresis and electrophoresis shows some conductivity, which will increase upon having a significantly greater value in the semi-conduc dilution with water (or other similarly polar material), tive range of values of conductivity. and which will increase upon addition of a soluble ionic It is thought that the EMP process relies on proton 55 salt. Thus, in the present invention the solvation of a donor/acceptor interactions and electron charge trans strongly ionic material into a nonpolar one by means of fer complexes for transport. See R. Foster, Organic a semipolar material will generally produce only a Charge-Transfer Complexes (1969). minor conductivity increase, whereas the solution of In practical terms, a key consideration in this process the ionic material in the semipolar solvent alone may be pertains to the use of a relatively nonconductive me moderately conducting. In effect, the nonpolar material dium. Various different media and techniques may be may be viewed as suppressing the capabilities for mod used to achieve the requirements of the semiconductive erate conduction to form a three-way system. The ranges employed. Conduction can be carried out in three-way system therefore comprises an inert base, a solids, semisolids, such as gels, as well as in the gaseous conductivity agent and a semipolar material, such as, phase, aerosols, foams and liquids. Also, combinations 65 respectively, xylene, ammonium bromide and dimethyl of these are practical as are melts, high temperature formamide. Further, a considerable increase in the melts, pseudo crystals (para crystals and mesomorphic amount of the semipolar solvent may only minimally materials), ices, slushes, glasses, plastics, fibers, fila improve the conductivity. The addition of a relatively 4,146,454 7 8 small volume of a second type of semipolar solvent (a four-way system) can then effect a very substantial Electrical conductivity increase of the entire system. Neither co Characteristic solvent alone with the nonpolar material, without or Example Solvent Formulae (Stabilized) including the solvated ionic material, will approach the 5 0.3 ml. water, 0.2 ml. Sorensen Buffer (pH 7.0), 24.5 ml, propyl conductivity level so achieved. This technique for aug ene glycol. The amount of water menting the conductivity of essentially nonpolar mate in this type of system should preferably not exceed about 2%. KVAnna rials forms a convenient working basis for the use of 2.0 ml. dimethyl acetamide, 1.0 ml. substances such as xylene, p-cymeme, mineral oil and phenol, 25.0 ml. propylene glycol 8 KVAma chlorinated solvents. An illustration of a four-way sys 10 3 2.5 ml. formamide, 22.5 ml, pro tem is xylene, ammonium bromide, dimethyl acetamide pylene glycol. 5.5 KVAma and dimethyl formamide. The above effects also may be applied to systems Example 3 is excellent for dye resolution of the fol which are not readily ionizable and the components lowing mixture: saframin 0, toluylene red (neutral red) determined by such factors as dielectric constant and 15 and sodium riboflavin phosphate. This media is also proton donor capability of the solvating molecules. useful for separation of members of the rhodamine dye Whereas medium donor capability may give rise to stuff family. solvated molecules, a high donor capability in a high Unlike conventional ionic-transport processes the dielectric system readily tends to preserve the ionic mobilization of metal derivatives is not readily charges so created. Of particular use are media having 20 achieved, even when the metal derivatives are soluble dielectric constants above 10, which tend to maintain in the media. However, by adjustment of the media and charges formed by protondonor acceptor exchange. electrical characteristics in accordance with this inven The media used in this invention are characterized by tion a very fine resolution is obtained, which illustrates liquidity at or near room temperature, and sufficiently a new mode of operation as described herein. By suit high boiling points to withstand the process heat. The 25 able modification of the above solvent systems, metal boiling points are generally above 140 C., and prefera ion movement may be made practical, as in the follow bly above 165 C. The media need not be capable of ing systems. Examples of suitable metal ions are Cott, dissolving the chemical to which mobility is to be im Cu, Nitt from salts, such as the chlorides and ni parted, but solubility is preferable for separation of trates different molecular species. 30 This invention is further illustrated by the following Electrical examples directed to the separation of chemical species Characteristic in the indicated media. The apparatus consisted of a Example Solvent Formulae (Stabilized) high density polyethylene separation cell divided into 4. 10 ml. dimethyl formamide, 15 ml. 35 propylene glycol 10 KVAma two 15cc compartments; these being separated by a 5 10 ml. dimethyl formamide, 15 ml. space containing a support bridge for a spanning sup propylene glycol, 1 ml. triethanola port substrate. The cell was constructed to withstand mine 8 KWArna and provide security from the high voltage fields and conductive leakage of media under such fields and the Another approach is to use dithizone derivatives of wide range of strong and corrosive solvent materials metals such as cobalt, copper and nickel in solvent sys used herein. A platinum electrode in each compartment tems such as (4) and (5) above. was connected to a DC power source generally oper As ester based nonaqueous system is also satisfactory ated at 1.25 ma. The power source was capable of me as illustrated below. In place of the cellosolve in the tered operation at variable voltage levels in the ranges 45 medium, other related compounds can be used, such as of 0-100 ua, 0-1 ma, and 0-10 ma, for threshold studies hexyl cellosolve, methyl carbitol, cellosolve acetate, and operation of the processes described herein. A filter and carbitol acetate. paper wick in each compartment was connected to opposite ends of the filter paper substrate which ex Electrical tended across the top of the cell. The filter paper was 50 Characteristic five cm wide by ten cm long and except where stated Example Solvent Formulae (Stabilized) otherwise it was Whatman 3. Normally, the voltage 6 4 ml. formamide, 14 ml. cellosolve, drop in this system occurs substantially across the im 34 ml. dimethyl phthalate 5 KVAma pregnated support, for example from 70% to 90% or more. The cell was enclosed by a transparent cover. 55 The following examples show tailoring of the con A suitable solvent can be selected from the class of ductivity levels (doping) via nonaqueous salt methods low molecular weight glycols with a minor amount of and especially the additional influence of a second semi an additive to increase conductivity. The following polar material wherein n-butanol S is a saturated solu solvent systems are useful for relatively nonpolar dye tion of ammonium bromide in n-butanol. This medium is stuffs as well as other soluble organic materials. The illustrative of a four-way system discussed above, and is solvents listed were used for the separation of mixed useful for the separation of dyes and other compounds chemical species, such as dyes, Mercurochrome, and soluble therein. sodium riboflavin phosphate, at the voltage and current shown. The term "stabilized' is used to indicate that the electrical characteristics reached the indicated values 65 Electrical Characteristic and remained constant for the few minutes (generally Example Solvent Formulae (Stabilized) two to ten minutes) during which the separation process 7 5 ml. n-butano S, 30.5 ml, was completed. n-decanol, 2 ml. E-methyl-2- 4,146,454 9 10 -continued Electrical Electrical Characteristic Characteristic Example Solvent Formulae (Stabilized) Example Solvent Formulae (Stabilized) pyrrolidinone 14 KV/ma 5 11 21 ml. 1,2-propanediol cyclic 7.8-7.6 KV/1.25 ma carbonate +9ml. methoxy 6 min. run ethoxyethanol + 8ml T-Butyro The following solvent systems are useful for separa- ege +3 drops Nitric acid tion of metal ions and complexes; of the metal com plexes, dithizones, nitroso B-napthol, pyrocatechol vio- 10 let, rhodamine B, 8-hydroxy quinoline, and diben- Another similar system resolves nickel and cobalt zoylmethane derivatives were used. mixtures into pink and blue colored zones. This system is particularly fast with certain nonpolar dyestuffs giv ing 5 cm/min mobility rates at 7.5 KV levels. Operation Electrical at higher voltage levels would increase further the mo Example Solvent Formulae (Stabilized)E 15 bilityy rates: 8 30 s sey Ge. Aft carrie (1:30 in H2O) 64 KV/1.25 ma Example Solvent Formulae (Stabilized) 20 12 21 ml. 1,2-priopanediol cyclic 8.4-6.6 KVA1.25 ma The medium of Example 8 gave multizone resolution carbonate +9 ml, methoxy (5 minutes) with rare earth 8-hydroxyquinolinates such ESAC as Sc and Eu as well as other metals such as Ni. The drops nitric acid (1:30) heavy metal derivatives of dibenzoylmethane and rho damine showed good to excellent movement whereas' The rare earth groupings as well as hafnium and with heavy metal nitrates movement was very sparse zirconium represent the most difficult elements for reso and With hafnium (as chloride) not at all, Satisfactory lution. Further, just as hafnium and zirconium form a mobility was also obtained for Co+2, Cu+2, and Nit-2 particularly close pair, within the rare earths 3 major (as chlorides). W 30 paired groupings are known. The following systems are In the previous example the nickel chloride gave useful for the transition and heavy metal categories; three zones, with spot coloration of blue and violet, including salts of the rare earths and zirconium haf. Such reproducible effects demonstrate the very great nium elements, such as those having an atomic number resolution of the technique. This also points to the for- of 21 and greater. mation of a series of metal complexes, such as by proton 35 donor/acceptor exchange, and the ability of the tech nique to differentiate and resolve them. This unusual EGeistic capability is evidenced by another situation where not Example Solvent Formulae (Stabilized) only do multizones appear, but these appear as both (+) 13 15 ml. 1,2-propanediol cyclic 9.6-7.2 KVA1.25 ma or (-) moving entities. Mobility rates of +2 cm/min Evil hy 3 min, run were achieved with the following systems. gays: (1:30) Electrical 9haracteristic Example 13 was successfully repeated with the me Ex. Solvent Formulae (Stabilized) 45 dium substantially the same except that in each run the 9 15 EE :SY.Kiride) ethylene carbonate was replaced by one of the follow darie R 32 gad-) ing: tetrahydrafurfuryl alcohol, isophorone, cellosolve, + 3 drops nitric acid (1:30) Still -) cyclohexanone, and 2-ethylhexyl chloride 3. In a system comprising propanediol cyclic carbonate, 3 zones (-) 50 nitric acid, methoxy methoxy ethanol and tetrahydro 10 15 ml. methoxyethoxy ethanol y t furfuryl alcohol in proportions similar to those above at -- 15 ml. 1,2-propanediol cyclic CO (chloride) 500V and 100 ua, the dye saframin 0 moved readily, and carbonate +13 ml. ethylene. ones (+ and -) an orange contaminant remained immobile. This is an rate +3 drops nitric acid N, Ed -) example of the separation of components by reaching Cut' (chloride) 55 the threshold level for one compound in a mixture. (+ and -) Acidification with an inorganic acid is not essential as the following example illustrates. The medium of Example 10 also provided excellent mobility for salts of europium, lutetium, thallium and 60 cases, ytterbium. The position, mobility rate, and character of Example Solvent Formulae SE the zones obtained are characteristic for the material 14 12 ml. 1,2-propylene glycol 14 KVA.5 ma within the system under given conditions. Thus, in the -- 3 ml. dichloro acetic acid following system, nickel and cobalt (as chlorides) gave + 16 ml. ethoxyethoxy ethanol 1 to 2 zones respectively, whereas the mixture gave 3 65 zones corresponding to that of the individual metal Also, media containing bases such as triethanolamine constituents. Further, the zones had 3 colors with or y-picoline in place of an acid, have the capability for sharply distinguished pink and blue. the separation of metals. 4,146,454 11 12 The application of this invention to organic com As discussed further below, the foregoing systems pounds is further illustrated by the following systems can be improved in speed and degree of resolution using used for the separation of sulfa drugs, sulfamerizine, initiators, suppressants and/or stabilizers. sulfaquanidine and sulfamethazine. Operation of this process was also carried out by adding a sample to a bed of a gel made from agar, silica, and gelatin. This procedure has been used to separate Electrical Ex- Characteristic dyes, proteins and other types of organic compounds. ample Solvent Formulae (Stabilized) The media and electrical characteristics were similar to 15 20 ml. methoxyethoxy ethanol 5.8-5.0 KV/1.25 na those described in the preceding examples. Bulk separa -- 12 ml. 1-methyl 2-pyrrolidinone 4 min. run tions have also been carried out in a column with pow -- 0.8 ml. dichloracetic acid dered minerals or cellulose supports. A very useful system for non-polar substances, which The latter system, though found to be slow, was able has resolved isomers of methyl naphthalene and pro to yield differential zones with the dyestuff family of vided good resolution of Rhodamine B and 6G and food rhodamine 5 G, 6G, and B, as well as a mixture. dyes is: The following media gave high resolution of the 21 ml. propylene cyclic carbonate above dyes in 20-25 seconds and mobility rates in excess 9 ml. methoxyethoxy ethanol of 12 cm/min. 12 ml. tetrahydrofurfuryl alcohol 3 drops nitric acid (1:30) Electrica In the preceding formulae, use was made of various Characteristic types of compounds to perform or provide different Example Solvent Formulae (Stabilized) important functions. For illustrative purposes, a number 16 24 ml. 1,2-propanediol cyclic 13.2 KV/0.8 ma. of these are selected for arrangement into several cate carbonate + 12 ml. ethylene diacetate -- 6 ml. salicylaldehyde gories according to some of their common formulation + 3 drops nitric acid (1:30) functions. However, these categories are not rigidly defined limitations for the use of any compounds and The following two very fast related formulae ap some fall equally well across several category bound proach 20 cm/min mobility rates with excellent resolu aries. Thus, dimethyl phthalate is an example of a good tion: suppressant although it also functions as an inert base if

ELECTRICAL CHARACTERISTIC EXAMPLE SOLVENT FORMULAE (Stabilized) 17 24 ml. 1,2-propanediol cyclic 14.2 KV/ma carbonate -- 12 ml, ethylene diacetate + 6 ml. salicylaldehyde +.4 ml. ammonium bromide (saturated in methoxyethoxyethanol) 18 24 ml. 1,2-propanediol cyclic car- 13-12.6 KV/ma bonate + 12 ml. ethylene diacetate + 6 ml. salicylaldehyde + 2 ml. ammonium bromide (saturated solution methoxyethoxy ethanol) + 2 ml. tri butyl phosphate + 4 drops tetramethyl ammonium hydroxide (about 25% in methyl alcohol) 19 10 ml. tris-chloride (0.14m) -- 90 ml. 2 KV/ma water (sucrose to 67%) It is noted that urea or propylene glycol in such sys used as the base media. Further, it may act to insolubi tems, in concentrations to several molar, doesn't alter lize or limit mobility or influence other factors, thereby the conductivity although it may aid the mobility of enhancing resolution. Water is useful for a fairly active protein molecules. These substances act as a diluent or 50 solvent with moderate proton donor capabilities and suppressant and are useful in water solutions for bio high dielectric constant. This latter feature tends to chemical separations of substances such as proteins and maintain the charges once established. However, water enzymes. Albumin mobility in such systems can exceed is generally less useful as a major constituent at the that of glycol soluble dyestuffs, as shown below by the higher voltage levels in non-externally cooled systems data for migration from the origin. 55 due to its low boiling point.

