IP Library Granted Patent US 12,372,440
Granted Patent B2
US 12,372,440 · App. 18/336,855 · Granted Jul 29, 2025

Automated microdissection instrument and method for processing a biological sample

Inventors: Thomas Baer (Mountain View, CA); Craig Barker (San Carlos, CA); Brian Donovan (San Jose, CA); Michael Youngquist (Palo Alto, CA); Alan Wessel (Mountain View, CA); Norbert Leclerc (Heidelberg, DE); Michael Smith (Carlsbad, CA); George Dawson (Santa Clara, CA)
Assignee: Life Technologies Corporation
G01N1/2813G01B11/002G01N2001/282G01N2001/284Y10T156/10Y10T156/1054
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Quick Facts
Patent No.
US 12,372,440
App. No.
18/336,855
Granted
Jul 29, 2025
Kind
B2
Abstract

Systems and methods for automated laser microdissection are disclosed including automatic slide detection, position detection of cutting and capture lasers, focus optimization for cutting and capture lasers, energy and duration optimization for cutting and capture lasers, inspection and second phase capture and/or ablation in a quality control station and tracking information for linking substrate carrier or output microdissected regions with input sample or slide.

Claims (30)

1. A digital microscope comprising:

a worksurface for receiving a sample; the worksurface intersecting a primary optical axis of the microscope;

a substrate receiving location on the worksurface for receiving a sample-bearing substrate; the worksurface having a first opening in the substrate receiving location for alignment with the primary optical axis to permit pathing of light through the first opening in the worksurface;

a digital image acquisition system including an image sensor configured to:

automatically detect the presence of the substrate in the substrate-receiving location; and

automatically record a static image of the substrate to create a roadmap image of the sample after the presence of the sample-bearing substrate is detected in the substrate-receiving location; and

at least two laser sources including an infrared capture laser source and an ultraviolet cutting laser source;

a computer coupled to the digital image acquisition system and the at least two laser sources,

wherein the digital microscope is mounted on a frame and wherein the frame carries the components of the digital microscope,

wherein the capture laser source and the cutting laser source are integrated into the digital microscope being mounted on the frame,

wherein the worksurface includes a staging area for receiving transfer film carriers and/or cap cassettes,

wherein cell capture is performed in the substrate receiving location,

wherein the worksurface further includes a quality control station location, wherein the quality control station location includes an opening in the worksurface that permits illumination and laser light to pass, and

wherein the quality control station location provides for viewing the cap following cell capture,

wherein the computer is configured to generate an image of the cap with the digital image acquisition system, and further exposing the cap to the infrared capture laser or the ultraviolet cutting laser for ablation of portions of a collected sample residing on the transfer film carrier and/or cap in the quality control station.

2. The digital microscope of claim 1 , wherein the digital microscope further includes an illumination system.

3. The digital microscope of claim 2 , wherein the illumination system comprises a white light illuminator and a condenser mounted on the frame.

4. The digital microscope of claim 1 , wherein the digital microscope further includes a handling system.

5. The digital microscope of claim 4 , wherein the handling system comprises a lift fork.

6. The digital microscope of claim 5 , wherein the lift fork is adapted to pick and move a transfer film carrier and/or cap into and out of juxtaposition with the sample-bearing substrate.

7. The digital microscope of claim 4 , wherein the handling system includes a visualization filter.

8. The digital microscope of claim 7 , wherein the visualization filter comprises diffuser glass.

9. The digital microscope of claim 1 , wherein the digital microscope further includes an optical system.

10. The digital microscope of claim 9 , wherein the optical system includes elements mounted on the frame in combination to create an optical train of optical elements for pathing light, wherein the optical system comprises one or more optical elements selected from a mirror, a dichroic mirror, a lens, an objective, a beam-diameter adjuster, a cut-off filter, a diffuser, a condenser, an eyepiece and an image acquisition system.

11. The digital microscope of claim 1 , wherein the digital microscope further includes an illumination system and an optical system.

