The Journal of Supercritical Fluids

J. of Supercritical Fluids 47 (2009) 598–610

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Multiple unit processing using sub- and supercritical ﬂuids

Jerry W. King ∗, Keerthi Srinivas

Department of Chemical Engineering, 3202 Bell Engineering Center, University of Arkansas, Fayetteville, AR 72701, USA article info abstract

Article history: The past twenty years has seen an expansion of the “critical fluid” technology platform with respect to Received 31 July 2008 using or combining multiple types of unit operations and compressed fluids in both their sub- and super- Received in revised form 14 August 2008 critical states. Although supercritical fluid extraction (SFE) utilizing supercritical carbon dioxide (SC-CO2) Accepted 14 August 2008 has seen considerable industrial use, the high capitalization cost of building and running such production plants promotes expanding their use and functionality with respect to multi-unit operations and Keywords: multiple fluids. An evaluation of the current status of implementing such an approach is provided, and a Carbon dioxide perspective of future needs suggested based on the senior author’s 40 years of experience in critical fluid Critical fluids Multiple fluids processing of agriculturally-derived materials and natural products. The use of hot compressed water Unit processes is no longer limited to just supercritical water processing, but can be advantageously exploited over a Water wide range of temperatures and appropriate pressures to include extraction and reaction of targeted substrates, including bioactive natural products, biomass conversion for renewable fuels, and synthesis of chemicals. As noted previously, combining SFE with fractionation methods using critical fluids, and/or reaction chemistry in critical fluid media can produce a variety of extracts or products [J.W. King, Sub- and supercritical fluid processing of agrimaterials: extraction, fractionation and reaction modes, in: E. Kiran, P.G. Debenedetti, C.J. Peters (Eds.), Supercritical Fluids: Fundamentals and Applications, Kluwer Publishers, Dordrecht, The Netherlands, 2000, pp. 451–488.] however the modification of processing equipment such as expellers, extruders, and particle production devices extend the use of the critical fluid technology platform. Sequential unit processing using multiple fluids also has been reported

although demonstrated to a limited degree—however combining both compressed CO2 andwaterina unit process can also impart some unique processing possibilities. The concept of multiple unit and fluid processing supports an environmentally benign or “green” production platform and is consistent with processing sustainable materials. Integration of critical fluids into existing processing concepts such as biomass conversion, biorefineries, and synthesis based on methyl ester intermediates are discussed. © 2008 Elsevier B.V. All rights reserved.

1. Introduction and other industrial uses, as illustrated in Fig. 1. This approach has been summarized by the senior author and others in previous pub- Supercritical fluids and their liquefied analogues have been lications [1,5,6]. The perspective we offer here is somewhat biased traditionally used in single unit operations, i.e. extraction, fraction- towards past and current studies which focus on advancing multi- ation, using neat SC-CO2 or with appropriate modifiers [2]. Since ple unit and/or fluid processing of agriculturally-derived materials the 1980s, almost 38% of the supercritical fluid extraction pro- or natural products. cesses have been devoted to extraction of food and natural products Despite this focus, the perspective we offer opens other options [3]. Beginning in the mid-1980s, columnar and chromatographic for applying critical fluids in general by embracing the idea of techniques followed by reactions in supercritical fluids were devel- tandem processing using different compressed fluids. Commen- oped to facilitate supercritical fluid derived extracts or products surate with the goal of environmentally benign processing is the [4], thereby extending the application of a critical fluids processing use of liquefied or supercritical CO2 for non-polar to moderately platform beyond SFE. These newer developments were investigated polar solutes, and compressed water between its boiling and criti- in part due to the complexity of many natural product matrices cal points for more polar solutes and reactants. Ethanol, a naturally and the desire to concentrate specific target components for food derivable sustainable solvent, is suggested as a preferred co-solvent to be paired with compressed water or carbon dioxide. This simple, renewable compressed fluids platform has many advantages ∗ Corresponding author. Tel.: +1 479 575 5979; fax: +1 479 575 7926. and can be used to achieve multiple results, particularly when used E-mail address: [email protected] (J.W. King). sequentially, or in tandem with multiple unit processes.

Fig. 3. Coupled processing options for critical ﬂuids.

Fig. 1. Integration of multiple unit critical fluid processing for processing natural products. schemes, and oversight by revenue authorities. These are some of the factors which accelerate research in the use of subcritical water for the extraction of natural products and nutraceutical food We have found that the generic solvation properties of the components. This aids in considering the widespread utilization of two principal critical fluids, CO and water, to be explained by an 2 water and carbon dioxide as a part of the overall critical technology extended solubility parameter approach [7,8]. Hence by adjustment platform [1]. of pressure and temperature for CO , or temperature in the case 2 Traditional oleochemical processing operations such as fat of water, one can optimize the solubility of solutes or reactants in splitting or hydrogenation are often conducted under either sub- these media, or predict their miscibility, by comparing their relative critical or supercritical processes. Fat-splitting processes such as solubility parameters as a function of temperature and pressure. the Twitchell process [12] or Colgate-Emery synthesis [13] uti- Such an approach has a practical value considering the molecular lize temperatures and pressures in excess of the boiling point of complexity of many solute types processed in critical fluids. Their water under the appropriate pressure, but below the critical point solubility parameters or solute–fluid interactions can be explained of water to facilitate the hydrolysis of triglycerides to fatty acids. by using the Hansen three-dimensional solubility concept which However, it should be noted that these processes were frequently allows the application of functional group contribution methods interpreted as steam-based hydrolysis rather than hydrolysis using for calculating requisite physical property data as well as solute or subcritical water. Hydrogenations using binary mixtures of CO2-H2 solvent solubility parameters as recently reported by Srinivas et al. or propane-H2 are supercritical with respect to the pure component [9]. As indicated by Fig. 2, the reduction in water’s total solubility critical constants, but reaction conditions are conducted under less parameter with increasing temperature is largely due to a reduction dense conditions due to the high temperatures involved, and hence in the hydrogen-bonding propensity as reflected by its hydrogen- the cited rapid kinetics associated with hydrogenations conducted bonding solubility parameter component, ı [10]. Water does not H under these conditions [14] refers more to the accelerated mass attain the solvation properties of solvents like ethanol or methanol transfer effects as opposed to reactant solubility enhancement. until quite elevated temperatures which is in contrast to the often Enzymatic-based synthesis under supercritical conditions has been cited dielectric constant concept which is invoked to explain the largely confined to laboratory-scale studies [15–17] and the sensi- solvent properties of subcritical water [11]. tivity of enzymes to operational parameters and their attendant The above solvent properties of water as described by the high cost suggests that their application maybe limited to the syn- solubility parameter concept has some implications with regard thesis of high cost products. to its use as a “green” solvent and as a substitute for ethanol The advantages of coupling processing options using critical in hydroethanolic-based extractions which are GRAS (Generally fluids are illustrated in Fig. 3. Hence by combining different unit Regarded as Safe)-approved food processing solvents. Its substi- processes and sequencing them with the use of multiple fluids tution for ethanol as a processing medium is highly desired to save held at operational densities by the application of different tem- on processing costs, its separation from water in solvent recycle peratures and pressures, one can obtain multiple products and optimize the extraction or reaction process. Several specific options are illustrated for the case of processing essential oils as noted previously in Table 1 [18] using pressurized fluids. Here six discrete unit processes are listed which include standard SFE with SC-CO2,