ELECTRICAL CHARACTERISTIC EXAMPLE SOLVENT FORMULAE (Stabilized) 20 16 ml. tris-chloride (03M) 6 KV/2 ma -- 40 ml. propylene glycol Whatman il - 50 ml. glycerin Albumin 13 - Soluble dye 3/4' 6 min. run 21 10 ml. tris-chloride buffer 7.2 KVA2ma (0.03M) Cellulose ace -40 ml. propylene glycol tate +50 ml. methylcarbitol Paper 4,146,454 13 14 Table Inert Media-base Conductivity agent Characteristic: Perchloric acid minimal conductivity dichloracetic acid solvent, inert carrier, formamide solution limiter. ammonium bromide p-cymene pyridazine iodide mineral oil nitric acid n-decanol mercaptoacetic acid 1-octanethiol Active Media base xylene Characteristic: Inhibitors (suppressant) slight conductivity with tendency Characteristic: to enhance conductivity of neutral negative conductivity media base. influence. potent solubilizer, solvent tributyl phosphate 2-chloroacetamide dimethyl phthalate dimethyl formamide triacetin N,N-dimethylacetamide 2-ethylhexyl chloride 1-methyl-2-pyrrolidone Neutral media-base dimethyl sulfoxide Characteristic: ethylene cyclic carbonate slight to poor conductivity 2,5-hexanedione with tendency for active Modifying agents change in conductivity with isophorone dilution solvent, potent nitrobenzene solubilizer, coupling agent. salicylaldehyde T-butyrolacetone 4-hydroxy-4-methyl-2-kpentanone 1,2-propanediol cyclic carbonate ethylene diacetate propylene glycol -picoline 2-phenoxy ethanol o-dichlorobenzene 2-ethyl, 1,3-hexanediol tetrahydrothiophene 1,1-dioxide methoxyethoxyethanol Very Active Media Characteristic: strong conductivity influence, proton donor solvent action and scidity-alkalinity diethyl ethyl phosphonate N-cyclo-hexyl-2-pyrrolidone bis (2-methoxyethyl) ether Hexa methylene phosphoric triamide amino ethyl piperazine imino bis propylamine 2,2'-imino diethanol 2-amino ethanol triethylene tetramine triethanolamine mercaptopropionic acid mercaptoacetic acid

A starting point for developing and choosing a sol These materials are often used in comixtures to vent media for particular chemical species is to deter achieve their desired combined properties. Such formu mine those media which stabilize or are compatible with lations, aside from their electrical properties, achieve a the species and which exert a good to excellent partition very broad scope of applicability for different classes of coefficient in a standard chromatographic technique for 45 molecular species. the species on the substrate to be used at various pH. The following list of substances may be considered in The conductivity level is then adjusted for use in this three main categories, given below. Other factors to be process by adding the solvent as a major constituent to considered are a larger liquidity range, and dielectric a compatible media base system which has a properly constant, low viscosity, water compatibility and misci adjusted conductivity or, the conductivity of the sol SO bility and strong donor/acceptor influence or neutral vent can be tailored to form a media base system by the ity: use of the types of agents described in Table I. Mobility 1. The major grouping has boiling points at or above is normally achieved at about 1.25 ma, which generally 160 C. which are liquid at or near room tempera exceeds most threshold current levels. Further adjust ture. Generally they have good solvent action. ment may be necessary to initiate or refine the mobility 55 2. A number of the compounds listed have boiling of the species by the adjustment of the composition of points in the 130-160 C. range, or melting slightly the system as indicated above. For example, adjustment above room temperature. These are often used in may be made by the use of complexing agents, modify lesser percentages to modify systems. Also, they ing agents, similar solvents as determined by chromato often can be liquified with a minor amount of cosol graphic screening, by pH adjustment and less active Went. substrates (such as teflon). 3. The remainder are modifying agents, whose melt The compounds listed herein are representative of a ing points may be substantially higher and which much waster possible grouping of like or related materi are used in solution with other media. als useful as solvents, cosolvents, coupling agents with Based upon physical characteristics, chromato moderate, strong or nil effects on conductivity; many 65 graphic screening tests, and the media adjustment tech form complexes and metal adducts substantially modi niques described herein, the following compounds are fying the effective properties of the compounds or ma representative of the type of media component useful in terials involved. this process: 4,146,454 15 16 TABLE II Alcohols 2-aminoethanol 5-hydroxy-2-(hydroxymethyl)- 4H-pyran-4one 2-ethylaminoethanol 2-(2-ethoxyethoxy) ethanol 2,3-epoxy-1-propanol 2-2-(ethoxyethoxy) ethoxy) ethanol ethylene dinitrile tetraethanol 2-(2-butoxyethoxy) ethanol 2,2-iminodiethanol 1-2-(2-methoxy-1-methyl ethoxy)-1-methyl ethoxy 2-propanol d-menthol 2 mercaptoethanol n-butanol furfuryl alcohol 1,3 butanediol tetrahydrofurfuryl alcohol 1,4-butanediol 2,2'-oxydiethanol 2-(2-butoxyethoxy) ethanol 2,2'2'-nitrilotriethanol 2-butoxyethanol 1,1'1"-nitrilotri-2-propanol 2-(2-methoxyethoxy) ethanol 1-phenylethanethiol 2-methoxy ethanol 2,2'-(phenylimino)diethanol 3-methoxy-1-butanol 1,3-propane dithiol 2-butoxy-ethanol thiodiethanol 2-ethylhexane-1,3-diol 4-pyridine propanol t-butanol 2-nitro 1-propanol iso-amylalcohol 2-nitro-1-butanol caprylic alcohol 2-amino-2-(hydroxymethyl)-1, decanol 3-propanediol geranoil dehydroisophytol 2-methylamino ethanol glycerin 2-methyl-2-nitro-1, dehydrolinalool 3-propane diol 2-(hydroxymethyl)-2-nitro-1, thioglycerol 3-propanediol phenol 3-chloro-1,2-propanediol aziridine ethanol 2-amino-1-butanol hydroxy ethyl piperazine 2-amino-2-ethyl-1,3 propanediol piperazine ethanol 2-amino-2-methyl-l-propanol 2-Dimethyl amino-2-methyl-1-propanol tributyl phosphate sorbitol triethylphosphate glucose tricresyl phosphate SCOSS triphenyl phosphate ethylene glycol tri(2-ethylhexyl) phosphate propylene glycol tributoxyethyl phosphate dipropylene glycol o,oo-triethyl phosphoro thioate polyethylene glycol diethyl ethylphosphonate thiodiethylene glycol dibutoxyethyl sebacate 1-octanethiol 2-ethylhexylchloride 4-hydroxy-4-methyl-2-pentanone bis(2-(2-methoxyethoxy) ethoxyether inalool bis (2-methoxyethyl) ether linalool oxide 2-methoxyethyl acetate ethoxyethyl acetate Ethers, esters 2-(2-butoxyethoxy) ethylacetate dibutyl phthalate diethylene glycol mono methylether phenyl acetate diethylene glycol monoethyl ether dibutyl fumarate ethylene glycol monoethyl ether acetate dimethyl phthalate ethylene glycol mono ethyl ether acetate diethyl phthalate ethylene glycol monohexyl ether ethylactate diethylene glycol monoethyl ether acetate ethyl malonate diethylene glycol monomethyl ether di isooctylazelate ethyl cyanocetate di-2-ethylhexylazelate 3-acetyl-3-chloropropyl acetate methyloleate butyl chloroacetate tri (n-octyl) mellitate butyl lactate tri (n-decyl) mellitate butyl stearate acetyl tributyl citrate di tetrahydrofurfuryl adipate tributyl citrate ethylene diacetate tetra hydrofurfuryl oleate tris (chloroethyl) phosphate 2,2,4-trimethyl-1,3-pentanediol diisobutyrate di ethoxyethyl phthalate methoxyethyl ricinoleate glycerol monoacetate din-hexyl adipate glycerol tributyrate butane diol dicaprylate ethylene glycol dibenzoate diethylene glycol dibenzoate di propylene glycol dibenzoate polyethylene glycol (200) dibenzoate tri ethylene glycol diacetate bis (diethylene glycol mono ethyl ether) 17 4,146,454 TABLE II-continued phthalate bis (2-ethylhexyl) adipate 1,2-bis(2-chloroethoxy) ethane bis (2-chloroethyl) carbonate bis (2-methoxyethyl) phthalate di mercaptodiethyl ether glycol dimercaptoacetate dimethylthiodipropionate trimethylol ethane tri (3-mercapto propionate) penta erythritol tetra (3-mercaptopropionate) bis(2-chloro-isopropyl) ether glycerol triacetate glycerol tripropionate 1,2/1,3-glycerol diacetate hexyl acetate ethylmethyl carbamate N-methyl formamide hydroxyethyl acetate thioacetamide phenyltrimethoxysilane icramide trimethoxy trimethyl mercapto examethyl phosphoric silane triamide dimethylpolysiloxanes formamideine acetate 1,2-bis(2-methoxyethoxy) ethane Lactones, lactams, diones, and carbonates 2-(ethoxyethoxy) ethylacetate dibenzyl ether ethylene cyclic carbonate -butyrolactone Amides 2,5-hexanedione 6-hexanolactone formamide 1,2-propanediol cyclic N,N-dimethyl acetamide carbonate 2-chloroacetamide oxohexamethylenimine Uea 2,3-butanedione 1,1,3,3-tetra methyl urea ethylene trithiocarbonate acrylamide propiolactone cyanamide 2-piperidone N,N'-bis(2-cyanoethyl) n-butyl carbonate formamide 2-cyanoacetamide 4,4,4-trifluoro-1,2thienyl-1,3-butanedione 2-furamide 24-pentanedione N-2 hydroxyethylformamide dipropylcarbonate N-ethyl p-toluene sulfonamide 2,4-pentanedione N-ethyl-o-toluene sulfonamide Nitriles N-2-hydroxyethylacetamide ethylene dinitrile tetrace methane sulfonamide tonitrile pimelonitrile . N-(2-methoxy ethyl)acetamide 3,3-thiodipropionitrile N,N'-methylene bis acrylamide 3,3-oxydipropionitrile N-ethyl formamide phenylacetonitrile hydracrylonitrile o-methoxybenzaldehyde imino diacetonitrile tetrahydroionone pmethoxyphenyl acetonitrile pyridazine iodide glutaronitrile decahydronapthalene succinonitrile diphenyl methane picolino nitrile durene nicotinonitrile benzonitrile d-limonene ethylcyanoacetate turpentine 4-chloro-3-hydroxybutyroni mineral oil trile dichlorophenyl trichlorosilane 3,3'-(2,2-Bis(2-cyano ethoxy methyl)-trimethylane octadecyltrichlorosilane dioxyl diproplenitrile diphenyl dichlorosilane Aldehydes, ketones, thiones, epibromohydrin miscellaneous compounds 1,1,2,2-tetrabromoethane 2'-hydroxyacetophenone 1,2,3,4-tetrahydronapthalene salicylalehyde tetrachloroethane fenchone 1,2,4-trichlorobenzene 4-anisaldehyde indene o-chlorobenzaldehyde pyrrolidinone isophorone 1-butyl-2-pyrrolidinone cyclohexanone 1-cyclohexyl-2-pyrrolidinone 2-piperidone Basic Compounds - and amines, hydroxides, oxides, sulfides, 2-furaldehyde hydrates, alcoholates, hetero 1-methyl-2-pyrrolidinone cyclics 2,6-dimethyl-4-heptanone iodine chloride-iodine systems p-cymene sulfur chloride-iodine systems o-dichlorobenzene benzyltrimethylammoniumhydroxide o-nitrotoluene betaine hydrate nitrobenzene isosafrole choline 3-methyl piperazine n-ethyl morpholine 4-methylpiperidine 2,6-dimethyl moropholine 4-methyl thiazole hexamethylene tetra-amine 2-methylthiazole 2-picoline-1-oxide 2-methyl tetrahydrofuran tetramethylammoniumhydroxide tetrahydrothiazole tetrabutylammonium hydroxide 1,4 oxathiane 4,146,454 19 20 TABLE II-continued tetramethyl guanidine 2-amino-1,3-bis(2-ethylhexyl)-1,2,3-azimidobenzene 3-ethyl-4-methylpyridine 5-methyl hydropyrimidine 5-ethyl-2-methylpyridine 3,5lutidine hexamethylene imine Acidic Media tetrahydrothiophene 1,1- methane sulfonc acid dioxide dimethyl sulfoxide dichloroacetic acid