12. The digital microscope of claim 11 , wherein the illumination system, worksurface and optical system are arranged in an inverted transmitted-light microscope fashion such that the illumination system is arranged above the worksurface and at least one objective is arranged below the worksurface.

13. The digital microscope of claim 1 , wherein the worksurface is mounted on the frame and operates as a translation stage that is automatically or manually moveable.

14. The digital microscope of claim 13 , wherein the worksurface is moveable in directions including at least the planar X-Y directions.

15. The digital microscope of claim 1 , wherein the worksurface includes slide locations for handling multiple tissue samples simultaneously and wherein each slide location includes at least one opening in the worksurface.

16. The digital microscope of claim 1 , wherein the worksurface further includes an unload station for unloading the transfer film carriers and/or caps.

Assignments (5)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 8, 2023
From: BAER, THOMAS M.; YOUNGQUIST, MICHAEL G.; DONOVAN, BRIAN W.; WESSEL, ALAN E.; LECLERC, NORBERT H.; SMITH, MICHAEL A.; DAWSON, GEORGE M.; BARKER, CRAIG S.
To: ARCTURUS BIOSCIENCE, INC.
Reel/Frame 064844/0605 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 8, 2023
From: ARCTURUS BIOSCIENCE, INC.
To: MOLECULAR DEVICES CORPORATION
Reel/Frame 064845/0076 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 8, 2023
From: MOLECULAR DEVICES, INC.
To: LIFE TECHNOLOGIES CORPORATION
Reel/Frame 064846/0071 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 8, 2023
From: MDS ANALYTICAL TECHNOLOGIES (US) INC.
To: MOLECULAR DEVICES, INC.
Reel/Frame 064852/0296 →
CHANGE OF NAME Recorded Sep 8, 2023
From: MOLECULAR DEVICES CORPORATION
To: MDS ANALYTICAL TECHNOLOGIES (US) INC.
Reel/Frame 065023/0259 →
Continuity (9)
Continuation 17516605 · Nov 1, 2021
Continuation 16790595 · Feb 13, 2020
Division 16208557 · Dec 3, 2018
Division 15434200 · Feb 16, 2017
Division 14275812 · May 12, 2014
Division 11236045 · Sep 26, 2005
Provisional Application 60664438 · Mar 23, 2005
Provisional Application 60613038 · Sep 25, 2004
Related Publication 20230400391A1 · Dec 14, 2023
References Cited (297)
US 3680947A · Wanesky · 1972 [cited by applicant]
US 3705769A · Johannsmeier · 1972 [cited by applicant]
US 3848962A · Nelson · 1974 [cited by applicant]
US 4210384A · Keydell et al. · 1980 [cited by applicant]
US 4303866A · Porro et al. · 1981 [cited by applicant]
US 4333983A · Allen · 1982 [cited by applicant]
US 4436385A · Fischer et al. · 1984 [cited by applicant]
US 4508435A · Graham et al. · 1985 [cited by applicant]
US 4509834A · Hodgson · 1985 [cited by applicant]
US 4538885A · Graham et al. · 1985 [cited by applicant]
US 4552033A · Maerzhaeuser · 1985 [cited by applicant]
US 4600282A · Yamamura et al. · 1986 [cited by applicant]
US 4614431A · Komeyama · 1986 [cited by applicant]
US 4623839A · Garretson et al. · 1986 [cited by applicant]
US 4627009A · Holmes et al. · 1986 [cited by applicant]
US 4661692A · Kawasaki · 1987 [cited by applicant]
US 4672559A · Jansson et al. · 1987 [cited by applicant]