Table 1 Coupled processing options for essential oils processing using pressurized ﬂuids

Process

(1) SFE (SC-CO2) (2) SFF (SC-CO2)—Pressure reduction (3) SFF (SC-CO2)—Column deterpenation (4) SFC (SC-CO2/co-solvent) (5) SFF—(subcritical H2O deterpenation (6) SFM—(aqueous extract/SC-CO2)

Processing combinations (1) + (2) (1) + (2) + (3) (1) + (4) (1) + (5) Fig. 2. Three-dimensional solubility parameters of water as a function of tempera- (1) + (5) + (6) ture. 600 J.W. King, K. Srinivas / J. of Supercritical Fluids 47 (2009) 598–610

SFF (supercritical fluid fractionation) employing stage-wise pres- diffuse focus on using water in its subcritical state with respect to sure reduction, SFF as practiced using column-based deterpenation its. Tc received attention due to its application as a reaction medium [19], supercritical fluid chromatography (SFC), another variant of to transform organic chemicals and biomass into targeted products SFF called subcritical water deterpenation [20], and utilization of [26,27]. Concurrently in the field of analytical chemistry, subcriti- a SC-CO2 or LCO2 with a perm selective membrane described by cal water and other subcritical fluids were explored as alternative Towsley et al. [21]. As shown in Table 1, combinations of these pro- extraction solvents under external compression above their boil- cesses can allow a total processing scheme to be conducted using ing points [28–30]. Analytical methods developed with the use of critical fluids. For example, a combination of processes (1) and (2) pressurized solvents essentially use subcritical fluids above their in Table 1 could be combined to yield a more specific composition boiling point—the pressure applied frequently is far in excess of in the final extract. Unit process (1) if conducted by sequentially what is required by inspection of the V–L curves for these fluids [31]. increasing the extraction density when coupled with a sequence Unfortunately researchers in these disparate areas using water as a of let down pressures (unit process 2) can amplify the SFF effect. common compressed fluid have not always recognized its generic Likewise, by combining unit process (1) using SC-CO2 followed by utility as a universal compressed fluid medium as well as “green” application of unit process (2) utilizing subcritical H2O to deterpe- complimentary solvent to compressed CO2 [7]. nate the extract from unit process (1), will yield a more specific Recently we have attempted to explain the solvent charac- final product from the starting citrus oil. To obtain a more enriched teristics of water using an extension of the solubility parameter and/or concentrated product from the latter process, one could add concept, i.e., a three-dimensional solubility parameter approach, unit process (6), a supercritical fluid membrane-based separation by applying it to pressurized water [8,9]. Using the Hansen three- of the aqueous extract/ractions from unit process (5) as indicated dimensional solubility parameter approach coupled with SPHERE in Table 1. and Hsp3D [32] software programs, we have studied the interaction We shall discuss several other combinations of unit processes between subcritical water and complex organic solutes, including and fluids below based on both our research and those of others biopolymers, as a function of temperature. Water under compres- cited in the literature. Many of these examples are focused on the sion has the ability by adjustment of the applied temperature processing of complex natural product mixtures, lipids and oleo and pressure to serve as an extraction solvent as well as a reac- chemicals, and more recently the processing of biomass for value- tion medium depending on what is desired. Residence time of the added extractives and conversion to fuel substrates, since we are solute (reactant) in the aqueous medium thus becomes a criti- most familiar in applying critical fluids in those areas. cal parameter in conducting extractions above the boiling point of water and for optimizing reaction conditions “higher up” the 2. Multiple critical fluid processing platforms V–L curve for water. There appears in our opinion the lack of ratio- nale design for choosing reaction conditions in subcritical water, In the broadest sense, multiple critical fluid processing involves although the semi-empirical “severity” parameter often-cited in the integration of two or more fluids held under pressure applied biomass conversion studies is one attempt to quantify the required as either mixtures or in a sequential manner for one or more unit hydrolytic conditions [33]. Using a simple solubility parameter processes. Listed in Table 2 are the most prevalent combinations approach, as depicted in Fig. 4, in which the solubility parame- that have been utilized or have potential application in process ter for water as a function of temperature is plotted along with the solubility parameters for cellulose oligomers (n = 1–10), it can development. Solubility of solutes and reactants in SC-CO2 has been extensively studied and a recent tome has assembled much of the be seen that the intercept between the solvent and the cellulose available data [22]. Likewise there is a fair understanding as to the oligomers corresponds to the chosen conditions for depolymeriz- ing the carbohydrate polymers [7]. This confirms that conditions are choice of a suitable co-solvent to pair with SC-CO2 to enhance the commensurate with those in which the biopolymer is dissolved or solubility of more polar solutes in the compressed CO2 medium, although binary phase equilibria data is not always available over miscible in the subcritical water medium. We have also used this the desired range of pressure–temperature for such systems. This is approach for other biopolymers treated in subcritical water such as critical if one is concerned with operating in the one phase super- hemicellulose and chitin and rationalized the difficulty in dissolv- critical fluid region with respect to both components, however as ing lignin-type polymers in subcritical water [7]. A similar approach noted by several investigators [23–25], there are several examples also has utility in understanding the subcritical water extraction where processing can be done with SC-CO2–co-solvent systems in the two phase region. This situation becomes of interest particularly when large amounts of an organic co-solvent are used in conjunction with SC-CO2 to enhance the solubilization of a solute which exhibits limited solubility in neat SC-CO2. The critical ques- tion then becomes whether another compressed fluid might better be integrated into the design of the process. As remarked previously, compressed water at high temperatures and pressures, i.e., supercritical water has been extensively investigated for many years. In the 1990s’ a similar but somewhat more