imino-bis-propylamine mercaptoacetic acid triethylene tetramine 3-mercaptopropionic acid butyraldoxime propionic anhydride 2-amino-4-methyl thiazole lactic acid N-propyl sulfoxide 2-chloropropionic acid N-butyl sulfoxide propionic acid alpha picoline sulfoacetic acid beta picoline trichloroacetic acid quinoline (ethylene dinitrol) tetra acetic acid trimethylacetic acid aminoethyl1,2-diazine piperazine picric acid 2-methyl-5-ethyl pyridine camphoric acid N-hydroxyethyle piperidine hexanoic acid 3-ethyl-4-methyl pyridine picramic acid 4-ethyl pyridine cyanuric acid 2,4lutidine picrolinic acid 2,6-dimethyl pyridine-n-oxide Lewis acids Lewis bases 2,2'2' nitrilo triethanol p-toluenesulfonic acid hydrochloride trifluoroacetic acid semicarbazide hydrochloride amino imino methane sulfonic acid ammonium formate amino ethane thiol sulfuric acid ammonium thiocyanate 2-amino ethyl hydrogen amolitum nitrate sulfate perchloric acid ammonium bromide sulfamic acid lithium bromide phosphoric acid lithium iodide sulfuric acid morpholine oleate nitric acid lithium nitrate Salts lithium hydroxide betaine hydrochloride cesium acetate choline chloride cesium chloride hydroxylammonium acetate cesium carbonate hexadecyltrimethyl ammonium cesium salicylate bromide potassium iodide quanidine nitrate poly vinyl benzyl trimethyl tetrabutyl ammonium iodide ammonium chloride tetra ethylammonium bromide hydroxylammonium acid sulfate tetra methyl ammonium bromide Lewis salts 1,1,1 trimethyl hydrazonium iodide acetylcholine bromide acetylcholine iodide aminoguanidine nitrate 6-amino-3-indazolinone dihydrochloride cyanuric chloride guanidine acetate guanidine hydrochloride amino guanidine bicarbonate Formulation of the EMP media is fundamental. It has 50 Components used in EMP media formulation should been found that compounds or mixtures with a large have a number of characteristics if they are to be maxi liquidity range are particularly suited for use in EMP, mally useful. Water and solvent miscibility are often especially those liquids with a glassy or vitreous struc desired, and is general solvent action, availability, and ture. These compounds or mixtures apparently have an thermal, shelf, chemical and electrical stability. Supe inherent structure which facilitates regulation of proton rior solvent activity is not always desired. It is feasible donor/acceptor properties and electron charge transfer, 55 to limit or cause differential movement when two or as well as providing the advantage of low evaporation. more transportable chemical species are present in the It is sometimes practical to use high boiling point liquids media by using media components which are poor sol because the practice of EMP at or above higher thresh vents for one or more species. Below is a list of addi old currents does generate some heat. Media with tional compounds useful for their solvent action or their higher or lower melting and boiling components may be 60 ability to mediate such properties in other materials. used for special applications. Also included and tracer agents which will be discussed more fully hereinafter. TABLE III HYDROXY, ETHER COMPOUNDS 1,2,4-Butanetrio 2-(Ethyl thio)ethanol O-Tertibutyl phenol Ethynyl cyclohexanol 2,2-Bis(hydroxy methyl) Ethynyl cycloheptanol propionic acid Ethynyl cyclooctanol 4,146,454 21 22 TABLE III-continued 2,3-Butanediol Glycidol 1,4-Butanediol diglycidyl Guaiacol ether Hydroxyacetone1,2,6-Hexanetriol 2-Butene-1,4-diol2-(n-Butylamino)-ethanol 3-Hydroxy camphor Butylhydroxytoluene 2-Hydroxy cyclodecanone 2-Butyne-1,4-diol 2-Hydroxyethyl ether Cetyl Alcohol 2-Hydroxyethyl hydrazine Chloral N-Hydroxyethyl morpholine Cyanoethyl sucrose 2-(Hydroxy methyl)-2-ethyl-1, Dichlorotriethylene glycol 3-rpoapnediol ihydroxyacetone 1-(Hydroxy methyl)-5, 2,2-Diethyl-1,3-propanediol 5-dimethylhydantoin 2,5-Dihydroxy methyl pyrrole 2-Hydroxyethyl methacrylate 1,3-Dimercapto-2-propanol 1-(B-Hydroxyethyl(2-methyl 2,3-Dimercapto-1-propanol 2-imidazoline Dimethoxy tetra ethylene 4-Hydroxy-3-methyl-2-butanone glycol 2-Hydroxy-3-methyl cyclopenten-1- 2,3-Dimethyl-2,3- onehydrate butanediol 3-Hydroxy-2-methyl-4-pyrone Dimethylol propionic 5-Hydroxy oxindole acid 3-Hydroxy piperidone 2,2'-Dithiodiethanol 2-Hydroxypyridine Dodecyl alcohol 5-Hydroxy-4-octanone polyoxyethylene ether Iodopropylidene glycerol O-Ethyl phenol N-Methylol-2-pyrrolidone Anilino ethanol Diethanol sulfide Amylether aa-Dimethyl phenethyl alcohol Benzene thiol 2,4-Dimethyl phenol Benzyl alcohol 2,6-Dimethyl phenol Benzyl butyl ether 4,6-Dinitro-o-cresol N-Benzyl ethyl ether 2,4-Dinitro phenol 2-Benzyl oxythanol 2,6-Dinitro thymol 4-Bromodiphenyl ether 2,3-P-Dioxanediol N-Butyl phenyl ether Diphenyl ether N-Butyl diethanolamine 2,6-Di-tert-butyl-p-cresol 1-Chlor ethyl cellosolve 2,6-Di-tert-butyl phenol 1-Chloro-3-pentanol 2,4-Di-tert-pentyl phenol 4-Chloro cyclohexanol 6,6-Dimethyl bicyclo 3,1,1 6-Chloro-1-hexanol hept-2-ene-2-ethanol Dodecyl alcohol O,M,P-CresolsO.M.P-Chlorophenols P-Dodecyl phenol 6-Chloro thymol 1-Dodecane thiol 2-Cyano ethanol 1,2-Ethane dithiol Cinnamyl alcohol Ethane thiol Cedro 1-Ethoxy naphthalene Cyclohexanol O-Ethoxy phenol 1,4-Cyclohexane di Glycerol dimethyl ether methanol 3-Hydroxy propionitrile Decanediol 3-Hydroxy propylene oxide 2,3-Dibromo-1-propanol 1,6-Hexanediol 1,3-Dichloro-2-propanol Hexyl cellosolve 2,3-Dichloro-1-propanol D-Methoxyphenol 2,4-Dichlorophenol DL-a-Methylbenzyl alcohol 1,3-Dichloro-2-methyl-2- 5-Methyl-2-isopropyl phenol propanol 2-Methyl-1,2-3-propanetriol 2-Imidazoline-1-ethanol Polymethyl alkyl siloxanes 5-indanol Pyrrole-2-ethanol 2-(Iso propylthio)ethanol Pyrrole-2-methanol Lanolin alcohols, acetylated Stearyl alcohol 5-Methyl-1,3-dioxane-5- 2,5-Tetra hydrofurandimethanol methanol 1,2,3,4-Tetra hydro-2-napthol 2-Nitro-2-ethyl-1, Tetra hydro pyran-2-methanol 3-propanediol Tetrahydro-2)2)5-trimethyl-5- 2-Nitro-2-methyl-1-propanol cinyl furfuryl alcohol O-Nitro anisole Tetrahydropyran-2-methanol O-Nitro phenol 2,2,4,4-Tetramethyl-1,3- 2-Methyl-1-phenol-3-butyne-1, cyclobutanedi 2-diol Tetra ethylene glycol M-Nitrobenzyl alcohol 2-Thenyl alcohol 2-Nitroethanol Thiobenzyl alcohol 1,5-Pentanediol 2,2'-Thiodiethane thiol Pentaerythritol 2,2-Thiodiethane thiol P-Pentoxyphenol Triethylene glycol dimethyl ether Phenethyl alcohol 1,1,1-Trichloro-2-propanol Sec. Phenethyl alcohol 1,1,1-Trichloro-2-methyl-2- 1-Phenyl-1,2-ethanediol propanol (& hydrate) Polyethoxyethylated(1-20) 1,1,-Trimethylol ethane oleyl alcohols Trimethylolpropane Polyethoxylated lanolin(5+) Tris(hydroxy methyl)nitromethane alcohols Toluene-3,4-dithiol Polyethoxylated (75) lanolin Aldol Polyethoxylated (9) acetyl l-Amino-2-propanol ianolin alcohol 3-Amino-2-propanol P-butoxy phenol 3-Amino-2-butanol Polyclycols 2-amino thiophenol 2-Methyl-2,4-pentanediol O,P-Toluenethiol 2-Methyl cyclohexanol 3-Cyclohexene-1-methanol 3-Methyl cyclohexanol 3-Cyclohexene-1-dimethanol 4-Methyl cyclohexanol 3-Nitro-2-butanol 2-Methyl-1-phenyl propanol-l 2-Nitroethanol 2-Methyl-1-phenylpropanol-2 2-Nitro-1-propanol P-(methyl thio)phenol 2-Nitro diphenyl ether AMIDES, IMIDES 4,146,454 23 TABLE III-continued -Octanol 1,2,3-Propanetriol 4-Acetamino-2,26,6-tetramethyl piperidino-1-oxyl 1-Phenyl-1-propanol 2-Acetamido-3-butanone 3-Phenyl-1-propanol 4-Acetamidobutyric acid 2,2,4,4-Tetra methyl-1, 4-Acetamidothiophenol 3-cyclobutanediol 2-Acetamido thiazole P-1,1,3,3)-Tetra methyl 2-Acetoacetamido-4-methyl butyl phenol thiazole Thio phenol Adipamide M-Thio cresol N-Allyl methacrylamide Crown ethers 6-Amino nicotinamide Trimethylol amino ethane Anthranilamide 1-(2-Hydroxyethyl piperozine Azodiacarbonamide P-Hexyl phenol N-Bromoacetamide P-Hexyl oxyphenol 2-Bromo-2-ethyl Iso valeramide O-Phenyl phenol N,n-Butul acrylamide 2,4,5-Trichlorophenol N-Butyramide 2,4,6-Trichlorophenol Iso-butyramide 2,2,2-Trichlor-i-ethoxy Chloral formamide ethanol Cinnamamide 2-Vinyl oxyethyl ether Diacetamide 2,4,6-Trinitroresorcinol N,N'-Diallyl tartardiamide N,N-Dibutyl formamide Fumaramide 2,2-Dichloroacetamide 1-Glutamide N,N'-Dicyclohexyl carbo Glutaramide diimide Heptamide Diethyl formamido malonate N,N-Hexamethylene formamide N,N-Diethyl Tso nico Hexamethyl phosphorour triamide tinamide 2,2,2-Trichloroacetamide N,N-Diethyl nicotinamide N-Hydroxyacetamide N,N-Diethyl nipecotamide 2-Hydroxy ethoxyacetamide N,N-Diethyl-1-piperazine N-(2-Hydroxyethyl)-phthalimide carboxamide N-(Hydroxy methyl)-nicotinamide N,N-Dimethyl acetoacetamide N-Hydroxy succinimide N,N-Dimethyl nicotinamide 5-Hydroxy valeramide 3,3-Dimethylglutaramide Iodoacetamide 2,4-Dihydroxybenzamide Iso-nicotinamide N,N'-Dimethyl oxamide Iso-nipecotamide 3,5-Dinitrobenzamide N-Isopropyl acrylamide 2,3-Epoxy-2-ethyl N-Iso propyl salicylamide hexanamide N-Lauryl methacrylamide N-Ethyl acetamide Maleamic acid Ethyl acetamidoacetate Maleimide N-Ethyl acrylamide Maleondiamide N-Ethyl maleamic acid N-Methyl acetamide 3-Ethyl-3-Methyl N-Methyl acrylamide glutaramide N-Methyl maleimide N-Ethyl methacrylamide 2-Methyl malonamide N-Ethyl nicotinamide N-Methyl nicotinamide N-Ethyl propionamide N-Methyl propionamide Ethyl oxamate N-Methyl 2,2,2-Trifluoroacetamide Fluoroacetamide Methyl-2,2,2-Trichloroacetamide P-Nitrobenzamide 1-Naphthaleneacetamide Oxamic acid 4-Acetamido-2,2,6,6-tetra Oxamide methyl piperidine a-Phenylbutyramide N-Butylacetamide Phenyl formamide tert-Butyl carbazate N-Phenyl succinimide Diacetone acrylamide Phthalamide N,N-Diallyl formamide N-Polyoxyethylene fatty Dibutyl cyanamide acid amides N,N-Dibutyl propionamide Propionamide N,N-Diethyl acetamide Pyrazinamide Diethyl acetamido malonate Stearamide N,N-Diethylbutyramide Succinimide N,N-Diethyl formamide Succinic diamide N,N-Diethyl propionamide Sulfabenzamide N,N-Diethyl-m-toluamide Sulfacetamide N,N-Dimethyl dodecanamide Sulfamide N,N-Dimethyl propionamide N-Sulfanyl stearamide N,N-Dimethyl thioacetamide N,N',N',N'-Tetra ethyl N,N-Dimethyl thioformamide phthalamide N,N-Dimethyl valeramide N,N,N',N'-Tetra ethyl 3,5-Dinitro-o-toluamide fumarimide N,N-Diphenyl acetamide N,N,N',N'-Tetra methyl N,N-Dipropyl acetamide carbamide N,N-Dipropyl decanamide Thiobenzamide N,N-Dipropyl propionamide Thionicotinamide N-Ethyl maleimide OP-Toluamide Ethyl methyl carbamate 2,2,2-Trifluoroacetamide Hexanamide Trimethylacetamide Hexaethyl phosphorus triamide Valeramide 2-Hydroxyethyl carbamate N-2-(Hydroxyethyl) 2-Chloroethyl trichlor acetate succinimide 2-Chlor ethyl chloro acetate 2-Furamide 69-Diamino-2-ethoxy Lactamide acridine lactate N-Methyl benzamide Diisopropyl adipate N-Methyl diacetamide Dimethyl methyl phosphonate M-Methyl-N-1-naphthyl 2-Diisopropylaminoethyl-p- acetamide amino benzoate N-Methyl-2-phenyl acetamide Di iso-butyl carbonate N,N,N',N'-Tetra methyl Dibutyl sulfite glycinamide Dibutyl (--) - tartrate N,2,2-Trimethyl propionamide Dimethyl maleate 4,146,454 25 26 TABLE III-continued 2,2,5,5-Tetra methyl-3- Dimethyl malonate pyrrolin-1-gloxy-3- Diethyl oxalate carboxamide Dibutyl