US 4673261A · Hunt et al. · 1987 [cited by applicant]
US 4684781A · Frish et al. · 1987 [cited by applicant]
US 4702565A · Schilling et al. · 1987 [cited by applicant]
US 4731530A · Mikan · 1988 [cited by applicant]
US 4760385A · Jansson et al. · 1988 [cited by applicant]
US 4807984A · Kurimura et al. · 1989 [cited by applicant]
US 4824229A · Narita et al. · 1989 [cited by applicant]
US 4836667A · Ozeki · 1989 [cited by applicant]
US 4852985A · Fujihara et al. · 1989 [cited by applicant]
US 4856873A · Kleinberg · 1989 [cited by applicant]
US 4871245A · Ishikawa et al. · 1989 [cited by applicant]
US 4920053A · Inoue et al. · 1990 [cited by applicant]
US 4923294A · Courtenay · 1990 [cited by applicant]
US 4954715A · Zoeld · 1990 [cited by applicant]
US 4964708A · Mason · 1990 [cited by applicant]
US 4987006A · Williams et al. · 1991 [cited by applicant]
US 4992660A · Kobayashi · 1991 [cited by applicant]
US 5017428A · Mecke et al. · 1991 [cited by applicant]
US 5029791A · Ceccon et al. · 1991 [cited by applicant]
US 5037207A · Tomei et al. · 1991 [cited by applicant]
US 5057689A · Nomura et al. · 1991 [cited by applicant]
US 5077620A · Mauro · 1991 [cited by applicant]
US 5089909A · Kleinberg · 1992 [cited by applicant]
US 5103338A · Crowley et al. · 1992 [cited by applicant]
US 5126877A · Biber · 1992 [cited by applicant]
US 5143552A · Moriyama · 1992 [cited by applicant]
US 5162941A · Favro et al. · 1992 [cited by applicant]
US 5165297A · Krueger · 1992 [cited by applicant]
US 5173802A · Heller · 1992 [cited by applicant]
US 5173803A · Heller · 1992 [cited by applicant]
US 5225326A · Bresser et al. · 1993 [cited by applicant]
US 5253110A · Ichihara et al. · 1993 [cited by applicant]
US 5257182A · Luck et al. · 1993 [cited by applicant]
US 5262891A · Nakasato · 1993 [cited by applicant]
US 5263384A · Suzuki · 1993 [cited by applicant]
US 5270527A · Salzmann · 1993 [cited by applicant]
US 5280384A · Shibasaki · 1994 [cited by applicant]
US 5287272A · Rutenberg et al. · 1994 [cited by applicant]
US 5288996A · Betzig et al. · 1994 [cited by applicant]
US 5296963A · Murakami et al. · 1994 [cited by applicant]
US 5298963A · Moriya et al. · 1994 [cited by applicant]
US 5312393A · Mastel · 1994 [cited by applicant]
US 5323009A · Harris · 1994 [cited by applicant]
US 5337178A · Kung et al. · 1994 [cited by applicant]
US 5345333A · Greenberg · 1994 [cited by applicant]
US 5357366A · Marchlenski · 1994 [cited by applicant]
US 5359417A · Mueller et al. · 1994 [cited by applicant]
US 5367401A · Saulietis · 1994 [cited by applicant]
US 5378675A · Takeyama et al. · 1995 [cited by applicant]
US 5386112A · Dixon · 1995 [cited by applicant]
US 5393647A · Neukermans et al. · 1995 [cited by applicant]
US 5403735A · Maruhashi et al. · 1995 [cited by applicant]
US 5403970A · Aoki · 1995 [cited by applicant]
US 5412503A · Nederlof · 1995 [cited by applicant]
US 5420716A · Fukaya · 1995 [cited by applicant]
US 5428690A · Bacus et al. · 1995 [cited by applicant]
US 5434703A · Morizumi · 1995 [cited by applicant]
US 5450233A · Yamamoto et al. · 1995 [cited by applicant]
US 5455420A · Ho et al. · 1995 [cited by applicant]