Table 2 Multiple critical ﬂuid processing options

Mode Example

Single ﬂuid Carbon dioxide, water Single ﬂuid + co-solvent Carbon dioxide + ethanol

Binary gases above their Tc Carbon dioxide + hydrogen Single ﬂuid + dissolved gas Water + carbon dioxide Fig. 4. Solubility parameter variation for subcritical water at different reduced pres- Sequential ﬂuids Carbon dioxide, then water sures pr and cellulose oligomers (n = 1–10) with temperature. J.W. King, K. Srinivas / J. of Supercritical Fluids 47 (2009) 598–610 601

Fig. 6. Variation of Hansen three-dimensional solubility parameter sphere of cyanidin-3-O-glucoside with subcritical water and ethanol at different tempera- Fig. 5. Variation of Hansen three-dimensional solubility parameter sphere of betulin tures. with subcritical water and ethanol at different temperatures. of target solutes from natural product matrices, such as silymarins ring to the compounds outside the Hansen solubility sphere. The from milk thistle, B-vitamins from brewers yeast, and anthocyanins inverted white triangle on the other side of the center of the mass from grape pomace. of the sphere is the solute itself. The Hansen three-dimensional sphere method noted above One study we have contributed to involves the extraction of can also be used in choosing a subcritical fluid as an extraction betulin from birch bark extracts using subcritical water or ethanol solvent and optimizing the extraction conditions. The three- as solvents. The experiments were conducted using subcritical dimensional solubility parameters of water and ethanol at a water maintained at 40–180 ◦C and 5 MPa using an analytical-based reference temperature (25 ◦C) are obtained from Hansen [32] and extraction system. It was found that a limited amount of betulin their temperature-dependence calculated using the approach of was extracted into subcritical water even at temperatures as high as Williams [34]. The Hansen spheres were then generated using the 180 ◦C. However, similar studies conducted with subcritical ethanol Hsp3D program in a Matlab platform. The inverted white trian- yielded high amounts of betulin at 90 ◦C and 5 MPa [35]. The three- gles which appear in Figs. 5 and 6 below indicate that the targeted dimensional solubility parameter Hansen sphere plots for betulin in solute is within the solubility sphere thereby ensuring high misci- water and ethanol respectively are shown in Fig. 5. Here the radius bility with the subcritical fluid, while the dark triangles indicate of the Hansen sphere for the betulin–ethanol system is far less than immiscibility between the solute and the subcritical fluid refer- that observed for the betulin–water system. This is indicative of 602 J.W. King, K. Srinivas / J. of Supercritical Fluids 47 (2009) 598–610

centration of nitrogen led to a dramatic reduction in solubility of caffeine in CO2. Similar trends were recorded when helium was added to SC-CO2 for the solubility of soybean oil in SC-CO2. This has important implications for conducting reactions in SC-CO2 since the addition of hydrogen to SC-CO2 permits higher hydrogenation reaction rates to be attained [42], but at the cost of reduced solute solubilities in the more highly compressed supercritical fluid component. Dissolved gases in compressed dense fluids or liquids can have a profound effect on the extraction of solutes from substrate using such modified solvents. So-called “enhanced fluidity modifiers [43] serve as a basis for increased extraction of oils from petroleum reservoirs, analytes absorbed in sample matrices, and in the continuous extraction of vegetable oils from seed meals. Recently, compressed gases in their supercritical fluid state; particularly SC-CO2, dissolved in liquids and subcritical liquids have become of interest as in situ catalysts or modifiers for reaction and Fig. 7. Variation in the Hansen sphere radius (MPa1/2) versus %ethanol in com- extraction unit processing. The use of SC-CO2 as a replacement for pressed water–ethanol extraction solvent. metallic catalysts in glycerolysis reactions was reported by Temelli et al. [44] and a review of its use in synthetic organic reaction chemistry has been published by Rayner et al. [45]. Dissolving SC-CO2 the fact that subcritical ethanol is a far better solvent under the under pressure in pressurized water creates a versatile medium stated conditions than compressed hot water. A further study of the with respect to acidic-based extraction chemistry and reactions due relative energy difference (RED) values for the two solute–solvent to the inherent carbonic acid equilibrium that is pressure depen- systems indicates miscibility–solubility between 50 and 125 ◦Cin dent as studied by Toews et al. [46]. We and others have found that the betulin–ethanol system with a maximum betulin solubility if sufficient CO2 under pressure is applied to aqueous solutions, occurring at 100 ◦C [9]. that pH’s between 2.0 and 2.5 can be achieved. The basis of this Similarly in Fig. 6 are the Hansen spheres for the antho- enhanced dissolution can be seen from the literature data that we cyanin, malvidin-3-O-glucoside, in water and ethanol, respectively. have plotted in Fig. 8 [47–50]. Intuitively, increasing the tempera- The sphere plots indicate a greater miscibility of malvidin-3- ture of water should decrease the amount of gas dissolved in water O-glucoside in ethanol since the Hansen sphere has a lower as borne out by the data taken at lower pressures and temperatures radius (7.23 MPa1/2) in the temperature range of 25–75 ◦C. For the shown in Fig. 8, however application of greater pressure as applied water–malvidin-3-O-glucoside system, the corresponding solubil- to SC-CO2 lowers the pH of the solution due to an increase in the ity sphere occurs over a different temperature range and a RED amount of dissolved gas in water (Fig. 8). Our research group and radius of 10.35 MPa1/2, higher than that for ethanol [8]. While both others have recently exploiting this trend to assist in the conversion subcritical solvents dissolve the target anthocyanin at different con- of various types of carbohydrate-laden biomass by converting the ditions, clearly ethanol would be the preferred subcritical solvent constituent carbohydrate polymers to lower oligomers for even- with respect to anthocyanin miscibility and solubility. tual conversion to biofuels. Similarly control of solution pH by The three-dimensional solubility parameter sphere approach dissolution of SC-CO2 can also affect the equilibrium-based species can also be used to explain experimental results we have obtained that is extracted when using subcritical water as is the case for for the solubility and extraction of malvidin-3-O-glucoside in anthocyanins and similar flavonoid-based solutes [51]. This tech- compressed-hydroethanolic solvent medium. The Hansen solubil- nique offers definite advantages with respect to avoiding the use ity spheres were plotted for water–ethanol mixtures and their of mineral acids in extraction and reaction chemistry since the dis- corresponding interaction radii versus the composition of subcrit- solved SC-CO2 can be jettisoned to the atmosphere or recycled by ical water–ethanol mixture is shown in Fig. 7. The plot shows a reduction in pressure. Studies using supercritical carbon dioxide an initial substantial decrease in the interaction radius between as reaction solvent especially in catalytic hydrolysis as described the anthocyanin and hydroethanolic mixture upon addition of above have also shown good product separation characteristics by 10% ethanol to water (this is due to the substantial decrease in increasing the pressure from 20 bar to as high as 120 bar. Approx- the hydrogen bonding solubility parameter with the addition of imately 90% of the hexanes were successfully separated from the ethanol to water). This is consistent with the enhanced extraction hydrolytic mixture dissolved in supercritical carbon dioxide [52]. recorded for the flavonoid upon addition of ethanol to the extrac- It was remarked previously (Table 2) that it should be possi- tion medium. Note that although in Fig. 7 the minimum interaction ble to use one critical fluid at different temperatures and pressures radius occurs at 80% ethanol concentration, there is not a signif- to perform multiple unit operations. For SC-CO2, it is well docu- icant difference with that recorded at 10% ethanol content. This mented that changes in the fluid density can be used as a basis has important implications for designing the best extraction condi- for the supercritical fluid-based fractionation (SFF) of a number tions and minimizing the amount of co-solvent (ethanol) required of complex mixtures. This is also possible in the case of subcrit- in extracting the target flavonoid. ical water, but usually through the adjustment of temperature. The use of compressed gases at conditions far above their crit- As the authors have previously noted, hot compressed water is ical temperature as diluents in a highly compressed supercritical a versatile medium in both its sub- and supercritical regions by fluid such as SC-CO2 has been studied by several groups [36–38]. using it over a range of reduced temperatures (Tr) and pressures Such binary mixtures of compressed gases may act as co-solvents (Pr) depending on the unit processing result that is desired. High or antisolvents depending on their Tc’s relative to that of supercrit- values of Tr (1.02–2.5) and Pr (1.2–1.8) are used for destructive ical fluid [39]. Helium and nitrogen have been previously studied schemes, such as supercritical water oxidation, while a lower range as anti-solvents in supercritical fluid extraction of caffeine [40] and of Tr’s and Pr’s are employed for selective molecular transforma- lipids from soybean oil [41]. For the extraction of caffeine when tions such as biomass conversion via specific reaction pathways. using supercritical carbon dioxide as a solvent, increasing the con- Biomass conversion in hot compressed aqueous media embrace J.W. King, K. Srinivas / J. of Supercritical Fluids 47 (2009) 598–610 603