oxalate l-Naththaleneacetamide Diethyl adipate Phenyl carbonimide Dipropyl adipate Acetamidine acetate Dibutyl adipate P-Acetamido benzaldehyde Diethyl sebacate P-Acetamido benzoic acid Di iso-butyl adipate N-2-(Acetamido)-imino Di-N-butyl sebacate diacetic acid Dimethyl phosphite Ethyl trichloro acetate ESTHERS, CARBONATES Ethylene(mono) thio carbonate AllylideneBis(2-Ethylhexyl)sebacate Diacetate Ethyl-2-pyridine carboxylate Bis(2-Ethoxyethyl) sebacate Ethyl anthranilate Bis(2-Ethylhexyl) phthalate Ethyl acetoacetate N-Butyl oleate Ethyl benzoate Butyl nitrite 2-Ethylhexyl acetate Glucose-1-phosphate Ethyl dichloroacetate Glycol diformate Trilauryl phosphite Isobutyl carbonate Trimethyl-3,3,3'-Trilauryl trithiphosphite Iso-pentyl nitrite nitrilotripropionate Iso-propyl salicylate Trimethyl phosphate Methylcyanoacetate Triethyl orthopropionate Methyl cinnamate Triethyl phosphite Methyl decanoate Tri Isopropyl phosphite Methyl myristate Tributylborate Methyl octanoate Methyl palmitate Tri(2-Tolyl)phosphite Methyl salicylate Tetrahydrofurfuryl propionate Methyl stearate KETONES, ALDEHYDES Monostearin 2-Acetyl cyclohexanone Monolein P-Acetaldehyde Methyl abietate Anisole Methyl acetoacetate P-Butyraldehyde Methylbenzoate Butyrophenone Methyl trichlor acetate P-Chlorophenetole N-Octyl nitrate Cinnemaldehyde Phenyl carbonate 1,2-Cyclohexanedione Polyoxyethylene stearate 1,2-Cyclodecanedione Isopropyl salicylate 3-Cyclohexene-1-carboxaldehyde 1,3-Dichloro-2-propanone PhenylSEP acetate nitrate Decanone Propylbenzoate 2,5-Dimethyl cyclohexanone Tetrahydrofurfuryl nicotinate 3,5-Dimethyl-5-ethyl-2,4-dione Tetryhydrofurfuryl acetate N-Formyl hexamethyleneimine Tetra nitro methane Hexachloroacetone 2,2,2-trichloro ethyl carbamate 2,4-midozolidine dione 2-Inidozolidone Pyrrole-2-carbaldehyde Indole-3-cyclohexanone Thiophene-2-carbaldehyde L-Methone Tribromoacetaldehyde 4-Methoxyacetophenone Veratraldehyde Methyl benzophenone O,P-Vanillin O-Methyl anisole O-Phthaldialdehyde 4-Methyl acetophenone 1-Phenyl-3-pyrazolisinone a-Methyl cinnamaldehyde 2-Heptanone 2-Methyl piperazine-N, N'-dicarboxaldehyde Pentaerythritol diformal N-Methyl pyrrole Methyl-2-thienyl ketone carboxaldehyde Cyclododecanone N-Morpholino carboxaldehyde Azacyclotridecanone Nicotinaldehyde HETEROCYCLICS, ACIDS, AMINES 5-Nitro salicylaldehyde (& SALTS), MISCELLANEOUS Nitroso salicylaldehyde SUBSTANCES 2-Octanone. N-Acetyl morpholine 1-Phenyl-2-propanone 2-Acetyl pyrrole Phenetole 2-Acetyl thiophene Picolinoaldehyde Acridan 1-Piperazine carboxaldehyde Acridine 1,4-Piperazine Acridine orange dicarboxaldehyde Acridine yellow N-Piperidino carboxaldehyde Acriflavine Piperonal Allyl thiourea Propiophenone 1-Allyl pyrrole 2-Pyridone 2-Allyl pyrrole 4-Pyridone Amino acids Pyridine-2-carbaldehyde 9-Aminoacridine Pyridine-3-carbaldehyde 3-Amino acridine O-Aminophthalhydrazide Dimethyl acid pyrosphosphate Benzothiazole 2,5-Dihydrothiophene 1,1- dioxide N,N'Bis (3-amino propyl)- piperazine 2,3-Dihydro-4-pyran Bis(2-Ethylhexyl) 2,4-Dimethyl-3-ethyl pyrrole orthophosphoric acid 2,3-Dimethyl-4-ethyl pyrrole 2,2-Bis (ethyl sulfonyl) 2,5-Dimethyl pyrrole butane 3,4-Dimethyl-5-sulfanilamido 1,8 Bis(dimethylamino)- iso oxazole, salts naphthalene Di Phenyl sulfide Butyl sulfone Diisopropanolamine Bis(2-ethylhexyl) Dichloropropionic acid hydrogen phosphate N-Nitroso diethylamine Butyl disulfide 1-Nitrosopiperidine 4,146,454 27 28 TABLE III-continued Tert-butyl disulfide Dibutylbutylphospho 9-Chloroacridine a-Glucose-1-phosphoric acid 4-Chloromethyl-1-acridine Gluconic acid 2-Chloropyridine Guar Gum 4-Chloropyridine Indole A,B-Cyclopentamethylene Imidazole Iminodiacetic acid tetrazole Hexamethylene imine 3,6-Diamino1,8-Diamino-p-methane acridine 3,5-Lutidine-N-oxide 1,2-Diazole 2-Lactoyl oxypropanoic acid Dihydroacridine Lithium acetate 1,2-Dihydro-3,6- Lithium perchlorate pyridazinedione i-Methyl imidazole 2,3-dihydrofuran 2-(Methyl thio)benzothiazole 3,4-Dihydro-1(2H)- 2-Methyl glutaronitrile naphthalenone Methyl isobutyl ketoxime Methyl phenyl sulfide Pyrimidine 1-Methyl-1-phenyl hydrazine Pyrrole 3-Methylsulfolane Quinoxaline N-Methyl pyrrole Safrole Nepatolactone Stearic acid Nitrocyclohexane Trimethyl sulfoxonium iodide O-Nitrophenol 1,2,3-Trimethyl benzene 2-Nitropyrrole 1,2-Epoxycyclododecane N-(3-Amino propyl)-2- O-Nitroanisole pyrrolidinone 2-Nitrofuran,i-Nitrosopiperidine 3-Nitrofuran N-(3-Amino propyl)-morpholine Oxypolygelatin Acetonaphthane Pantoic acid-a-lactone 4-(2-Amino ethyl)morpholine 1,5-Pentamethylene N-(3-Amino propyl)-morpholine tetrazole N-Butylaniline O-Phenetidine Butyl sulfide Phenyl hydrazine Benzylamine Phenyl mercuric borate Benzedrine P-Phenetidine 2-Benzyl pyridine 4-(3-Phenyl propyl)- 1-Bromonaphthalene pyridine Butylbenzene Phenyl phosphonous 1-Bromo-2-iodobenzene dichloridate 1-Bromo-3-iodobenzene Phenyl phosphoro dichloridate Butyl nitrite Phenyl phosphone thioic Cyclododecane dichloride 1,5,9-Cyclododecatriene Phenyl phosphoric dichloride Cyclododecene Piperine 1,2-Cyclohexane dicarboxylic Pyridine-1-oxide anhydride Pyridazine Cedrene O-Diethyl benzene 1-ghloronaphthalene 3,4-Dimethylpyridine 2-Chloroquinoline Dibutylamine 3-Cyclohexapropionic acid O-Diethylbenzene Caprylic acid 1-Ethylnaphthalene 1-Chloro octane 2-Ethylnaphthalene Chloropicrin 3-Tehylrhodanine Caproic acid 1-Ethylpyrrole O-Chloroaniline Ethyldiethanolamine Cumene2,4-Dichloropyrimidine O-Ethyltoluene 3,6-Dichloropyridazine Fluorosulfuric acid-antimony 3,7-Dichloroquinoline pentafluoride 2,5-Dihydro-2,5-dimethoxy Isopentyl nitrite furan Heptanoic acid N,N-Dimethyl cyclohexylamine Lactonitrile 1,4-Dimethyl piperizine Lithium oleate, palmitate, stearate 1,4-Dinitroso piperazine O-Iodotoluene 2,3-Dichlorodioxane1,5-Dichloropentane P-Isopropyltoluene Dibenzylamine 1-Iodonaphthalene N,N-Dibutyl aniline 1-Iodo octane Dipentylamine lso pentyl nitrite 1,3-Dioxepane 2-Methylbenzothiazole 2-Methyl benzoxazole 2-(1,3-Dioxolane-2-yl)1,3-Dioxolane 1,2-Methylenedioxybenzene pyridine 1-Methyl naphthalene 4,4'-Dithiomorpholine 2-Methyl naphthalene 3,4-Dimethyl furazan 2-Methyl-2-nitropropane Di isoamglamine N-Methyl-N-nitrosoaniline Dibutyl amine Methoxyacetic acid 4-Methyl morpholine Aluminum lactate N-Methyl-P-nitroaniline, Amino phosphonic acids O-nitroaniline Bismuth ethyl camphorate 2-Methyl quinoline Calcium carbamate 2-Methyl pyridine Calcium borogluconate 3-Methylpyridine Calcium palmitate 4-Methyldioxolane Calcium stearate Methyl urethane Calcium galactogluconate bromide a-Methylstyrene Circumin 1-Nitropropane Cinnamonitrile 2-Nitropropane O-Diacetylbenzene 1-Nitrobutane Decahydroquinoline i-Nitrohexane 1,4-Dichlor-2-nitro benzene Nitro trichloro methane 1,2-Dichloro-4-nitrobenzene N-Octyl nitrate 1,1-Diethyl urea 4-Phenyl-1,3-dioxane Dimethyl phosphite 3-Propyl rhodanine Diphenyl selenide Propyl disulfide Diphenylimidazalon-sulfonated 4,146,454 30 TABLE III-continued Propyl sulfide Flourescamine Propyl sulfone N-lodoacetyl-N'-(5-sulfo-1- Piperidine naphthyl)-ethylene diamine Valeric acid N-Iodoacetyl-N'-(8-sulfo-1- Trimethylene sulfide naphthyl)-ethylene diamine Lutidines MISCELLANEOUS SUBSTANCES 2-Methyl-2-thiazoline Acridine red O-Methyl toluidine Acridine iso thiocyanate Metrizaminde Acriflavine Nile Blue Aesculin Neutral red Allantoin Neutral violet Phenyl ethylene oxide 2,3,4,5-Tetramethyl pyrrole 1-Phenyl propane N,N',N',N'-Tetramethyl-1, Primuline 8-naphthalene diamine 1,3-Propanesultone 2,3,5,6-Tetramethyl piperazine Isopropyl benzene 2,2,4,4-Tetramethyl-1,3-cyclo N-Propyl nitrate butadiamine 1,4-Pyrone 1,2,3,4-Tetramethyl benzene Pyruvic acid 3,3',5,5'-Tetramethyl benzidine Safrainin Tetranitro methane Sulfonyldiacetic acid Tetrocyanoethylene Sulfuriodide Thiamorpholine Tetrabutyl ammonium Thiolactic acid petchlorate 3,3'-Thiodipropionic acid Tetrabutyl ammonium Thiophthene fluoroborate 1,4-Thioxane Tetracutyl ammonium Thioflavine bromide OM,P-Toluidine Tetraethyl ammonium Triazio benzene perchlorate Tri-N-butyl amine Tetraethyl thiuram sulfide Tri isobutyl amine Tetraethyl ortho silicate Tri-N-butyl phosphine oxide Tetraethyl ortho titanate Tributyl phosphine 1,1,3,3-Tetraethyl urea 3,5,5-Trimethyl-2,4-oxazolidine Tetra isopropyl ortho titanate dione 1,1,3,3-Tetraethoxy propane Tetraethyl tin Trimethyl sulfonium iodide Tetrahydrofurfuryl oxy Trimethyl sulfoxonium iodide tetrahydropyram Trimethyl amine N-oxide, hydrate 1,2,3,4-Tetrahydro 2,4,6-Trimethyl1,3,5-Trinitrobenzene pyridine isoquinoline Trichloromethyl phosphonic acid Trioctylphosphine oxide Trioctyl phosphine Tri-N-pentyl amine Vasoflavin Vinyl carbazoles Zinc oleate

As part of the methodology which may be used to Often even partial miscibility with water is sufficient to categorize the materials such as those listed herein they indicate the range of activity or character to be ex may be titrated with distilled water and their conductiv 40 pected. Further, these studies are extended by titration ities obtained. The dilution/conductivity curve so ob against materials other than water. Thus, for example tained indicates the rate of change of conductivity with dichloracetic acid, formamide and thiodiethylene gly dilution as well as the diminishing point or plateau lev col were used. These then represent a different solvent els of conductivity achieved within reasonable dilution miscibility capability and profile. Of these agents, the means which helps characterize the materials as to the 45 formamide has a very high dielectric constant and several categories discussed herein, such as very active greater conductivity than water, whereas the thiodieth solvents, active solvents, etc. The following data illus ylene glycol's conductivity was in the range of the trates the application of this technique (resistances are water used and also achieved the level of conductivity given in milliona of ohms). The very low plateau of of the water when a drop of water was added; that is, resistance at the indicated dilution levels establishes that upon only slight dilution with the water. The conduc dichloroacetic acid and mercaptoacetic acid are in the tivity changes so produced by dilution with nonaqueous category of very active media. The somewhat higher materials were further characterized by observing plateau of ethylene carbonate and 2,5-hexanedione changes in plateau levels so produced by addition of a place them in the category of active media. By such a minor quantity of secondary solvents which may be method a convenient rating scale can be established for 55 water. This helps to relate the influence of secondary evaluation of different media. This technique assists in solvents such as the active or very active type (or inert tailoring media to a desired conductivity value by ob type for suppressant activity) to the conductivity pro servation of resistance values at different levels of dilu file. Such effects are variable or characteristic for the tion. diluted agents to which the secondary diluent is added.