US 5465375A · Thepaut et al. · 1995 [cited by applicant]
US 5468967A · Chan et al. · 1995 [cited by applicant]
US 5471260A · Luce et al. · 1995 [cited by applicant]
US 5479252A · Worster et al. · 1995 [cited by applicant]
US 5487117A · Burges et al. · 1996 [cited by applicant]
US 5492861A · Opower · 1996 [cited by applicant]
US 5497430A · Sadovnik et al. · 1996 [cited by applicant]
US 5504366A · Weiss et al. · 1996 [cited by applicant]
US 5506725A · Koike et al. · 1996 [cited by applicant]
US 5510615A · Ho et al. · 1996 [cited by applicant]
US 5517353A · Ikoh et al. · 1996 [cited by applicant]
US 5532128A · Eggers et al. · 1996 [cited by applicant]
US 5532476A · Mikan · 1996 [cited by applicant]
US 5532873A · Dixon · 1996 [cited by applicant]
US 5535052A · Joergens · 1996 [cited by applicant]
US 5536941A · Swann · 1996 [cited by applicant]
US 5537863A · Fujiu et al. · 1996 [cited by applicant]
US 5552928A · Furuhashi et al. · 1996 [cited by applicant]
US 5556790A · Pettit · 1996 [cited by applicant]
US 5557456A · Garner et al. · 1996 [cited by applicant]
US 5558329A · Liu · 1996 [cited by applicant]
US 5559329A · Joseph et al. · 1996 [cited by applicant]
US 5578832A · Trulson et al. · 1996 [cited by applicant]
US 5587748A · Luce et al. · 1996 [cited by applicant]
US 5587833A · Kamentsky · 1996 [cited by applicant]
US 5598888A · Sullivan et al. · 1997 [cited by applicant]
US 5602674A · Weissman et al. · 1997 [cited by applicant]
US 5619035A · Weiss et al. · 1997 [cited by applicant]
US 5621207A · O'Mara · 1997 [cited by applicant]
US 5625705A · Recht · 1997 [cited by applicant]
US 5631734A · Stern et al. · 1997 [cited by applicant]
US 5638206A · Sumiya et al. · 1997 [cited by applicant]
US 5659421A · Rahmel et al. · 1997 [cited by applicant]
US 5707801A · Bresser et al. · 1998 [cited by applicant]
US 5713803A · Oshima · 1998 [cited by applicant]
US 5715327A · Wilhelm et al. · 1998 [cited by applicant]
US 5728527A · Singer et al. · 1998 [cited by applicant]
US 5734735A · Coleman, Jr. · 1998 [cited by applicant]
US 5740269A · Oh et al. · 1998 [cited by applicant]
US 5740270A · Rutenberg et al. · 1998 [cited by applicant]
US 5745601A · Lee et al. · 1998 [cited by applicant]
US 5751839A · Drocourt et al. · 1998 [cited by applicant]
US 5767923A · Coleman, Jr. · 1998 [cited by applicant]
US 5774357A · Hoffberg et al. · 1998 [cited by applicant]
US 5778108A · Coleman, Jr. · 1998 [cited by applicant]
US 5787188A · Nelson et al. · 1998 [cited by applicant]
US 5843644A · Liotta et al. · 1998 [cited by applicant]
US 5843657A · Liotta et al. · 1998 [cited by applicant]
US 5859699A · Baer et al. · 1999 [cited by applicant]
US 5867610A · Lee · 1999 [cited by applicant]
US 5867699A · Kuslak et al. · 1999 [cited by applicant]
US 5870493A · Vogl et al. · 1999 [cited by applicant]
US 5875108A · Hoffberg et al. · 1999 [cited by applicant]
US 5889880A · Doerrer et al. · 1999 [cited by applicant]
US 5920360A · Coleman, Jr. · 1999 [cited by applicant]
US 5920477A · Hoffberg et al. · 1999 [cited by applicant]
US 5939278A · Boon et al. · 1999 [cited by applicant]
US 5959697A · Coleman, Jr. · 1999 [cited by applicant]
US 5978497A · Lee et al. · 1999 [cited by applicant]
