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(12) United States Patent (10) Patent No.: US 6,573,063 B2 Hochman (45) Date of Patent: *Jun

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(12) United States Patent (10) Patent No.: US 6,573,063 B2 Hochman (45) Date of Patent: *Jun USOO6573063B2 (12) United States Patent (10) Patent No.: US 6,573,063 B2 Hochman (45) Date of Patent: *Jun. 3, 2003 (54) METHODS AND SYSTEMS FOR ASSESSING (56) References Cited BIOLOGICAL MATERIALS USING OPTICAL AND SPECTROSCOPIC DETECTION U.S. PATENT DOCUMENTS TECHNIQUES 4,284,355. A 8/1981 Hansen et al. .............. 356/335 4,736,307 A 4/1988 Salb ........................... 364/518 (75) Inventor: Daryl W. Hochman, Bahama, NC (US) (List continued on next page.) (73) Assignee: Cytoscan Sciences, LLC, Seattle, WA (US) FOREIGN PATENT DOCUMENTS (*) Notice: Subject to any disclaimer, the term of this WO 2OOOO37616 12/1999 .................. 435/29 patent is extended or adjusted under 35 U.S.C. 154(b) by 0 days. OTHER PUBLICATIONS Hochna, Daryl W. et al., “Dissociation of Synchronization This patent is Subject to a terminal dis and Excitability in Furosemide Blockade of Epileptiform claimer. Activity,” Science, vol. 270, pp. 99-103 (Oct. 6, 1995)0. Haglung, Michael M., M.D. et al., “Enchanced Optical (21) Appl. No.: 10/001,366 Imaging of Human Gliomas and Tumor Margins,” Neuro (22) Filed: Oct. 30, 2001 Surgery, vol. 38, No. 2, pp. 308-317 (Feb. 1996). (65) Prior Publication Data (List continued on next page.) US 2002/0055092 A1 May 9, 2002 Primary Examiner Louise N. Leary (74) Attorney, Agent, or Firm-Ann W. Speckman; Janet Related U.S. Application Data Sleath (63) Continuation-in-part of application No. 09/629,046, filed on (57) ABSTRACT Jul. 31, 2000, now Pat. No. 6,319,682, which is a continu ation of application No. 09/326,008, filed on Jun. 4, 1999, now Pat. No. 6,096.510, which is a continuation-in-part of Optical detection techniques for the assessment of the physi application No. 08/949,416, filed on Oct. 14, 1997, now Pat. ological State, health and/or viability of biological materials No. 5,976,825, which is a continuation of application No. are provided. Biological materials which may be examined 08/539,296, filed on Oct. 4, 1995, now Pat. No. 5,902,732. using Such techniques include cells, tissues, organs and (60) Provisional application No. 60/088,494, filed on Jun. 8, Subcellular components. The inventive techniques may be 1998. employed in high throughput Screening of potential diag (51) Int. Cl............................. C12O 1/02; C12O 1/00; nostic and/or therapeutic agents. C12O 1/24 (52) U.S. Cl. ............................... 435/29; 435/4; 435/30; 19 Claims, 11 Drawing Sheets 435/288.7; 435/32; 435/968 (58) Field of Search ................................ 435/29, 4, 30, 435/288.7, 32, 968 (2 of 11 Drawing Sheet(s) Filed in Color) isioxirag RCSE: $88:88 $EEE 8 S.E. is: X 68: US 6,573,063 B2 Page 2 U.S. PATENT DOCUMENTS Verkman, A.S., “Optical Methods to Measure Membrane 4,768,513 A 9/1988 Suzuki ....................... 128/634 Transport Processes.” The Journal of Membrane Biology, 4,972,331 A 11/1990 Chance ............. ... 364/550 vol. 148, pp. 99–110 (1995). 5,162,204 A 11/1992 Matsuzaki et al. ............ 435/29 Echevarria, Miriam et al., “Optical Measurement of Osmotic 5,215,095 A 6/1993 Macvicar et al. ........... 128/665 Water Transport in Cultured Cells,” J. Gen. Physiol., vol. 99, 5,270,173 A * 12/1993 Yonemori et al. ............ 435/29 5,369.469 A 11/1994 Alfano et al. ............... 356/446 pp. 573-589 (Apr. 1992). 5,413,108 A 5/1995 Alfano ....................... 128/665 Newell, D.W. et al., “Glutamate and Non-Glutamate Recep 5,438,989 A 8/1995 Hochman et al. ........ 128/653.1 tor Mediated Toxicity Caused by Oxygen and Glucose 5,465,718 A 11/1995 Hochman et al. ........ 128/653.1 Deprivation in Organotypic Hippocampal Cultures,” The 5,507,287 A 4/1996 Palcic et al. ...... ... 128/633 5,580,748 A 12/1996 Alkon et al. .................. 435/29 Journal of Neuroscience, vol. 15, No. 11, pp. 7702-7711 5,585,401. A 12/1996 Bandt et al. ................ 514/562 (Nov. 1995). 5,605,811 A * 2/1997 Seubert et al. ................ 435/29 Barth, A. et al., “Optical Imaging of Acute Ischemic Injury 5,699,798 A 12/1997 Hochman et al. 128/653.1 in Hippocampal Slice Cultures,” Society for Neuroscience, 5,706,821 A 1/1998 Matcher et al. ...... ... 128/665 5,713,352 A 2/1998 Essenpreis et al. ......... 