NITIAL RESISTANCE RESISTANCE RESISTANCE, WTH.05 m. WTH 1 m. SAMPLE 0.3 ml. WATERADDED WATER ADOED dichloroacetic acid 100 0.042 0.00 mercaptoacetic acid 0.050 0.004 ethylene carbonate 0.2 0.20 0.06S 2,5-hexanedione 7 2.2 0.060 4,146,454 3. , 32 Further, the conductivity titration curves may be stud propanediol cyclic carbonate, 5 ml. propylene glycol, 2 ied with a particular conductivity-valued diluent which ml. N-methylacetamide and 0.4 ml. tetrahydrofurfuryl may already be an ionized or higher conductivity sys alcohol allows the resolution of rhodamine B and 6G of tem. For example, the dilution of hydroxy compounds examples 16 above in considerably less than the 3.6 cm. and ethers with fairly conductive aqueous ammonium 5 required in example 16. The utilization of resolution nitrate solution and acetic acid may be cited. The com improvement to shorten separation distances makes is parison was made where both latter systems had equiva possible to minimize diffusional effects. lent conductivities. Of the compounds 1,3-butane diol, It is possible to improve resolution generally accord 2,2-methoxy ethoxy ethanol, 2-oxydiethanol bis (2- ing to the following procedure. A suitable solvent is methoxyethyl) ether, sorbitol (40% aqueous solution) 10 found for the chemical species to be transported. The and sorbitol (57% aqueous solution) by volume, the nature of the chemical species to be transported is then dilution of the aforementioned aqueous conductive so analyzed in terms of its proton donor/acceptor proper lutions by the latter compounds generally shows a simi ties. The donor/acceptor properties of a number of lar decrease in conductivity over the titration range chemical species are catalogued in the literature. E.g., although certain definite curve shapes were derived. 15 V. Gutmann, Coordination Chemistry in Non-Aqueous Thus, the relative activity and suppressant profile of the Solutions (1968). A component should then be added to various diluants became evident. With this technique, the media which will interact in a proton donor/accep the substantial difference with bis (2-methoxy ethyl) tor interaction with the chemical species. In many in ether is readily evident. Also differences were noted in stances the proton donor?/acceptor properties of chemi the effects of aqueous sorbitol at various concentrations, 20 cal species are not catalogued, or are complex. In such as compared to the nonaqueous materials, upon the cases it is possible to determine the type of media com ionized ammonium nitrate solution which effects were ponents that will improve resolution by testing the sys otherwise somewhat less pronounced than upon a dilute tem through the simple technique of addition of a very acetic acid solution. Further, the various systems may strong proton donor to one sample and then a very be studied as they affect equilibria characteristics, ioni 25 strong proton acceptor to another. If the strong donor zation and/or formation data for the materials of inter increases the mobility (rate of movement) of the com estand at various pH's. A large compendium or library pound, donors of varying strength are then tested to of data may be prepared for these various possibilities in determine which provides the greatest improvement in order to achieve a lessened empirical basis for condi mobility and resolution. An analogous procedure is tions of system selection for use. As a result of this 30 followed if the strong proton acceptor increases the invention an already established broad table is given of mobility rate of the chemical species. The addition of a basic solvent systems from which future screening can component which can interact with the chemical spe be made to develop media for use with particular spe cies to be transported by proton donor/acceptor inter C16S. As illustrated by the above examples and the lists of 35 action seems to facilitate initial mobilization of the chemicals, the process of this invention comprises sepa chemical species. The dielectric constant of the media is rating or mobilizing chemical species which are conve then adjusted if necessary to a moderately high level. It niently on a support such as filter paper in a medium of may also be necessary to correct for electrical instability low conductivity across which a high voltage is im of the media by addition of a compensating component pressed. The media-base comprises one or more com 40 as detailed above. pounds, for example, inorganic or organic compounds As an additional aspect of this invention it has been such as glycols, ethers, esters, diones, lactones, amides, determined that improved tailoring of the semiconduc nitriles, alcohols and water. An agent may be added to tive media also permits, for certain chemical species, the medium to adjust its conductivity and such agent exhibition of an EMP resonse observable with the un may be selected from the group consisting of water, 45 aided eye at relatively low voltages and reduced power acids, bases and salts. The voltage used in the process is levels, as compared to the high voltage, high power within the range of about 50 to 25,000 volts/cm. At processes described above. Voltages below 50 v/cm very high voltages, and particularly with volatile or and even less than 20V/cm on conventional support gaseous substances, cooling may be required. The pre media have been utilized. For example, one can achieve ferred range is about 200 to 3,000 volts/cm, and in this 50 EMP transport at power levels as low as 3x10°W. to range the process can be carried out without external 1.7x10TW. with voltages of 2 to 4 volts at 1.5 to 4.2 cooling. The conductivity of the medium is preferably u.A. over several centimeters of No. 1 Whatman filter adjusted to provide a current density in the range of paper. This represents EMP operation at potentials of about from 0.2 to 100 microamps/sq. cm. based on the several millivolts per centimeter attenths of microwatts area of, for example, filter paper as a substrate. The 55 per square centimeter. The limit on low voltage EMP is preferred range is 1.4 to 54 microamps/sq.cm. For bulk the level at which electrical diffusivity comes into play. work and with external cooling, current densities above It has also been found that certain agents will act to 100 microamps/sq. cm. can be used. TThe transport reduce the threshold current of a chemical species. medium, after appropriate adjustment of its conductiv A media system is modified to allow low voltage ity, is subjected to a sufficiently high voltage at a low 60 EMP response and to reduce threshold current in much current level (at about the threshold level) to induce the same manner as it is modified for resolution im separation of the chemical species therein at a rate of provement. Specifically, iniciators and mobilizers are about 1 cm/sec. to about 0.25 cm/min. In the above added. Initiators are compounds which act to reduce examples, at the conditions indicated, no external cool the threshold current of a given chemical species, and ing was required. 65 mobilizers are compounds which act to increase the Refinement of media formulation techniques can lead mobility (transport rate) of a given chemical species. to resolution improvement in the separation of given There is some overlap between the classes of com components by EMP. For example, the media of 5 ml. pounds useful as initiators and those useful as mobiliz 4,146,454 33 34 ers, that is, some compounds will act both as initiators formulation of semiconductive media may be effected and as mobilizers. within a living organism to control or study chemical In general, materials which will interact on a proton substances in physiologically functional systems. donor/acceptor level with the chemical species to be The voltage necessary to the EMP process may be transported and high dielectric constant materials are supplied by potential differences existing naturally in an useful as initiators and mobilizers. Examples of com organism and merely applied to the appropriate site, or pounds which are often useful both as initiators and may be imposed from an outside source. mobilizers are N-methylacetamide and salicylaldehyde. It is well known and recognized in the prior art that With the use of initiators, threshold currents may be potential differences exist within living organisms natu adjusted as low as 0.2 to 0.002 LA/cm, and EMP may 10 rally. Also, in connection with the experimentation be carried out at these currents at slower but still effec leading up to the present invention, it was found that a tive mobility rates with voltages as low as 0.05 to voltage reading on the order of tenths of volts or milli 10v/cm. The voltage level of 0.05 v/cm represented a volts with a current of microamps or slightly less was practical minimum during experimentation because generated across the phase boundary between two im voltage effects on this order inherent to the system were 15 miscible or partially immiscible liquids in certain in encountered. Overall, considering both high voltage stances. Not all phase boundaries produced this junc and low voltage EMP, the EMP voltage range may be tion effect; for liquids, partial solubility in each other 0.05 to 25,000 v/cm, with power levels as low as seems to correlate with the effect to some extent. The 1.2x10-9 to 5x 10-5W/cm2. junction effect may be modified by use of a permeable The following examples illustrate the manner in 20 membrane between the phases. Propanediolcyclic car which media, suitable for EMP transport according to bonate and water form different phases and exhibit this the criteria of semiconductivity and compatability with junction effect. It is believed that juxtaposition of liq chemical species described in connection with high uids in the cells of living organisms could give rise to a voltage EMP above, are modified with initiators to liquid junction effect providing sufficient voltage for reduce threshold current. 25 the effectuation of EMP. Such effects appear to be amenable to modification by EMP media formulation techniques. EXAMPLE SOLVENT FORMULAE The process of EMP media formulation may be car 22 7 ml. propylene glycol, 3 ml. diacetone alcohol (mobilizer, ried out in conjunction with an externally applied volt also enhances resolution), 2.2 30 age, as well as with one existing naturally within an mi. N-methylacetamide (high dielectric constant material, organism or portion thereof, to effect an EMP response. acts as initiator and mobilizer), Some evidence already exists, for example, of improved 1.3 ml. formamide (same). bone and other tissue healing or growth in the presence 23 21 ml. propanediolcyclic carbonate, 9 ml. methoxyethyl ethanol, 12 ml. of an applied voltage. See Lavine et al., Electric En tetrahydrofurfural alcohol, 3 drops 35 hancement of Bone Healing, 17 Science 1118 (March HNOs diluted 1:3 with water. 1972). Such effects could be enhanced by application of the desired chemical species. For example, the initiators The media of example 22 above has been used to or dielectric constant modifiers for transport of bio separate rhodamine dyes, and also to separate vitamin chemical species described herein could be applied to B12 and sodium riboflavin phosphate mixtures. facilitate or enhance an electrophysiological response The media of example 23 was used to separate rhoda such as transport or orientation of the appropriate mate mine B and 6G in less than 0.5 cm. The tetrahydrofurfu rials across a bone break. ral alcohol acted to embrace the mobilization of the More generally, given voltages and current levels compounds magnifying molecular differences. Without within living organisms, the procedure of media formu this component the two species showed almost equiva 45 lation of the present invention could be used to con lent motion over several centimeters. struct or modify within the organism appropriate semi As further examples, the media of example 23 can be conductive media for enhanced transport of physiologi altered to increase its conductivity by the dropwise cally significant chemical species. For example, EMP addition of conductivity, initiator or mobilizing agents media formulation techniques could be used to speed (A) to obtain the electrical values (B.) and power levels 50 reparative or other chemical species to injured portions (C) set forth in the table below. of the body. EMP media formulation might also be

(B) Electricl Values (C) Total EMP Power for EMP run (on Level in (A) Agent (4 x 1 cm Filter Paper) Microwatts Nitric acid (1:30 in water) 4V, 4.2ia 17 Ammonium bromide 10V, 1.ua 11 SEormamide in glycol) a 10V, 1.2a 12 N-Methyl Acetamide 20V, 2a 40 N-Methyl formamide . . . OV, 4.1a 40 Hexamethyl phosphoric triamide 10V, 3.5ua 35 The accomplishment of EMP at low voltages with accompanying, low power levels has important ramifi cations in that EMP under such conditions would be compatible with living organisms. Voltage, power and 65 useful with respect to the application or retention of threshold current levels appropriate for low voltage . drugs. EMP might be used to effect or control natural EMP exist in living organisms and consequently are processes on a humoral, intercellular, or even intracel clearly tolerated by them. Thus the EMP technique of lular level. 4,146,454 35 36 In the preparation of media within an organism, tox icity of the media components and other aspects of TABLE V-continued Other Representative Materials Suited for compatability with the physiological system would be Use in EMP Media in Biological Systems of key importance. Considerations of toxicity would isovaleramide include considerations of irritational, inhibiting and 5 kojic acid lactobionic acid citric acid denaturing characteristics. In selecting chemical materi linoleic acid als useful for in vivo EMP work, the particular tissue or lipoic acid tetrazole function to be modified must be taken into account. methylal acetamide Diethyl ethylphosphonate methylnicotinate N,N-diethyl iso-valeramide Even nitriles can find utility in such work, e.g, 2-cyano y-Methyl-af3 N,N-diethyl-m-toluamide ethanol is relatively non-toxic as well as non-irritating 10 N-methyl pyrrollidinone 2,2-dimethyl-1,3-dioxolane 1-methoxy-4-propenyl benzene 4-methanol and non-absorbing dermally. P-methoxybenzaldehyde 2,6-dimethyl-m-dioxan-4-ol As an example, if it were desired to utilize an agent P-methoxybenzyl alcohol acetate myristyl alcohol dimethylpolysiloxane intravenously in mammals (including humans) which is 3,4-(Methylene dioxy)benz 2,3-epoxy-2-ethylhexanamide well tolerated in fair concentrations, and which should aldehyde contribute amide but not urea character, either lactam 15 nicotinamide scorbate ethyl phenyl ether nicotinic acid monoethanol O-ethoxybenzamide ide or nicotinamide may be selected. For liquid or low amine propoxy (10-20) glucose 2-nitro-2-propyl-1,3- pentaerythritol chloral melting N-alkylamides or N,N-dialkyl amides, often of propanediol high to very high dielectric constant, analogues such as octanoic acid pentaerythritol tetraacetate N-ethyl nicotinamide or N,N-diethylnicotinamide may oleic acid 3-pentanone oils, natural 3-phenoxyl-1,2-propanediol be considered. A number of related compounds, e.g., 20 orotic acid henoxyacetic acid dibutyl formamide, N-cyclohexyl-formamide, diethyl N-(pantothenyl)-B-amino polyolyethylene-(20)-sorbitan nipecotamide, or N-(2-hydroxyethyl) lactamide, might ethanethiol monooleate Pantothenic acid phenylbutyramide, a be useful. cacoa butter 2-phenyl-2-hydroxy propion In addition to these examples, a listing of agents is E-caprolactam amide choline salts 2-phenyl-6- given for use in formulating buffers with minimal im 25 piperidinium salts theophylline & salts pairment of sensitive biological systems. Also, a brief poly(ethylene glycol)-p- O-thiocresol nonyl phenyl ether thujic acid listing is given of other representative agents suffi polyoxyethylene stearate tiglicamide ciently tolerated to be generally useful for biological polyvinyl alcohol tocopherols, tocols polyvinyl pyrrollidone 2,2,2-trichloroethanol work. Additional criteria for this latter group include N-polyoxyethylene fatty acid triethylene glycol low melting point, good liquidity range, water solubil 30 amides 3,5,5-trimethyl-2,4- ity, other solubility, solvent activity, inertness or func 6-propylpiperonyl butyl oxadolidinedione diethylene glycol ether undecylenic acid tionality, etc. 3-pyridine ethanol veratrole TABLE IV w Biologically Compatible Buffer Agents and Zwitterionic Buffers cyclohexyl aminoethane sulfonic N, N-bis (2-hydroxyethyl acid glycine) cyclohexyl aminopropane sulfonic N'-2-hydroxyethyl piperzine acid N'-2-ethane sulfonic acid N'-2-hydroxyethyl piperazine piperazine-N,N'-bis (2-ethane N'-2-propane sulfonic acid sulfonic acid) imidazole N-tris (hydroxy methyl) methyl glycine 2-N-(morpholino)ethane sulfonic N-tris(hydroxy methyl) methyl-2- acid amineothane sulfonic acid morpholino propane sulfonic acid tris (hydroxy methyl)methyl aminopropane sulfonic acid