Fig. 8. Mole fraction solubility of CO2 in water as a function of temperature and pressure.

operational parameters (Tr = 0.65–1.05, Pr = 0.35–2.0) in both the process is that it can be potentially conducted in one reactor of sub- and supercritical phases for water The use of subcritical water integrated processing plant therefore saving on capitalization costs. for extractions depends on the physical properties of the dissolved solutes and their tendency to degrade under the chosen extraction 3. Multiple unit processing: concepts and possibilities conditions. For example, Tr’s and Pr’s are typically in the range of 0.50–0.80 and 0.02–0.35, respectively, for the extraction of natural The generic concept of using critical fluids in more than one products. unit process utilizing critical fluids was discussed in Section 1 and Fig. 9 shows a hypothetical multi-unit processing scheme based a pertinent example given. In this section we wish to elaborate on entirely on subcritical water for the treatment of a potential this concept in two ways: (1) coupling critical fluids with an exist- biomass substrate [7]. Here the target substrate is pretreated with ing processing device and (2) coupling unit processes to achieve pressurized water to prepare it for eventual extraction or reac- a final product or end goal. The senior author has noted previ- tion using subcritical water. The pretreatment with pressurized ously that processing with supercritical fluids can consist of an water can be used to swell the substrate or comminute it for extraction mode (SFE), fractionating using supercritical fluids (SFF), more effective extraction or reaction. Using the above criterion, conducting a reaction(s) in critical fluid media (SFR or CFR) and the an extraction can be performed using pressurized water above formation of fine particles in critical fluid media, or CPT. Advances in its boiling point to recover high value botanical extracts from the processing using critical fluids can frequently be achieved by mod- substrate prior to using subcritical water as a reaction solvent. Post- ifying an existing device or concept, such as an expeller or extruder extraction treatment is then performed over a higher temperature ◦ to provide a continuous processing method, or utilize equipment range (150–300 C) to hydrolyze the remaining biomass for further to concentrate or fractionate an initial extract or reaction mixture. conversion to a lower molecular weight hydrolyzate suitable for Here we shall consider two significant advancements utilizing fermentation to a liquid fuel. Partial realization of this scheme will compressed critical fluids with two devices: an expeller with a focus be described further in Section 4. The advantage of the described on seed oil processing and the use of membranes coupled with critical fluids. The concept of continuous processing of oils from seeds and meals goes back to the mid-1980s with the description of the operation of an Auger-type screw press by Eggers [53]. Here a supercritical fluid such as SC-CO2 is used to assist in the removal of oil from crushed seeds or meals which may have been partially pre- extracted. The physicochemical basis of the process is still not well understood, but involves the addition of liquefied CO2 to the seeds or meal inside an expeller barrel to aid in the oil extraction process. The hydraulic compression on the seed meal creates considerable pressure and heat on seed matrix resulting in the conversion of the added CO2 to its supercritical state. The hot compressed carbon dioxide partially solvates the seed oil akin to what occurs when SFE is performed with SC-CO2, but more importantly dilutes or expands the expressed oil enhancing its removal from the seed or meal bed. Methods to achieve this goal have been described Fig. 9. Tandem subcritical water processing of biomass. in the patent literature most notably by Foidl [54] whose process 604 J.W. King, K. Srinivas / J. of Supercritical Fluids 47 (2009) 598–610 has been partially commercialized and applied to the processing of soybeans. This CO2-assisted expression process has been commercialized by Crown Iron Works in Minneapolis, Minnesota under the trademark of HIPLEX process and CO2 expression demonstrated on a Harburg Freudenberger expeller having a 25 ton per day capacity. The process is in commercial operation at SafeSoy Technologies in Ellsworth, Iowa. The ratio of oil to CO2 is 3:1 which reduces the vegetable oil viscosity by 1/10 resulting in between 80 and 90% vegetable oil recovery for soybeans and over 90% recovery of canola oil. Such solvent-free oils and meals are superior in quality to solvent extracted products. A similar device would be welcomed for subcritical water extraction of natural and food-related products as well as for the conversion of biomass substrates on a continuous basis (see Section 4) in which the substrate to be extracted or treated with pressurized water would be contacting as a slurry Fig. 10. Phospholipid enrichment/fractionation using coupled supercritical fluid- with the pressurized water. This could be in principle applied to based processes. such diverse matrices as grape pomace, cocoa beans, and herbal substances provided the residence times above the boiling point of water are minimized. Current systems for affecting such pressur- nanofiltration or reverse osmosis membranes. This system oper- ized water extractions are staged as semi-continuous batch systems ated at a pilot scale between 8 and 15 MPa and at 40 ◦C resulted or by combining the substrate to be processed as aqueous slurry in a maximum yield of polyphenols of 43% when the pressure with water before passage through a heated extraction vessel. It was optimized at 8 MPa using ethanol. The study also indicated a should be noted that critical fluid-based expeller processes com- high performance of all the membranes when the trans-membrane pete with similar unit processing done with the aid of extruders pressure was maintained in excess of 1 MPa [61]. The ability to [55]. Although extruders have shown promise in the processing concentrate extracted polyphenols using SC-CO2 extraction paired of finished food products [56] their attendant expense and lower with membranes suggest that a similar tandem involving sub- throughputs make them less attractive than the expeller-based pro- critical water–membrane coupling would be advantageous since cesses described above. extraction with subcritical water results in a diluted extract. This The second development which we feel is important is the cou- concept was first advanced by King [62] and noted in a US patent pling of critical fluids with membrane technologies. This can be issued to Wai and Lang [63]. They suggested that SFE could be applied in a number of very diverse applications ranging from con- implemented on a natural product matrix followed by subcriti- centrating extracts, providing additional fractionation on extracts cal water extraction sequentially on the same matrix and then derived from SFE using SC-CO2, and as an alternative post-SFE sep- followed by a membrane separator to yield a concentrate of the aration process to avoid the recompression costs associated with aqueous extract. The authors view the actual implementation of phase-based separation methods involving recycle of the supercrit- such tandem technologies as critical to the further development of ical fluid after extraction. In the latter case, Brunner [57] has noted the application of subcritical water extraction for processing food, that since the molecular weight of supercritical fluid is considerably nutraceutical, and natural products. less than the extracted solutes, application of a permselective mem- Countercurrent contacting of a liquid or SC-CO2 stream on one- brane that is compatible with operation at high pressure should be side of a permselective hollow fiber membrane to enrich aroma feasible. Coupling of supercritical fluid extraction processes with components from aqueous solutions may be a way of approach- membrane technology for supercritical fluid recovery and prod- ing the above problem. Sims has demonstrated such a process uct purification can decrease the energy requirements and provide and patented it as the POROCRIT process, and also applied it to fractionation of the extracts or reactants from an extraction and/or the sterilization of citrus juices among other applications [64]. reaction processes. Sarrade et al. [58] has provided a comprehensive Research involving the use of compressed solvents such as carbon review on the integration of these two technologies. dioxide to extract fermentation products like ethanol and ace- Studies have also been conducted to study the performance of tone within a hollow fiber membrane reactor employ a similar different types of reverse osmosis (RO) membranes in recovery of approach. In this study, a membrane fiber made of microporous supercritical carbon dioxide after the extraction of essential oils hydrophobic polypropylene was used in a single fiber membrane from natural products like lemongrass, orange and nutmegs. Essen- contactor and operating conditions maintained at 0.02–0.07 MPa tial oil retention by the membranes was reduced with increase trans-membrane pressure at ambient temperature. For aqueous in the trans-membrane pressure drop but there was no effect binary feed solutions containing 10:10 wt% ethanol: acetone or observed when the oil feed concentration was varied. Recovery of 5:5 wt% ethanol: acetone solution. Recovery of ethanol ranged the essential oils was approximately 90% via this coupled process between 5 and 14% while that for acetone ranged between 68 and [59]. RO membranes were also used for the recovery of carbon diox- 96% depending on the CO2 flow rate using molar solvent to feed ide from limonene extracted from essential oil yielding matrices. ratios between 3 and 10 [65]. The process compared the performance of one nanofiltration and Combing various unit processing options using critical fluids to three RO membranes at identical upstream and trans-membrane achieve an end goal involves looking at a matrix of possibilities and pressures slightly above the Tc of CO2. achieving optimization for all of the combined processes. In our Integrating critical fluid technology with membranes has approach over the past two decades, we and others have investi- permitted the separation of low and high molecular weight gated and optimized the individual unit processes with an overall compounds obtained from the SC-CO2 extraction of lipids from final objective of producing a final result/product—it is less frequent foodstuffs such as butter or fish oil using nanofiltration mem- to find the discrete steps already combined, but examples of both branes [60]. Similarly, it has been reported that is possible to extract will be given in this section and Section 4. Several reviews have been polyphenols from cocoa seeds using neat SC-CO2 and with ethanol published by the senior author regarding coupled processing [18], as a co-solvent, and then concentrate the extract using polymeric its application for nutraceutical [5] and lipid processing [66], and J.W. King, K. Srinivas / J. of Supercritical Fluids 47 (2009) 598–610 605

Table 3 Percentage amounts of PLs in extracts derived from SFE and SFC processing stagesa

Phospholipid type SFE stage SFC stage

Phosphatidylethanolamine 16.1 74.9 Phosphatidylinositol 9.2 20.8 Phosphatidic acid 2.8 55.8 Phosphatidylcholine 15.6 76.8