128/633 vol. 22, p. 1424, S. 560.9, (1996). 5,807.261 A 9/1998 Benaron et al. ..... ... 600/473 Barth et al., Optical Imaging of Acute Iscemic Injury in 5,840,035 A 11/1998 Heusmann et al. ......... 600/477 Hippocampal Slice Cultures (Abstract), Society for Neuro 5,845,639 A 12/1998 Hochman et al. .... 128/653.1 scienccle, vol. 22, p. 1424, 1996. 5,854,851 A 12/1998 Bamberger et al. ......... 382/132 5,855,205 A 1/1999 Papaionnou ...... ... 128/664 Hochman, Intrinsic Optical Changes in Neuronal TiSSue, 5,865,738 A 2/1999 Morcos et al. .... ... 600/365 Neurosurgery Clinics of North America, vol. 8, No. 3, p. 5,866,074 A 2/1999 Chapman et al. 422/82.09 393, Jul 1997. 5,902,732 A * 5/1999 Hochman .................... 435/29 5,976,825. A 11/1999 Hochman .................... 435/29 Hochman et al., Dissociation of Synchronization and Excit 6,096,510 A 8/2000 Hochman .................... 435/29 ability in Furosemide Blockade of Epileptiform Activity, 6,319,682 B1 11/2001 Hochman .................... 435/29 Sciente, vol. 270, p. 99, Oct. 6, 1995. OTHER PUBLICATIONS Echevarria et al., Optical Measurement of Osmotic Water Haglund, Michael M., M.D. et al., “Enhanced Optical Imag Transport in Cultured Cells, J. Gen. Physiol., vol. 99, p. 573, ing of Rat Gliomas and Tumor Margins,” NeuroSurgery, vol. 1992. 35, No. 5, pp. 930-941 (Nov. 1994). Verkman, Optical Methods to Measure Membrane Transport Haglund, Michael M., M.D. et al., “Optical imaging of Processes, J. Membrane Biol., vol. 148, p. 99, 1995. epileptiform and functional activity in human cerebral cor Nicholson et al., Hindered Diffusion of High Molecular tex,” Nature, vol. 358, No. 20, pp. 668–671 (Aug. 1992). Weight Compounds in Brain Extracellular Microenviron Hochman, Daryl W., PhC, “Intrinsic Optical Changes in ment Measured with Integrative Optical Imaging, Biophysi Neuronal Tissue,” NeuroSurgery Clinics of North America, vol. 8, No. 3, pp. 393-412 (Jul. 1997). cal Jouniral, vol. 65, p. 2277, 1993. Snow, Robert W. et al., “Electrophysiological and Optical Guggino et al. CA:103:102292; J. Gen. Physiol. 86(1): Changes in Slices of Rat Hippocampus During Spreading 31-58, 1985.* Depression,” Journal of Neurophysiology, vol. 50, No. 3, pp. 561-572 (Sept. 1983). * cited by examiner U.S. Patent Jun. 3, 2003 Sheet 1 of 11 US 6,573,063 B2 S::::::: & pitcESSENGEAR 8ARE i8 our 33333xxxx 33: Cii. iroir > is 88 A. A. U.S. Patent Jun. 3, 2003 Sheet 2 of 11 US 6,573,063 B2 8 FiRSExig ro- w8 WAS --- Patent Jun. 3, 2003 Sheet 3 of 11 US 6,573,063 B2 U.S. Patent Jun. 3, 2003 Sheet 4 of 11 US 6,573,063 B2 A2, 6-1 U.S. Patent Jun. 3, 2003 Sheet S of 11 US 6,573,063 B2 -o-o-o-o-o:OX ------ BOX 4 S.SECR O.OO 20.00 40.OO 6O.OO 80.00 A2. 46 SECONDS 0-0-9-e-eBOX 1 -o-o-o-o-o- BOX 2 0.04 0.02 O.OO 2O.OO 4.O.OO 6O.OO 8OOO A2, 42 SECONDS U.S. Patent Jun. 3, 2003 Sheet 6 of 11 US 6,573,063 B2 A 12 A 2 A2 C2 A2 1/ A2, Aa? Age. CY U.S. Patent Jun. 3, 2003 Sheet 7 of 11 US 6,573,063 B2 Az. off /a, 62. A 6C /2, 62 a 64 a 67 ve. a6 a 6// U.S. Patent Jun. 3, 2003 Sheet 8 of 11 US 6,573,063 B2 A Z-1 /& 75 /& 7C /2, Zo A. Z. Ag. 7 A2, 767 A., 77 U.S. Patent Jun. 3, 2003 Sheet 9 of 11 US 6,573,063 B2 A2, 81/ A2, 8-12 A 81 U.S. Patent Jun. 3, 2003 Sheet 10 of 11 US 6,573,063 B2 - - - 1 - 2 - - - 3 - - - - - - 4. TIME (EACH DIV = 2 SEC) A2, 24 i TIME (EACH DIV = 2 SEC) A2, 22 U.S. Patent Jun. 3, 2003 Sheet 11 of 11 US 6,573,063 B2 A2. /(24 A. MA A. MøC Az /ZZO US 6,573,063 B2 1 2 METHODS AND SYSTEMS FOR ASSESSING In spite of the availability of numerous targets for drug BIOLOGICAL MATERIALS USING OPTICAL discovery, the overall Success rate of the proceSS remains AND SPECTROSCOPIC DETECTION abysmally low. At present, it is fair to say that the question TECHNIQUES How does one apply information about gene and gene products to the discovery of new drugs remains largely REFERENCE TO RELATES APPLICATIONS unanswered. There are three main reasons for low Success This application is a continuation-in-part application of rates in the conversion of vast amounts of genomics infor U.S. patent application Ser. No. 09/629,046, filed Jul. 31, mation to viable products: (1) lack of clear criteria for target 2000, now U.S. Pat. No. 6,319,682 issued Nov. 20, 2001, validation; (2) hits to leads decisions based on potency and which is a continuation of U.S. patent application Ser. No. Selectivity against molecular targets, with limited physi 09/326,008, filed Jun. 4, 1999, now U.S. Pat. No.
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