TABLE V Other Representative Materials Suited for pyrrolidinone, 2 viologens Use in EMP Media in Biological Systems polyethylene glycol-p-iso vital stains octyl phenyl ether valerolactone e-acetamidocaprioc acid farnesol steroids, natural and derived, vitamins K, A, & derivatives L-a-acetamidorf-mercaptopro- fructose e.g., ex-lanolin wetting agents pionic acid D-gluconic acid 8-lactone 50 salicylamide acetamido phenol glutathione sorbic acid acetanilide glycerophosphoric acid tannins allantoin 2,6,10,15,19,23-hexamethyl cis-terpinhydrate alantolactone tetracosane tetrahydro-3-furanol i-allyl-2,5-dimetholy-3,4- 3-hydroxy-2-butanone tetrahydrofurfuryl alcohol methylene dioxybenzene 2-hydroxybenzyl phosphinic polyethylene glycol n-amyl butyrate acid 55 3,7,11,15-tetramethyl-2- anhydromethylene citric acid N-(2-hydroxyethyl)palmitamide hexadien-1-ol B-L-arabinose 5-hydroxy-2-hexenoic acid 2,6,10,14-tetramethylpen arabitol lactone tadecane arachidonic acid 2,6,10,15,19,23-hexamethyl tetraethylene glycol dimethyl benzylacetate 2,6,10,4,18,22 ether 1,3-bis(hydroxy methyl) urea tetracosahexene bis(2-ethylhexyl) 2-ethyl 15-hydroxy pentadecanoic acid thiamine, sales & derivatives hexylphosphonate E-lactone ethoxy (10-20) glucose 5-hydroxy-2 (hydroxy methyl)- ethyl linoleate 4-pyrone EMP media components may be applied to an organ ethyl levulinate 3-hydroxytrimethyldodecanoic ism through known techniques, including injection and 3-ethyl-1-hexanol acid, 3,7,11 2-ethyl-2-methyl succinimide ichthymall local profusion. 2-ethyl sulfonyl ethanol isoascorbic acid 65 EMP in living organisms or in tissues may be oper ethylene glycol diacetate iso-eugenol 1-ethynyl cyclohexanol inositol hexaphosphoric acid ated at threshold currents on the order of 0.002 eugenol isopropyl myristate pa/cm or higher, at voltages of 0.3 v/cm or higher. If iso-valeric acid slower EMP response is acceptable for a particular use, 4,146,454 37 38 thresholds of 0.0005 A/cm may be utilized with volt Selection of a suitable suppressant solvent should take ages as low as 0.05 V/cm. into account the effect of the suppressant on protein Related to the use of EMP in biological systems is the migration. Thus compounds (10), (11) and (13) above use of EMP to mobiolize biochemical species including may beneficiate protein mobility, whereas (3), (4), (9), high threshold ones as proteins - globulins, enzymes, (14) and (18) may be less potent in this regard. polypeptides, nucleic acids, steroids, lipids, lipoproteins Additional solvents for biochemical compounds in and fatty acids. Proteins and other biochemical com clude alcohols such as methyl carbitol, phophonates pounds are susceptible to thermal and chemical degra such as diethyl ethyl phosphonate, lactones such as dation, and are commonly handled in aqueous solution, 6-hexanolactone and sugars. often in chilled, buffered electrolyte solution. However, 10 Solvent compatibility with the substrate is another water as a major component in EMP media has the consideration. With improper solvent selection, the disadvantages of forming electrolytic solutions and of solvent may attack the substrate resulting in altered being rather evaporative. Thus special attention has porosity, structure collapse or similar effects. Proper been given to the adaptation of high water content solvent selection in media formulation permits use, for 15 example, of ion-exchange of "thinlayer' plates, as well systems to EMP usage, and also to the application of as cellulose derivative films such as the nitrate or ace EMP to proteins and related substances in nonaqueous tate, or agarose, acrylamide or silica gels impregnated systems. Since the activity of biochemical compounds is with EMP media. linked to their structural integrity and sensitivity, an The excessive use of potent suppressants may result in additional aim has been formulation of a versatile set of 0 a system with internal resistance so high that substantial media which preserve this activity. resistive heating results, especially where high thresh The general technique for formulation of an aqueous old current operation is indicated. Thus, selection of the EMP media for protein transport involves reducing the less potent suppressants is often satisfactory. The Tc conductivity of water by addition of a suppressant, requirements of proteins and related substances are adjusting the dielectric constant by addition of a high 25 often in the range of 4.6 ma/50 cm or more on a cellu dielectric constant material if necessary, and adding lose substrate as opposed to 1.2 ma/50 cm or less for initiators and/or mobilizers to beneficiate the move most other compounds. ment of the proteins. Reducing the water content of EMP media as de As disclosed above, it has been found that a number scribed above may alter the dielectric constant of the of compounds will suppress the conductivity of water 30 media. This change may be offset, with resulting re to varying extents, thereby alleviating the problem of establishment of the high dielectric constant desirable high conductivity in aqueous media. These compounds for EMP, by addition generally of very high dielectric also function as miscible protein solvents. The conduc constant components. Examples of suitable materials for tivity suppression results are set out in the form of an this dielectric constant adjustment include hydroxy example below. 35 ethyl formamide, N-methyl formamide, formamide, EXAMPLE 24 N-methyl acetamide and related compounds. Gener ally, N-alkyl and N-aryl amides are useful. Often these Various protein-compatible solvents were combined compounds, especially, when of only commercial pu with water (volume ratio = 16/9). Pure solvents were rity, will tend to increase the conductivity of the media, used when possible, as the trace contaminants in com thereby opposing the suppressant mechanism. Such mercially available materials can affect conductivity conductivity contribution may be used to compensate suppression. (This is illustrated by the values given for for an overly high internal resistance caused by a strong compounds (7) and (18) below which are the same sub suppressant. stance obtained from two different sources.) Relative High threshold values of biochemical species may be values of conductivity suppression as compared to the 45 advantageously reduced, and the mobility of the species conductivity of water were: in EMP increased, by the use of initiators and mobiliz ers. Many proteins were found to be particularly sus (1) thiodiethylene glycol 2.2 ceptible to the influence of proton acceptor substances (2) 2,6-dimethyl morpholine 2.6 in increasing mobility, but were relatively indifferent to (3) methoxyethoxy ethanol 2.6 (4) 2-pyrollidone 2.7 50 mobilization by proton donor molecules. Initiator sub More strongly conductivity suppressing compounds are: stances, though in relatively low concentration, con (5) 6-butyrolactone 3.3 (6) sorbitol 3.8 tribute susbstantially to the lowering of threshold cur (7) 1,3-butanediol 3.6 rent, and if they also act as mobilizers, to the enhance (8) propylene glycol 3.6 ment of species mobility. For proteins, initiators may be (9) dimethyl formamide 3.6 A group of increased strength suppressants are: 55 used to bring threshold levels down from 4.6 ma/50 (10) dimethyl acetamide 4.8 cm to 3.4 to 1.0 ma/50 cm (20LA/cm) with voltages (11) tetrahydrofurfuryl alcohol 4.6 (12) butoxyethoxy propanol 5.0 in the 50 to 25,000 v/cm range. Typical initiator sub (13) 6-hexanolactone 5.0 stances, mobilizers, and worthwhile solvents are: ni (14) oxydiethanol S.4 trobutanol; 3-acetyl 3-chloropropylacetate; salicylalde (15) diacetin 5.6 60 hyde; N-methyl-acetamide; boric acid; phenols; guaia The truly potent class of suppressants for water may be col; fumaric and barbituric acids; piperazine; furfural; represented by: tributoxyethylphosphate; 3,3,3-trichloro-t-butyl alco hol; dimethyl-1,3-dioxolane-4-methanol; 2-ethyl sulfo (16) 2-[2-(ethoxyethoxy) ethoxyl ethanol 8.3 nyl ethanol; tetrahydrofurfuryl alcohol; N-substituted (17) 1-2-(2-methoxy-1-methyl ethoxy) 65 pyrollidones; dimethyl sulfoxide; 2,2-oxydiethanol; eth -1-methyl ethoxy-2-propanol 10 ylene cyclic carbonate; tetramethyl urewa; thiodiethyl (18) 1, 3 butylene glycol 12 ene glycol; 1-ethynyl cyclohexanol; tetrahydro-3 fura nol, 2,6-dimethyl-m-dioxan-4-ol acetate; and 2,5-bis 4,146,454 39 40 (hydroxy methyl) tetrahydrofuran, other amides, par insoluble in water. The collagenous substances, as well ticularly N-alkyl and dialkyl and hydroxy amides, other as elastins and reticulins are particularly resistant to proton acceptors and buffer systems. Very often high solubilization in aqueous media, whereas they are solu dielectric constant substances will act as mobilizers or ble in nonaqueous media. initiators. 5 The media for EMP transport of proteins may in Electrophoresis of proteins is often done in high pH clude other protein solvents chosen to provide particu (alkaline) buffer because of the dependence in electro lar properties, such as glycols, amides, ethers, pyrrol phoresis on isoelectric points. In contrast, EMP trans idones, lactones, sulfoxides, phenols, alcohols and phos port of proteins may be carried out in acid media. Buff. phonates. ers may be prepared from the list of biologically com 10 Suitable aqueous systems for the transport of prote patible agents given above, or may be of the more com ins, in accordance with the foregoing table of suppres monly used Tris, Veronal or Sorensen types. In addi sants using a solvent/water volume ratio of 16/9 are: tion, more common organic acids and bases may be 16 ml. thiodiethylene glycol used. Examples of acid buffers useful for EMP transport 9 ml. water of proteins and related substances are: 15 2 drops ethanolamine tetra methyl ammonium hydroxide/acetic acid (separation of protein mixtures including triethylene tetramine/2,2-oxydiacetic acid cytochrome C and myoglobin - electrical dimethyl amine/picric acid characteristic of 1.8 Kv1.2 ma) diethanolamine/dichloracetic acid 16 ml. 6-hexanolactone triethanolamine/dichloracetic acid 20 9 ml. water piperazine/dichloracetic acid 3 drops ethanolamine Media prepared as described above, with combina (gave protein movement and resolution - tion of water, one or more suppressants, one or more electrical characteristic of 1 Kv/1.2 ma) agents for increasing the dielectric constant, and one or 16 ml. dimethyl acetamide more initiators (and/or mobilizers) may effect separa 25 9 ml H2O tion of proteins within a minute or so in a few centime 4 drops ethanolamine ters of Whatram No. 1 filter paper, while the same (separation of proteins - separation on the same substrate would take up to 16 electrical characteristic of 1.6 Kv/1.2 ma) hours over as much as 15 cm. of substrate with electro The following three examples illustrate nonaqueous phoresis. 30 media representative of those which have been used for A number of proteins and related substances are in EMP transport of human and bovine albumin, hemoglo soluble in water. For example, some derived or conju bin, cytochrome C (an enzyme), myoglobin (muscle gated proteins, as well as some polypeptides, keratins protein) and pancreatin. In addition, proteins have been and prolamines, are water insoluble. While this problem separated from whole blood in experiments in which may be overcome in some instances, as with Zein (prola 35 the cell debris remained at the origin. Phenol was a mine) by use of the modified aqueous media described useful media component in these last separations. above, the use of nonaqueous media provides additional flexibility. EXAMPLE 25 An alternative to aqueous EMP systems for proteins 12 ml. -ethylene cyclic carbonate and other biochemical compounds is the use of other 6 ml. - ethoxyethoxy ethanol solvents analogous to water in proton donor number 6 ml. - thiodiethylene glycol (DN= 18.0 for water) and dielectric constant 6 drops tris-dichloracetic acid buffer (DC-81.0 for water). Especially useful are ethylene cyclic carbonate (DN=16.4, DC=89.1, boiling point EXAMPLE 26 (BP) = 245° C) and propanediol-1, 2-carbonate 45 7 ml. -ethylene cyclic carbonate (DN= 15.1, DC= 69.0, BP=240° C). These solvents 7 ml. - ethoxyethoxy ethanol contribute superior heat stability to the media formula 9 ml. - oxydiacetic acid tion, permitting operation with greater resistivity and 1.5 ml. - formamide higher voltage gradients without need for external cool 6 drops tris-dichloracetic acid buffer ling. 50 Certain solvents show a more intense solvent action EXAMPLE 27 than does water for some proteins. Thus, keratins which 10 ml. -ethylene cyclic carbonate are water insoluble may be dissolved in other solvents 4 ml. - N-methyl pyrrolidone such as dimethyl sulfoxide. Prolamines may be solubi 3 ml. - furfuryl alcohol lized in glycols, glycol ethers and certain alcohols. 55 2.5gm. - boric acid Solvents of moderate to strong proton acceptor prop 4 ml. - 1,3-butylene glycol erties are suitable for protein solubilization, and may 16 drops piperazine-dichloracetic acid buffer (Ph3.7) even form the basis of the media. Solvents of this type Acridine orange (fluorescent indicator) . include iodine monochloride, sulfer dioxide and hydro The following example illustrates EMP media and gen fluoride. For example, anhydrous hydrogen fluo 60 electrical conditions used for the separation of albumins ride is a good solvent for fibrous proteins normally and especially globulins.