a Relative to other eluting constituents (oil and unidentified peaks). the use of reaction chemistry for conversion of agricultural materials [1]. Today, production plants and toll refiners in addition to SFE offer one or more other unit processes for the refining of materials, although there is room for more expansion using multiple unit processing. Perrut [67] has recently reported a pilot plant designed for multi-fluid extraction and reactions using either SC-CO2 or subcritical water. Similarly, we have been able to alter bench scale extractor units using booster-type pumps, originally configured for SC-CO2, to allow extractions and reactions to be conducted with subcritical water [68]. Laboratory investigations of potential multiple unit processing with critical fluids is frequently done by investigating one discrete Fig. 11. Production of fatty alcohol mixtures using a (a) SFR–SFR sequential reaction process followed by another, and realizing the potential for arrang- scheme, (b) feedback of methanol into the SFR process and its inherent “greenness”. ing these in a tandem manner to achieve the desired end product. For example, based on several studies focused on the enrichment of a lecithin-phospholipid (PL)-containing fractions from seed oil was based on studies involving the enzymatic synthesis of FAMES extracts [69–72], we have postulated an entire process based on SC- directly from vegetable oils dissolved in SC-CO2 [75,76]. Combin- CO2 with and without co-solvent addition employing SFE followed ing this transesterification reaction with a hydrogenation reaction by displacement supercritical fluid chromatography (SFC) [73] as using consecutively coupled packed bed reactors allowed the pro- shown in Fig. 10. Here soybean flakes are initially extracted with duction of FAMES in either a SC-CO2 or SC-C3H8 stream followed by SC-CO2 to remove the oil from flakes, followed by extraction of the exhaustive hydrogenation of the FAMES to fatty alcohols as shown PLs from the de-oiled flakes with a SC-CO2/ethanol mixture. The in Fig. 11a. In this process, a non-Cr catalyst was used to success- ◦ second extraction step produces an extract enriched in PLs since PLs fully convert the FAMES to the C16 +C18 saturated alcohols at 250 C are not appreciably soluble in neat SC-CO2, but can be selectively and 25 mol% H2 in SC-CO2. This is an excellent example of how a removed from the flake matrix with the aid of ethanol as a co- two-step synthesis process can be conducted in supercritical fluid solvent. As shown in Table 3, the second SFE using SC-CO2/ethanol media that is environmentally benign by permitting the reuse of produces an extract containing a total 43.7% by weight of PLs. This the critical fluid media as well as the reaction by-product from the is a considerable enrichment relative to the concentration of the hydrogenation step, methanol (Fig. 11b). PLs in the starting oil or seed matrix. Further PL enrichment is It is impossible to separate in the multiple unit and fluid pro- facilitated as noted above, by transferring this extract enriched in cessing platform the role of fluid interchange with tandem unit PLs to an alumina preparative SFC column, where SC-CO2 modified processing. Toward this end, the choice of solute or substrate modi- with a 5–30 vol.%, 9:1/ethanol: water eluent is used to elute and fication and/or fluid medium can enhance the opportunity to utilize fractionate the PLs. In the case of the SFC enrichment step, eluent the various combinations of fluids or unit processes. Two will be fractions can be collected as a function of time and their PL content cited here: (1) formation of methyl esters of lipid-type solutes such quantitated. As indicated by the data given in Table 3, collection as fatty acids (FAMES), and (2) use of water primary for hydrolysis of discrete fractions during the SFC process can produce purities in of complex naturally occurring substrates. FAMES are an extremely excess of 75% for the individual PLs, phosphatidylcholine and phos- versatile modification for the critical fluid processing of fats/oils phatidylethanolamine. It should be noted in the described process and their oleo chemical derivatives. Aside from the formation of that in the SFC steps, only GRAS solvents are being used for the FAMES for conversion to biodiesel via enzymatic synthesis [77] or in enrichment process. Recently, a similar SFE/SFC process has been sub- and supercritical methanol [78], FAMES or similar esters can be suggested for isolating sterols and phytosterol esters from corn bran used advantageously in SFE [79], columnar modes of SFF [80], SFC and fiber [74]. [81], and as noted above in SFR. This versatility is due to one or more To justify the above process we have quantified the degree of PL of the following factors relative to the non-methylated analogs: (1) enrichment in terms of the product selling price after each unit pro- enhancement of solute volatility or solubility, (2) improvement of cess. Therefore starting from crude soybean oil at US$ 25–35/lb we separation factor (˛), (3) intermediate formation for downstream can obtain a PL-lecithin-enriched fraction after SFE using ethanol synthesis, and analytically useful derivatives [15]. Formation of as a co-solvent worth US$ 31.00/lb, and subsequently with SFC FAMES before utilizing multi-unit processing can allow easier SFF produce pure phospholipid extracts that retail for US$ 1800/lb. of fatty acids [82], selective SFE and SFR of fatty acids from tall Progress toward the above goal has been partially realized by the oil [83] for subsequent conversion to biodiesel, and to fractionate construction of commercial plants to produce deoiled-lecithin by soapstsock [84] or deodorizer distillate [85]. For example, coun- Uhde and Thar Technologies. tercurrent multistage processing of edible oils using critical fluids The above process is a SFE–SFC binary unit processing scheme. has been shown to be capable of producing fatty acid esters, toco- We have on a lab scale also demonstrated the feasibility of a pherols, squalene, sterols, and triglycerides. Approximately 70% of SFR–SFR sequential set of reactions to make fatty alcohol mixtures. the fatty acid methyl esters in deodorizer distillates plus toco- The generation of fatty acid methyl esters (FAMES) in this case pherols and sterols can be extracted with SC-CO2 [86]. Tocopherols 606 J.W. King, K. Srinivas / J. of Supercritical Fluids 47 (2009) 598–610