US 5985085A · Baer et al. · 1999 [cited by applicant]
US 5987158A · Meyer et al. · 1999 [cited by applicant]
US 5998129A · Schuetze et al. · 1999 [cited by applicant]
US 5999634A · Abbott et al. · 1999 [cited by applicant]
US 6010888A · Liotta et al. · 2000 [cited by applicant]
US 6031232A · Cohenford et al. · 2000 [cited by applicant]
US 6040139A · Bova · 2000 [cited by applicant]
US 6058322A · Nishikawa et al. · 2000 [cited by applicant]
US 6061471A · Coleman, Jr. · 2000 [cited by applicant]
US 6100051A · Goldstein et al. · 2000 [cited by applicant]
US 6133943A · Needham · 2000 [cited by applicant]
US 6134354A · Lee et al. · 2000 [cited by applicant]
US 6143535A · Palsson · 2000 [cited by applicant]
US 6146897A · Cohenford et al. · 2000 [cited by applicant]
US 6148099A · Lee et al. · 2000 [cited by applicant]
US 6157446A · Baer et al. · 2000 [cited by applicant]
US 6181811B1 · Kuan et al. · 2001 [cited by applicant]
US 6184973B1 · Baer et al. · 2001 [cited by applicant]
US 6204030B1 · Liotta et al. · 2001 [cited by applicant]
US 6215550B1 · Baer et al. · 2001 [cited by applicant]
US 6215892B1 · Douglass et al. · 2001 [cited by applicant]
US 6226392B1 · Bacus et al. · 2001 [cited by applicant]
US 6229568B1 · Kawaguchi et al. · 2001 [cited by applicant]
US 6240209B1 · Wilcke · 2001 [cited by applicant]
US 6251516B1 · Bonner et al. · 2001 [cited by applicant]
US 6259807B1 · Ravkin · 2001 [cited by applicant]
US 6316234B1 · Bova · 2001 [cited by applicant]
US 6327377B1 · Rutenberg et al. · 2001 [cited by applicant]
US 6335980B1 · Armato, III et al. · 2002 [cited by applicant]
US 6337926B2 · Takahashi et al. · 2002 [cited by applicant]
US 6420132B1 · Bonner et al. · 2002 [cited by applicant]
US 6456899B1 · Gleason et al. · 2002 [cited by applicant]
US 6469779B2 · Baer et al. · 2002 [cited by applicant]
US 6495195B2 · Baer et al. · 2002 [cited by applicant]
US 6512576B1 · Baer et al. · 2003 [cited by applicant]
US 6528248B2 · Lossing et al. · 2003 [cited by applicant]
US 6531318B1 · Palmer-Toy et al. · 2003 [cited by applicant]
US 6569639B2 · Liotta et al. · 2003 [cited by applicant]
US 6639657B2 · Baer et al. · 2003 [cited by applicant]
US 6690470B1 · Baer et al. · 2004 [cited by applicant]
US 6697149B2 · Baer et al. · 2004 [cited by applicant]
US 6750964B2 · Levenson et al. · 2004 [cited by applicant]
US 6757412B1 · Parsons et al. · 2004 [cited by applicant]
US 6790636B1 · Star · 2004 [cited by examiner]
US 6858007B1 · Akselrod et al. · 2005 [cited by applicant]
US 6867038B2 · Liotta et al. · 2005 [cited by applicant]
US 7027133B2 · Baer et al. · 2006 [cited by applicant]
US 7075640B2 · Baer et al. · 2006 [cited by applicant]
US 7221447B2 · Baer et al. · 2007 [cited by applicant]
US 7456938B2 · Malekafzali · 2008 [cited by applicant]
US 8346483B2 · Kil · 2013 [cited by applicant]
US 8715955B2 · Donovan et al. · 2014 [cited by applicant]
US 8722357B2 · Baer et al. · 2014 [cited by applicant]
US 10156501B2 · Baer et al. · 2018 [cited by applicant]
US 20010003009A1 · Baer et al. · 2001 [cited by applicant]
US 20010005586A1 · Palsson et al. · 2001 [cited by applicant]