ELECTRICAL CHARACTERISTICS EXAMPLE SOLVENT FORMULAE (Stabilized) 28 10ml. ethylene cyclic carbonate 5.2 KVA2.0-3.6ma 4 ml, butylene glycol, 4 ml. Whatman #1 methyl pyrrolidonone, 2 ml. (10 cm.) 41 4,146,454 42 -continued ELECTRICAL CHARACTERISTICS EXAMPLE SOLVENT FORMULAE (Stabilized) formamide (initiator), 2.5g boric acid, 3 ml. furfural (pH buffer and mobilizer), 16 drops piperazine dichloroacetic acid buffer pH 3.7 (pH buffer and mobilizer), acridine yellow (fluorescent indicator) The same media was used to separate cytochrome C, tion of the techniques of formulation of liquid EMP hemoglobin, myoglobin, albumin, yohimbine, and atro media to gaseous media formulation led to the achieve pine under the following conditions: ment of high levels of conductivity without the need for

ELECTRICAL - CHARACTERISTICS EXAMPLE SOLVENT FORMULAE (Stabilized) 29 10 ml. ethylene cyclic carbonate, 4.4 KV/3.6ma; 4 ml. butylene glycol, 4 ml. 2.2 KV/1.2ma methyl pyrrolidinone, 2 ml. Whatman #3 formamide (initiator), 2.5g boric acid, 3 ml. furfural (pH buffer and mobilizer), 16 drops piperazine dichloroacetic acid buffer pH 3.7 (pH buffer and mobilizer), acridine yellow (fluor escent indicator) The use of dyes which act as tracers may be desirable in some cases to visually follow the separation of color high potential. The aim in construction of a gaseous less biochemical species. See examples 27-29 above. It EMP media is to increase the conductivity level of the must be established that the particular dye does not 30 gas to the level of semiconductivity or other level con interfere with the resolution process itself. Bromphenol venient for the desired application. blue has been commonly used with serum proteins, but Industry has made use of gases largely as insulators. may migrate separately from the protein in EMP. For Most gaseous conduction performed currently focuses redox sensitive materials, methylene blue is often suit on the high dielectric characteristics of gases generally. able, and glutathione either in oxidized or reduced form 35 The conduction commonly takes place within an enve may be used to buffer against redox reactions. Saframin lope or other controlled environment in a relative vac type dyes bind to and alter the solubility characteristics uum with the use of an energy source (such as a thermo of proteolytic enzymes and can therefore be useful in electric filament) to control conduction. In such devices separating them from other materials. A few milligrams the presence of materials of lesser dielectric character is of an easily coupled fluorescent tracer such as acridine deleterious. Gaseous conductivity is also of importance orange will allow visual observation of many substances currently in the area of ionization or the plasma state. including proteins under ultraviolet light without alter Attempts have been made to produce electricity ing their migration characteristics. Other tracers such as through the motion of conductive gases relative to a brightening agents, fluorescent coupling agents, and magnetic field (magnetogasdynamics) but it has been even fluorescent antibody material may be useful in 45 found necessary to employ temperatures so high that following protein transport. Additional tracer agents corrosion of the containers resulted. It is now possible for biochemical and other work are vital dyes such as to achieve conductive gases at or near room tempera the flavines and primulin. Nile blue may be especially ture through the use of EMP, and thereby may be possi useful alone or in combination with other dyes under ble to provide a practical means for producing electric U.V. and daylight. Neutral red with aesculin remains 50 ity. sensitive at about 1000x dilution with daylight alone. Formulation of gaseous EMP media provides a useful The U.V. dyes are also convenient for localizing weak scientific technique for investigating the molecular positive or negative charges in biological structures. characteristics of materials. In addition, it may be em Antibodies or other coupling tracer materials as well as ployed in the construction of controlled gaseous con radioactive derivatives can also be useful, e.g., rhoda 55 duction devices used for wireless transmission (e.g., in mine B-isothiocyanate; fluorescein isothiocyanate; p coilless transformer cores), in light emission studies, isothiocyanato acridine; 4-chloro methyl-1-acridine; gaseous charge transport, gaseous molecular transport, 1-ethyl-2-(-3-(1-ethyl naphthol (1,28) - thiazolin-2- electrically mediated gaseous diffusion, and low poten ylidine)-2-methyl propenyl-naphth (1,2) thiazolium tial spark gap devices. EMP media formulation may be bromide. Additional possible tracers are phenazine me employed to modify fuel combustion systems and the thosulfate, Remazol brilliant blue R, thiazolyte tolue, fuel itself in combustion engines so as to extend the protoporhyrin. IX, citrazinic acid, quinine, lisamine, spark propagation distance (e.g., allow separation of the rhodamines, cleves acid and umbelliferone. spark plug electrodes by larger distances thus relying Another aspect of the present invention is the use of less on explosive propagation). the technique of EMP media formulation to fabricate Similar principles to those applied in preparation of gaseous semiconductive media which will allow con liquid semiconductive EMP media are applied in the trolled conduction without need for evacuation, very preparation of gaseous semiconductive EMP media. high temperatures, or very high voltages. The applica Media containing a number of components, such as 4,146,454 43 44 three- and four-way systems, are necessary to effect a A further aspect of the present invention is the prac substantial alteration in conductivity of the gas to bring tice of EMP within a gel. The gel consistency may it into the semiconductive range. Agents which acting range from fluid to rigid. Gels generally are susceptible together facilitate proton donor/acceptor interaction, to resistance adjustment by addition of a small amount increased conductivity and enhanced dielectric con of conductivity agent with a material of high dielectric stant are indicated. constant such as formamide or another amide or alkyla For example, water acts by hydrogen bonding in the mide derivative and a coupling solvent if necessary to vapor phase as both a donor and acceptor molecule, improve miscibility. The EMP media may be washed interacting with proton donors ranging from strong into the gel or the gel fabricated with the media in it. acids to alkanols (e.g., 1,1,1,3,3,3,-hexafluoropropan-2- 10 One difficulty with the use of gels as EMP media is that ol) and with acceptors such as amines (including pyri by products left over from the gel formation process dines), ethers, alcohols and ketones. In general, the must be removed if they interfere with the EMP con more conductive or active EMP solvents have been ductivity adjustment and transport. found particularly suited to gaseous conduction. (See Agar gel, polyvinyl alcohol (PVA), silica gel, starch the list of active agents above.) Also, comixing of mate 15 gel, Carbopol (carboxypolymethylene) and "Crash Safe rials helps to effect enhanced conductivity. Aviation Jet Fuel" (additive-modified kerosene) are For example, placing a few drops of triethylene tetra examples of gels which function as EMP media when mine in the base of a glass test tube seated in a mildly doped with the appropriate conductivity-modifying heated sand bath reduced the resistance between the agents in accordance with the principles described electrodes located 0.5 cm apart and 2.5 cm. from the 20 above. Acrylamides could also be employed. An exam bottom of the tube to 10 ohms from more than 10 ple of a gel fabricated with an EMP solvent within it is ohms in air. The addition of a small crystal of iodine PVA gelled with tetrahydrofurfural alcohol. Tetraethyl reduced the resistance to less than 8 x 10 ohms. Addi ortho silicate which gives a clear glass-like gel with tion of formamide instead of iodine gave 1.5 x 10 numerous organic gels permits compatability with vari ohms, and two together reduced to less than 5 X 10 25 ous organic EMP media. Gelatin also provides a clear ohms. With some media, resistances in the hundreds of gel base. Examples of chemical species which may be ohms were obtained at low voltages (5-10v) near room transported in such gels include dye molecules, and temperature and atmospheric pressure. even particulate matter may be moved at fast rates in a As a further example, in such a cell, at a five volt "fluid' gel such as crash safe aviation fuel. potential, a media was formulated from agents (A.) 30 Voltage and current levels are adjusted just as in added stepwise by measuring the resistance (B.) ob cellulose supported EMP. A slightly higher current, tained after each step in the sequence of addition (C.) than 1.2 ma/50 cm can also be used for thin slabs of gel (to "). Otherwise, gels "to "thick or greater require careful current consideration to avoid excessive heat (C.) Sequence 35 of Addition buildup. Cumulative In EMP separation processes, gels are capable of (B.) Resistance Amount Amount in providing enhanced resolution because of their fine (A) Agent in Cell Added Mixture pore structure. EMP induced movement of dye mole Tetra methyl o (> 100 megohms) 5 pts 5 pts e cules within a gel may be used as an analytical tech + N-methyl 1.70 megs) 1.5 pts 6.5 pts nique to study the structure and properties of the gel acetamide itself, + l2 75 kg) 1 pts 7.5 pts -- diethylamine 18 K () 1.5 pts 9 pts The apparatus used for gel EMP differed from that used for liquid EMP in that the filter paper substrate was replaced with the gel. Agents which are useful to formulate gaseous EMP 45 Media include iodine, other halogens, amines, volatile EMP within a gel is illustrated by the examples be salts, amides, nitro derivatives including nitrosylchlo low. ride, acid chlorides, hydrazine, oxyhalides, sulfer diox ide, hydrogen fluoride, ammonia, or other potent pro EX. SOLVENT FORMULAE 50 30 glycol, ammonium bromide (to form a saturated ton donor or acceptor molecules, combinations thereof, solution in N-methyl pyrolidinone), and and substances liberating such. Semiconductive media formamide, formulated from such components according to the 31 5% weight/volume ceresin or microwax in 20% principles of liquid media formulation as modified or 30% xylene plus EMP media components appro above provide a controllable conductive gaseous envi priate for use with xylene. ronment even at atmospheric pressure in air. The use of 55 high boiling chemicals as classified for liquid EMP The EMP media components referred to in Example media use requires an elevated temperature to produce 31 may be the four-way system described at page 12 or the gaseous EMP effect. Use of lower boiling solvents is ammonium bromide in methoxy ethoxy ethanol, 202 therefore advantageous in the preparation of gaseous ethoxyethoxy) ethanol, dimethyl formamide, dimethyl EMP media. acetamide, dimethyl sulfoxide, n-butanol, or N-methyl Gaseous EMP media may be subjected to voltages of, pyrrobidinone. for example, 0.5 to 30,000 v/cm, with continuous con EMP is susceptible of application to a wide variety of duction (rather than sparking) resulting. Modifying uses, a number of which have been detailed above. The agents may be included in the media so as to make it application of EMP to several specialized areas will be susceptible to arc over in the range of 50 to 30,000 v/cm 65 further described here. and therefore useful in fuel systems so as to modify or EMP may be used in conjunction with media phase extend the spark propagation properties and/or electro control to provide an information storage, processing thermal vaporization prior to ignition. and display mechanism. For example, a media may be 4,146,454 45 46 used which is solid at ambient temperature, which melts may be used for adjusting the glass to EMP media re or at least increases in fluidity when warmed. Dye mol quirements. ecules or other detectable or traceable materials in the EMP may be conducted in other solid media by ap media may be transported by application of a potential plying heat energy to liquify the media during EMP and difference when the media is fluid, and stored with allowing the media subsequently to solidify. For exam display capabilities when the media is rendered non ple, N-methylacetamide was heated above its melting fluid. The system is non-volatile; the resolidification point and placed on a paper strip (Whatman No.1). The curtails diffusionary information loss, and the position paper strip was suspended between electrodes, rhoda ing of the dye spots in the solidified media provides for mine and ink dyes were then placed on the filter paper information storage. Gel or porous media might also be 10 and a potential applied across the paper. After the rho used for information storage and display. A permeable damine dyes migrated, the molten n-methyl-acetamide solid support substrate may be incorporated in the sys was allowed to cool and solidify. tem to minimize thermal diffusion. By use of a transpar Photoconductive materials, such as polyvinyl carba ent substrate with refractive index approximating that zole, may be employed in conjunction with EMP effec of the liquid media, additional clarity can be achieved. 15 Parallel capillaries, e.g. of glass, may be used to limit tuated information storage, processing and display. For diffusion and fix the geometry of the system. Transpar example, in an information reproduction system, a con ent electrodes (e.g., NESA glass) may be used for dis ductive substrate may be coated with polyvinyl carba play purposes. Zole. Where light passing over or through the docu EMP is particularly suited for this application in a 20 ment, film, object or other image to be reproduced number of respects. The high response speed of EMP strikes the polyvinyl carbazole, a short circuit will oc systems would allow, for example, response times of cur, and dye molecules contained in a juxtaposed EMP less than a second with a 10 cm/min transport rate media will not be caused to move or will be under a between parallel plate electrodes 1 mm apart. In addi reduced potential and therefore subject to reduced tion, different threshold currents may be used to selec 25 movement. Where light does not strike the polyvinyl tively transport a sequence of chemical species for su carbazole, dye molecules may be mobilized or depos perimposed displays within a single EMP unit or cell. ited. Because of the fast molecular migration achieved The components of EMP media which are suitable with EMP, such a reproduction process could be car for use in an information storage and display system are ried out at a much lower voltage than used in conven generally those with melting points in the neighborhood 30 tional electrostatic techniques. For example, a process of room temperature. From any class of compounds of the type disclosed in U.S. Pat. No. 3,384,566 to Clark whose use in the media is indicated, one or more media could be modified with use of EMP for operation at components may be chosen for their melting point. For lower voltage and enhanced transport rates. example, the class of phenols offers the following EMP may be employed to obtain a number of electro choices: optic effects. For instance, it may be used in a manner 35 analogous to electrophoresis in fluid glas-sandwich display techniques. See Fluid Glass-Sandwich Display Compound Melting Point Technique Permits Large, Multicolored Characters, 22 2,4-dichlorophenol 40-42 2,4-dimethylphenol 22-24 Electronic Engineering Times (March 29, 1974). EMP 2,6-dimethylphenol 45-47 would provide the advantages of faster response, wider 2,4-ditertiary-pentylphenol 24-26 2,6-ditertiary-butyl phenol 35-36 selection of materials and less heat generation compared 2,6-ditertiary-butyl-p-cresol 62-68 to electrophoresis in such an application. EMP could o-ethoxyphenol 25-27 p-methoxyphenol 54-56 also be used in place of electrophoresis in applications 1-phenyl-2-propanol 36 such as that described in U.S. Pat. No. 3,511,651 to thiophenol 70-75 45 Rosenberg. EMP Media may additionally be used in electrochromic devices to form the junction material Lower melting compounds, such as 3-phenyl-l- between the electrochromic material of, e.g., molybde propanol (MP= -18° C) and m-thiocresol (MP= -20 num trioxide on NESA glass and the second electrode. C.) may be useful in combination with one or more of (Sulfuric acid has been employed as the junction fluid in the compounds listed above. 