cides from ginseng using an upward flow of CO2 while ginseng extracts are concentrated in a downward flow of water using the same SFE vessel. Wai and coworkers [90] have sequentially applied SC-CO2 and then subcritical water for fractionating bioactive components from St. John’s wort. The active components hyperforin ◦ and adhyperforin were partitioned into CO2 at 30 C and 8 MPa resulting in 93–99% recoveries, while hypercin and pseudohyper- cin were subsequently recovered via pressurized water extraction at neutral pH at 80–93% yield. Similarly, the potential and prob- lems of sequential extraction of the South American plant, boldo, first using SC-CO2 with and without ethanolic co-solvent, and then batch-pressurized water extraction were reported by del Valle et al. [91]. The extraction selectivity for the plant essential oil and the boldine alkaloid paralleled their relative solubility in non- polar SC-CO2 and enhancement in the solubility of more polar solutes in CO2 + ethanol mixtures as well as in subcritical water. This study and others involving polyphenolic target solutes, indicate that extractions with subcritical liquids are effective up to a certain extraction temperature, but beyond this temperature, pressurized solvent processing can lead to solute degradation or Fig. 12. Treatment of various types of biomass and mixtures with subcritical water and the resultant products. molecular transformation [92–94]. In the latter cases, this reactiv- ity of the solute in the subcritical liquid maybe viewed as desirable since the free radical scavenging capacity of the resultant extracts and sterols in the resultant extract can then be separated from increase. An example of this trend was reported by the Ibanez group the FAMES by columnar SFF by countercurrent fractionation using in Spain [95,96] for the extraction of rosemary by either SC-CO2 or SC-CO2. subcritical water. Carbon dioxide fractions collected at 10–40 MPa Illustrated in Fig. 12 are a number of potential sequences for and 40–60 ◦C resulted in removal of the essential oil and partial applying subcritical water to pre-fractionated and unfractionated fractionation of the antioxidants from the rosemary matrix, while biomass substrates for the production of fuels and chemicals. subcritical water favored extraction of the more polar bioactive Hydrolysis as illustrated can produce oils or lipids by subcritical compounds such as carnosic acid or resultant fractions having high water extraction followed by SFR to produce free fatty acids (FFA). antioxidant capacity. Likewise, subcritical water on isolated protein fractions (perhaps The above typical results of employing CO2 extraction in tandem by subcritical water extraction) can be used as a time-dependent with pressurized liquid fluids suggest an interesting option and cur- reaction medium to produce protein hydrolyzates, an extended rent trend in employing this mixed pressurized fluid matrix as both SFR to produce peptide mixtures, etc. If one takes unfractionated extraction and reaction media. As noted previously, the incorpora- biomass mixtures, such as a deoiled-protein/carbohydrate fraction, tion of pressurized CO2 into subcritical water, i.e., a gas-expanded and treats it using SFR with subcritical water, mixtures of amino liquid, makes for an interesting extraction and reaction medium. acids, organic acids, and sugars results. While the resultant mixed The Meireles group in Brazil [97,98] have utilized this principle in hydrolyzate might not seem useful it is in actuality a seed mixture the processing of ginger bagasse both as a pre-treatment step and for the eventual fermentation production of biomethane, since the to degrade bagasse to sugars for potential fermentation. Pretreat- resultant hydrolyzate can be treated with methanogenic bacteria ment with SC-CO2 seemed to yield somewhat ambiguous results to produce a mixture of CO2 and CH4 [87]. since the authors state that non-treated bagasse was hydrolyzed more effectively then CO2-pretreated bagasse [99]; the latter pro- 4. Examples of integrated critical fluid processing cess was hypothesized to degrade the oleoresinous materials in the bagasse matrix. Their results for matrix pretreatment with SC- There are numerous examples of multi-fluid and -unit process- CO2 are in stark contrast with other reports in the literature that ing but they can be crudely classified into several generic groups. indicate SC-CO2 pretreatment is an effective procedure preced- Processing using one critical fluid offers the opportunity to mix SFE, ing biomass degradation [100]. It should be noted that the above SFF and SFR processes as has already been amply illustrated. The results are somewhat different then using the previously men- most versatile combination seems to be using two fluids, namely tioned carbonated water to hydrolyze carbohydrate polymers; also SC-CO2 and pressurized water. Using subcritical water, Smith et al. SC-CO2 is effective in removing high value components from the [88] have shown that the “green” processing of cashew nuts is pos- biomass matrix prior to hydrolyzing the biomass matrix [99]. Since sible; SC-CO2 being used for the recovery of the cashew nut shell reported SC-CO2 pretreatment methods exist and carbonated water oil containing the pharmacological-active alkenyl phenolic com- hydrolysis has been shown by us [101] and others [102] to be an pounds. The cashew nut shells were initially treated with carbon effective hydrolysis medium, the above ambiguity may be due to dioxide at 40 MPa and 100 ◦C using successive depressurization the varying recalcitrance of the target biomass matrix to hydrolytic steps to accelerate to remove 95% of the cashew nut shell liquid. degradation. The hydrolytic action patterns of carbonated water can After SC-CO2 extraction, the residual shell biomass can be rapidly vary quite significantly depending on the matrix being hydrolyzed dissolved (5 min) in pressurized high temperature water (410 ◦C) although the hydrolysis temperature and residence time can be suggesting that hydrolytic-based gasification of remaining shell varied to produce optimal depolymerization of the carbohydrate material would be suitable for fuel purposes. polymers inherent in the biomass. Numerous research groups are now practicing tandem SC- One aspect of our current research focuses on the application of CO2–subcritical water extraction using different