US 20010028934A1 · Baer et al. · 2001 [cited by applicant]
US 20020001837A1 · Baer et al. · 2002 [cited by applicant]
US 20020015949A1 · Erlander et al. · 2002 [cited by applicant]
US 20020090122A1 · Baer et al. · 2002 [cited by applicant]
US 20020103512A1 · Echauz et al. · 2002 [cited by applicant]
US 20020142412A1 · Ogawa et al. · 2002 [cited by applicant]
US 20020177885A1 · Eisfeld et al. · 2002 [cited by applicant]
US 20030030801A1 · Levenson et al. · 2003 [cited by applicant]
US 20030032082A1 · Leclerc · 2003 [cited by applicant]
US 20030058430A1 · Baer et al. · 2003 [cited by applicant]
US 20030207265A1 · Church · 2003 [cited by applicant]
US 20030219151A1 · Curry et al. · 2003 [cited by applicant]
US 20040051880A1 · Seko et al. · 2004 [cited by applicant]
US 20040052328A1 · Sabol et al. · 2004 [cited by applicant]
US 20040063326A1 · Szlufcik et al. · 2004 [cited by applicant]
US 20040076613A1 · Mazarakis et al. · 2004 [cited by applicant]
US 20040080818A1 · Olschewski · 2004 [cited by applicant]
US 20040093166A1 · Kil · 2004 [cited by applicant]
US 20040252291A1 · Schutze · 2004 [cited by applicant]
US 20050089949A1 · Baer et al. · 2005 [cited by applicant]
US 20060087643A1 · Donovan · 2006 [cited by examiner]
US 20060134692A1 · Emmert-Buck et al. · 2006 [cited by applicant]
US 20060172278A1 · Bonner et al. · 2006 [cited by applicant]
US 20070066967A1 · Sieckmann et al. · 2007 [cited by applicant]
US 20090140169A1 · Niehren · 2009 [cited by applicant]
US 20130171617A1 · Thalhammer · 2013 [cited by examiner]
US 20140335560A1 · Baer et al. · 2014 [cited by applicant]
CH 566015A5 · 1975 [cited by applicant]
DE 1263339B · 1968 [cited by applicant]
DE 19603996A1 · 1997 [cited by applicant]
DE 19636074A1 · 1998 [cited by applicant]
EP 0611598A2 · 1994 [cited by applicant]
EP 0748439B1 · 1999 [cited by applicant]
EP 1186878A2 · 2002 [cited by applicant]
WO WO1991007683A1 · 1991 [cited by applicant]
WO WO199319207A1 · 1993 [cited by applicant]
WO WO1994002646A1 · 1994 [cited by applicant]
WO WO1995023960A1 · 1995 [cited by applicant]
WO WO1995030919A1 · 1995 [cited by applicant]
WO WO1997013838A1 · 1997 [cited by applicant]
WO WO1998027543A2 · 1998 [cited by applicant]
WO WO1998035216A1 · 1998 [cited by applicant]
WO WO1998044446A1 · 1998 [cited by applicant]
WO WO1999019341A1 · 1999 [cited by applicant]
WO WO1999045094A1 · 1999 [cited by applicant]
WO WO2000034756A2 · 2000 [cited by applicant]
WO WO2000034757A1 · 2000 [cited by applicant]
WO WO2001033190A2 · 2001 [cited by applicant]
WO WO2002037159A2 · 2002 [cited by applicant]
WO WO2002057746A2 · 2002 [cited by applicant]
WO WO2004025569A2 · 2004 [cited by applicant]
Allred, et al., “Biological features of human premalignant breast disease,” Chapter 24 in Disease of the Breast, 2nd ed., Jay R. Harris, ed., Lippicott Williams & Wilkins: Philadelphia, pp. 355-366. [cited by applicant]
Anonymous, “ChromaVision” website product description including Rare Cell Detection in Tissue and Rare Cell Detection in Cytospin Prep—retrieval date Jun. 21, 2004. [cited by applicant]
Ashkin, et al., “Internal cell manipulation using infrared laser traps”, Proceedings of the National Academy of Sciences, vol. 86, No. 20, Oct. 1989, pp. 7914-7918. [cited by applicant]