50 the past.) The technique of EMP media formulation The use of EMP with melts is not restricted to room may be used to modify or study liquid crystals. temperature melts. Additional media components The technique of EMP media formulation may also which may be employed include resins, glasses, glazes be used to modify the Kerr effect (alteration of a materi and chalcogenides. Glycol-boric acid glasses are low al's influence on polarized light by imposition of a high melting glasses suitable for EMP media. Various mole 55 voltage electric field) in various liquids. ratios of boric acid or boric anhydride fused with most Electromagnetic fields in addition to the driving volt glycols yields a rigid transparent glass at room tempera age may be employed in connection with EMP for ture, suitable for modification for EMP use. Starches, various purposes. A second electrode set at angles to sugars, amines, borax and many other compounds can the set providing the driving voltage may be used to also enter into the glass formation. Increasing the ratio cause the chemical species being transported to swerve of glycol or amine to the boric acid adjustably lowers from a straight line path. Similarly, one or more elec the melting point. Similarly, agents such as metallic trodes angulated to the set providing the driving volt sterates can act as crystallization retardants and can be age may be used to compensate for any slight lateral used with, for example, sugars to produce glassy EMP deviation or spreading of a species traveling on a sub media. Rosin and methacrylates are other organic glass. 65 strate and to counteract the effects of diffusion. In addi forming media. Inorganic glasses can be derived from tion, a balanced electrode pair may be placed perpen phosphates, tellurium, selenium and other materials. dicular to the path of the chemical species transported, Iodine, as well as other compatible conductivity agents and used to detect the passage of various zones of chem 4,146,454 47 48 ical species based on the change in electrical forces micro amps/cm or at least 20 microamps and equal to between the second set of electrodes. or exceeding the threshold current value for the bio Pulsed DC fields may be used instead of a constant chemical species in the medium, below which value the DC driving force to reduce media heating. As an addi biochemical species remains substantially stationary. tional modification, an AC field may be superimposed 5 Where EMP is carried out on a support member, an on the DC driving force to mediate the dielectric and adsorbant may be used, such as cellulose, cellulose ace semiconductive properties of the media, as well as to tate, cellulose nitrate, alumina, silica, glass, asbestos, take advantage of the Debye-Falkenhagen (solvent) wood, flour or resin as Teflon, Pevikon, or ion ex effect. change resin as Amberlite or modified cellulose, or Magnetic fields may be employed to modify the EMP 10 molecular sieve resin as Sephadex, or mineral as process. A magnetic field, preferably on the order of diatamaceous earth or apatite. kilogauss or greater, applied at right angles to the EMP I claim: voltage will by virtue of the Faraday magneto-optic 1. A process which comprises imparting mobility to a effect, cause the D and L forms of stereoisomers trans chemical species by providing a semiconductive trans ported under the influence of EMP to separate into 15 distinct paths. This procedure must be carried out in an port medium and impressing a voltage of about 0.05 to apparatus of special design. A suitable EMP cell com 25,000 volts/cm across the medium sufficiently high to prises two separable electrode compartments and sub produce a current density in the range of about 0.001 to strate (e.g., filter paper) clamping means. These com 400 microamp/cm and equal to or exceeding the partments are mechanically fixed in position so as to 20 threshold current value for the species in the medium, allow the pole faces of a powerful electromagnet to be below which value the species remains substantially brought within close proximity to the top and underside stationary, to induce a high mobility rate for the species. of the substrate surface. An insulating film such as 2. The process of claim 1 wherein the current density mylar can be used to retard arc-over to the pole face. is in the range of about 0.002 to 100 microamp/cm2. Magnetic fields may be used to stabilize the media so 25 3. A process which comprises imparting mobility to a as to reduce long-term diffusion of a molecular species chemical species by providing a fluid semiconductive during a continuous EMP process in a manner analo transport medium containing a component selected gous to that described for electrophoresis in Kolin, from the group consisting of mobilizers and initiators Continuous Electrophoretic Fractionation Stabilized by and impressing a voltage within the range of about 0.05 Electromagnetic Rotation, 46 Chemistry 509 (1960). 30 to 50 volts/cm across the medium sufficiently high to Unlike the Kolin application, there is no significant produce a current density in the range of about 0.001 to stabilization problem in EMP due to thermal factors. 4 microamp/cm and equal to or exceeding the thresh Further, whereas it has been found that the magnetic old current value for the species in the medium, below response of the migrating species in the aqueous electro which value the species remains substantially station phoretic media was nil, the response of species in EMP 35 ary, to induce a high mobility rate for the species, media as well as the media itself, will differ from elec 4. The process of claim3 wherein the current density trophoretic aqueous media, and can be further modified is in the range of about 0.002 to 0.2 microamps/cm2. and controlled. 5. The process of claim 3 wherein the chemical spe The invention herein includes the processes of im cies is on a filter paper support member in the medium. parting mobility to or separating chemical species by 40 6. The process of claim 3 wherein the initiators are providing a semiconductive transport medium (which selected from the group consisting of acetamide, form may be liquid, gaseous or solid) and impressing a volt amide, propionamide, butyramide, hexanamide, lactam age of about 0.05 to 25,000 volts/cm across the medium ide, stearamide, nicatinamide, nepecotamide, benza sufficiently high to produce a current density in the mide, n-toluamide, salicylamide, iso-valeramide, the range of about 0.001 to 400 microamp/cm or .002 to 45 methyl, ethyl, propyl, hydroxyethyl, butyl, cyclohexyl 100 microamps/cm and equal to or exceeding the or methylal N-substituted and the methyl, ethyl or pro threshold current value for the species in the medium, pyl N, N-disubstituted derivatives of the foregoing below which value the species remains substantially compounds, and wherein the mobilizers are selected stationary, to induce a high mobility rate for the species. from the group consisting of guiacol, salicylaldehyde, In an aspect of this invention the fluid semiconductive 50 boric acid, tetrahydrofurfuryl alcohol, tributoxyethyl transport medium contains a component selected from phosphate, and 3-acetyl-3-chloropropyl acetate. the group consisting of mobilizers and initiators and 7. The process of claim 3 wherein the transport me comprises impressing a voltage within the range of dium exhibits non-linear electrical characteristics upon about 0.05 to 50 volts/cm across the medium suffi application of the voltage. ciently high to produce a current density in the range of 55 8. The process of claim 3 wherein the chemical spe about.001 to 4 microamp/cm, or from about .002 to 0.2 cies is non-polar. microamps/cm and equal to or exceed the threshold 9. The process of claim 3 wherein a second voltage is current value for the species in the medium, below impressed across the medium at an angle to the first. which value the species remains substantially station 10. A process for separating chemical species which ary, to induce a high mobility rate for the species. 60 comprises mixing said species with a fluid semiconduc Where the fluid semiconductive medium comprises tive medium containing a component selected from the water, a conductivity suppressant, a high dielectric group consisting of mobilizers and initiators and apply constant component, and a component selected from ing a voltage within the range of about 0.05 to 50 the group consisting of mobilizers and initiators, the volts/cm across the medium to produce a current den process for imparting mobility to a biochemical species 65 sity in the range of about 0.001 to 0.2 micro amp/cm2 is carried out by applying a voltage within the range of and equal to or exceeding the threshold current value about 0.05 to 25,000 volts/cm across the medium suffi for at least one species in the medium below which ciently high to produce a current density of at least 2 value the species remains substantially stationary. 49 4,146,454 11. A process which comprises imparting mobility to 50 a biochemical species by and applying a voltage within the range of about 0.05 to providing a fluid semiconductive medium comprising 25,000 volts/cm across the medium sufficiently high to water, a conductivity suppressant, a high dielectric produce a current density of at least 2 microamps/cm constant component, and a component selected and equal to or exceeding the threshold current value from the group consisting of mobilizers and initia for the biochemical species in the medium, below which tors, and tionary.value the biochemical species remains substantially sta applying a voltage within the range of about 0.05 to 25,000 volts/cm across the medium sufficiently 23. The process of claim 22 wherein the nonaqueous high to produce a current density of at least 2 solvent is selected from the group consisting of ethylene micro amps/cm and equal to or exceeding the 10 cyclic carbonate, propanediol-1,2-carbonate, dimethyl threshold current value for the biochemical species sulfoxide, glycols, glycol ethers, alcohols, iodine mono in the medium, below which value the biochemical chloride, sulfur dioxide, and hydrogen fluoride. species remains substantially stationary. 24. The process of claim 22 wherein the non-aqueous 12. The process of claim 11 wherein the conductivity 15 solvent is selected from the group consisting of ethylene suppressant is selected from the group comprising thio cyclic carbonate and propanediol-1,2-carbonate. diethylene glycol; 2,6-dimethyl morpholine; methoxy 25. The process of claim 24 wherein the semiconduc ethoxyethanol; 2-pyrollidone; y-butyrolacetone; sorbi tive medium further comprises a phenol. tol; 1,3-butanediol; propylene glycol, dimethyl form 26. The process of claim 22 wherein said voltage is amide; dimethyl acetamide; tetrahydrofurfuryl alcohol; 20 about 0.005 to 25,000 volts/cm and the current density butoxyethoxy propanol; 6-hexanolacetone; oxydietha is at least 20 microamps/cm. nol; diacetin; ethoxy ethoxy ethoxy ethanol and me 27. The process of claim 22 wherein the biochemical thoxymethoxy methoxyethoxy methoxy propanol. species is selected from the group consisting of human 13. The process of claim 11 wherein said voltage is in albumin, bovine albumin, hemoglobin, cytrochrome C, the range of about 50 to 25,000 volts/cm and said cur 25 myoglobin, and pancreatin. rent density at least about 20 microamps/cm. 28. The process of claim 22 wherein the semiconduc 14. The process of claim 11 wherein the biochemical tive medium further comprises a tracer for the biochem species is on a support member in the medium selected ical species. from the group consisting of ion-exchange plates, thin 29. The process of claim 28 wherein the trace is se layer plates, cellulose derivative films, agarose gels, lected from the group consisting of methylene blue and acrylamide gels, and silica gels, 30 acridine orange. 15. The process of claim 11 wherein the high dielec 30. A process for effecting condition in a gas which tric constant component is selected from the group comprises providing a multi-component gaseous semi consisting of amides, N-alkyl and N-aryl amides. conductive medium containing components with pro 16. The process of claim 11 wherein the high dielec 35 ton donor/acceptor interaction capability, high dielec tric constant component is selected from the group tric constant and high conductivity and applying a volt consisting of hydroxyethyl formamide, N-methylform age of about 0.05 to 30,000v/cm to achieve continuous amide, formamide, and N-methyl acetamide, conduction. 17. The process of claim 11 wherein the component 31. The process of claim 30 wherein the semiconduc selected from the group consisting of mobilizers and 40 tive medium comprises components selected from the initiators is a proton acceptor. group consisting of strong acids, alkylols, amines, 18. The process of claim 11 wherein the component ethers, alcohols, ketones, halogens, volatile salts, am selected from the group consisting of mobilizers and ides, nitro derivatives, hydrazides, acid chlorides, alco initiators is selected from the group consisting of N hol amines, and oxyhalides. alkyl, dialkyl, and hydroxy amides, 45 32. The process of claim 30 wherein the semiconduc 19. The process of claim 11 comprising a component tive medium comprises components selected from the selected from the group consisting of solvents, mobiliz group consisting of triethylene tetramine, formamide, ers and initiators selected from the group consisting of iodine, nitrosylchloride, hydrazine, sulfur dioxide, hy nitrobutanol; 3-acetyl 3-chloropropylacetate; salicy drogen, fluoride, diethylamine, tetramethylurea, N laldehyde; N-methylacetamide; boric acid; phenols; 50 methylacetamide, and ammonia. guaiacol; fumaric and barbituric acids; piperazine; furfu 33. A process which comprises imparting mobility to ral tributoxyethylphosphate; 3, 3, 6, -trichloro-t-butyl a chemical species by providing a semiconductive trans alcohol; dimethyl-1, 3-dioxolane-4-methanol; 2-ethyl port medium within a gel and impressing a voltage of sulfonyl ethanol; tetrahydrofurfuryl alcohol; N-sub 0.05 to 25,000 volts/cm across the medium sufficiently stituted pyrollidones; dimethyl sulfoxide; 2, 2-oxydie 55 high to produce a current density in the range of about thanol; ethylene cyclic carbonate; tetramethyl urea; 0.001 to 400 micro amp/cm and equal to or exceeding thiodiethlene glycol; 1-ethynyl cyclohexanol; tetrahy the threshold current value for the species in the me dro-3-furanol; 2,6-dimethyl-m-dioxan-4-ol acetate; and dium, below which value the species remains substan 2,5-bis (hydroxy methyl) tetrahydrofuran. tially stationary, to induce a high mobility rate for the 20. The process of claim 11 wherein the medium species. further comprises an acid buffer, or alkaline buffer. 21. The process of claim 11 wherein the biochemical 34. The process of claim 33 wherein the semiconduc species is a protein. tive transport medium within the gel comrises a con 22. A process which comprises imparting mobility to ductivity agent and a comonent of high dielectric con a biochemical species in a nonaqueous medium by pro stant. viding a fluid semiconductive medium comprising a 35. The process of claim 37 wherein said current non-aqueous solvent with proton acceptor properties density is from 0.002 to 100 microamps/cm2.