approaches. critical fluids for processing grapes and grape by-products and sim- “Hybrid” SFE with CO2 and water has been applied to a wide variety ilar natural antioxidant-containing matrices. These matrices and of natural product matrices [89] such as the separation of pesti- target solutes are a fruitful area in which to apply combinations J.W. King, K. Srinivas / J. of Supercritical Fluids 47 (2009) 598–610 607 of mixed critical fluid and unit processing steps. One of the sem- inal questions is whether SC-CO2 and co-solvent combinations or a hot pressurized fluid such as water or ethanol – or combinations thereof – are most appropriate for extracting and fractionating the targeted solutes. There is a considerable literature in the application of SC-CO2 for extracting grape seed oil [103,104] as well as further fractionating the extract to enrich certain polyphenolic constituents. Recovery of solutes such as gallic acid, catechin, epicatechin, etc. via a SC-CO2-based method almost always require the use of methanol or ethanol as co-solvents [105]. Other studies have utilized subcritical water to extract procyanidin compounds and catechins from grape processing wastes [106]. Extractions conducted at approximately 10 MPa and in the temperature range of 50–150 ◦C were adequate to recover and fractionate gallic acid, procyanidin dimers, and the corresponding oligomers from the grape pomace using an analytical scale pressurized fluid extractor (ASE). Aside from water and hydroethanolic pressurized fluid extraction, sulfured water has also been proven effective for the extraction of anthocyanins and procyanidins from grape pomace [94]. This parallels similar work by the senior author in using neat and acidified water to extract anthocyanins from berry substrates using both ASE and a batch continuous subcritical water extractor. As noted in the patent issuance on this process [107], residence time of the extracted solute in the hot pressurized water must be minimized to prevent degradation of the anthocyanin moieties or their possible reaction with sugars to other products. It is unknown at this time whether such side reactions in pressurized water could be generating antioxidant moieties, but the potential ability to control the ratio of polyphenolic stereoisomers and to depolymerize or repolymerize biologically active antioxidant oligomers in pressurized fluid media could be a significant area for future research—particularly if they come from cheap and renewable natural resources [8]. In concluding this section it is worth considering far more ranging applications of the critical fluid technology platform that Fig. 13. The Saka-Danan two-step SFR process incorporating both subcritical water embrace the multi-fluid and -unit processing as discussed above hydrolysis and supercritical methanolysis of fats/oils to produce biodiesel. for the industrial production of chemicals, fuels, etc. The authors have previously noted the considerable potential for applying crit- be further treated with the aid of sub- and supercritical fluids to ical fluids in biorefineries, etc. [7] but several existing examples are produce biogas. worth citing. Kusdiana and Saka [108] have demonstrated a two- Baig et al. [111] have recently reported on the combined critical step process for the production of biodiesel (see Fig. 13b) based fluid treatment of sunflower oil to yield value-added substances as on the Saka—supercritical methanol process (Fig. 13a) for convert- well as a model for the “critical fluid biorefinery”. This concept can ing both fats/oils and free fatty acids to biodiesel. The Saka-Dadan be achieved by coupling two or more reaction processes into one process uses subcritical water in front of the Saka process for the continuous flow system; namely the subcritical water hydrolysis hydrolysis of fats/oils to free fatty acids followed by a more benign of sunflower oil triglycerides to free fatty acids followed by ester- supercritical methanolysis of the resultant free fatty acids to FAMES. ification of the free fatty acids to FAMES in SC-CO2 using lipase A pilot scale unit of this process is in operation in Fuji City, Japan. catalysis. The subcritical water extractor conditions were main- This overall biodiesel production platform is an excellent example tained at 250–390 ◦C with pressures as high as 10–20 MPa using of having a critical fluid-based SFR–SFR integrated process. oil:water ratios of 50:50 and 80:20 (v/v). The supercritical fluid More recently Brunner and colleagues [109,110] have demon- enzymatic-based esterification process was operated at tempera- strated an integrated critical fluid-based process for the production tures 40–60 ◦C using a Novozyme enzyme catalyst. The subcritical of several chemicals from rice bran. Although studied in discrete water studies indicated a high rate of conversion at higher temper- steps, the foresight of this effort towards developing an integrated atures (330 ◦C) followed by possible degradation of the free fatty critical fluid processing scheme is impressive. Rice bran is ini- acids when exposed to longer residence times. A yield of approx- tially deoiled using SC-CO2 at the appropriate extraction conditions imately 90% hydrolyzed free fatty acids was achieved in 25 min at resulting in defatted rice bran. This substrate is then subjected to 330 ◦Corfor45minat310◦C. The esterification process yielded subcritical water hydrolysis at approximately 250 ◦C to partially between 60 and 70% FAMES at a pressure of 20 MPa and 60 ◦C with pretreat and depolymerize the rice carbohydrate lignocellulosic low enzyme concentrations. polymers to lower oligomers. Final conversion of the subcritical water hydrolyzate to glucose and xylose is accomplished with a 5. Concluding remarks mixed enzyme cocktail for subsequent fermentation conversion to bioethanol. The resultant 5–10% aqueous ethanol mixture from fer- In this document we have attempted to offer our perspective mentation is then multi-staged contacted counter currently with of the current state of integrated critical fluid processing. It is SC-CO2 to yield 99.8% pure ethanol. It is envisioned that non- the author’s opinion that a positive future exists for combining fermentable residues left over from the hydrolysis process could our existing knowledge and studies involving discrete fluids and 608 J.W. King, K. Srinivas / J. of Supercritical Fluids 47 (2009) 598–610

Fig. 14. Process flow diagram for integrated carbonated water pretreatment process for bioethanol production. unit processes done under critical fluid conditions. This will partly a high pressure aqueous medium for pretreatment and hydroly- require “thinking outside the box” in terms of how industrial high sis. The pictured process flow diagram is similar to that reported pressure processing facilities are constructed and by realizing that for current bioethanol production however the addition of acid for the costs inherent in the core pumping, liquefaction, and compres- hydrolysis has been eliminated as well as the corresponding neu- sion facility can serve more than just one purpose, i.e. SFE, and can tralization agent and the attendant use of gypsum as a neutralizing be applied with more than just one critical fluid medium. agent. Note that in Fig. 14, lignin is separated and used as boiler fuel. Over the past twenty years the senior author has on more than However it should be possible to treat lignin at higher pressures one occasion been queried on the possibility of constructing a SFE and temperatures with sub- or supercritical fluid water reaction plant in close proximity to an alcoholic fermentation facility that to also produce valuable carbochemicals [7]. Such a critical fluid- produces high purity CO2 as a by-product. This would seem logi- based processing concept supports the use of renewable resources, cal since the opportunity to apply SFE for vegetable or specialty oil a sustainability platform, and does so in a “green” environmentally extraction could be facilitated with this source of CO2 as well as any benign manner. of the above mentioned CO2-based unit processes. The production also of ethanol at such a site facilitates a preferred co-solvent for Acknowledgments coupling with CO2 as documented previously. Today in the renewable bioenergy field it is envisioned to build coexisting bioethanol We should like to thank Dr. Charles Hansen of Horsholm, Den- and biodiesel production capabilities at the same site. Hence based mark for guidance in the use of the extended solubility parameter on our discussion above, this suggests the possibility of extending concepts presented in the cited associated software programs. Mr. the application of critical fluids platform for the production of these Thomas Potts is acknowledged for preparing some of the graphics two renewable fuels as documented above. Similarly, it was noted that appear in this manuscript. Our collaboration with Professor above that SC-CO2 could be mixed advantageously with pressurized Luke Howard of the Department of Food Science, University of water for extraction and reaction chemistry. Arkansas is also gratefully acknowledged. Fig. 14 shows a hypothetical process flow diagram for an integrated carbonated water pretreatment process for bioethanol References production. Here the process flow diagram illustrates not only the sequence of operations associated with a modified carbon- [1] J.W. King, Sub- and supercritical fluid processing of agrimaterials: extraction, ated water pretreatment–bioethanol production plant, but also fractionation and reaction modes, in: E. Kiran, P.G. Debenedetti, C.J. Peters the elimination of several processing steps required in current (Eds.), Supercritical Fluids: Fundamentals and Applications, Kluwer Publish- ers, Dordrecht, The Netherlands, 2000, pp. 451–488. bioethanol production practice. Also illustrated are the feedback [2] M.A. McHugh, V.J. Krukonis, Supercritical fluid extraction: Principles and Prac- loops from the CO2 production from the fermentor as well as tice, second ed., Butterworth-Heinemann, Boston, MA, USA, 1994. [3] M. Valcarcel, M.T. Tena, Applications of supercritical fluid extraction in food decompression of CO2 after the carbonated pretreatment stage. analysis, Fresenius J. Anal. Chem. 358 (1997) 561–573. Note that the CO2 can be recovered and fed back to the CO2 storage [4] J.W. King, Critical fluid technology for the processing of lipid-related natural vessels, then recombined with water and pressurized to provide products, C.R. Chimie 7 (2004) 647–659. J.W. King, K. Srinivas / J. of Supercritical Fluids 47 (2009) 598–610 609

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