Bonner, et al. “Laser capture microdissection: Molecular analysis of tissue,” Science, vol. 278, No. 5342, Nov. 21, 1997, pp. 1481-1483. [cited by applicant]
Bonner et al., “Lasers and Electro-Optics”, Summaries of Papers Presented at the Conference on May 23-28, 1999, pp. 398-399. [cited by applicant]
Darling et al., “Revertant mosaicism : partial correction of a germ-line mutation in COL17A1 by a frame-restoring mutation,” Journal of Clinical Investigation, vol. 103, No. 10, May 15, 1999, pp. 1371-1377. [cited by applicant]
Duke University, “Evaluation of Cervical Cytology,” AHCPR publication No. 99-E010, Feb. 1999. [cited by applicant]
Emmert-Buck et al. “Laser Capture Microdissection,” Science, vol. 274, No. 5289, Nov. 8, 1996, pp. 998-1001. [cited by applicant]
EP05797889.2, Extended Search Report, Mar. 21, 2012, 7 pages. [cited by applicant]
Fend, et al.,“ Immuno-LCM : Laser Capture Microdissection of Immunostained Frozen Sections for mRNA Analysis, ” American Journal of Pathology, vol. 154, No. 1, Jan. 1999, pp. 61-66. [cited by applicant]
Friend, “Getting up close to cancer genes,” USA Today, Science Section, Aug. 5, 1997, p. 4D. [cited by applicant]
Frosini, et al., “A modified fuzzy C-means algorithm for feature selection”, Peachfuzz 2000, 19th International Conference of the North American Fuzz˜ Information Processing Societv. Piscataway, NJ, USA, 2000, pp. 148-1… [cited by applicant]
Fukui, et al. “Microdissection of plant chromosomes by argon-ion laser beam,” Theoretical & Applied Genetics, vol. 84, Nos. 7-8, Sep. 1992, pp. 787-791. [cited by applicant]
Goldstein, et al. “Thermal modeling of laser capture microdissection” Applied Optics, vol. 37, No. 31, Nov. 1, 1998, pp. 7378-7391. [cited by applicant]
Grohs, “Automated Cervical Cancer Screening,” Igaku-Shoin Medical Publishers, Chapter 23, 1994, pp. 305-317. [cited by applicant]
Harlow, “Antibodies: A Laboratory Manual,” New York, Cold Spring Harbor, 1988, pp. iii-ix (Table of Contents). [cited by applicant]
Heng, et al., “High-Resolution Mapping of Mammalian Genes by In-Situ Hybridization to Free Chromatin,” Proceedings of the National Academy of Sciences, vol. 89, No. 20, Oct. 1992, pp. 9509-9513. [cited by applicant]
Isenberg, et al., “Cell surgery by laser micro-dissection: a preparative method”, Journal of Microscopy, vol. 107, No. 1, May 1976, pp. 19-24. [cited by applicant]
Jarkrans. “Algorithms for Cell Image Analysis in Cytology and Pathology,” Comprehensive Summaries of Uppsala Dissertations (1996). [cited by applicant]
Jeyendran. “Association of the in-vitro fertilizing capacity of human spermatozoa with sperm morphology as assessed by three classification systems”, Human Reproduction, vol. 1, No. 5, Aug. 1986, pp. 305-308. [cited by applicant]
Jimenez, et al., “Neuropeptide Expression and Processing as Revealed by Direct Matrix-Assisted Laser Desorption Ionization Mass Spectrometry of Single Neurons”, Journal of Neurochemistry, vol. 62, No. 1, Jan. 1994, pp. … [cited by applicant]
Jong-Min Park, et al., “Analysis of active feature selection in optic nerve data using labeled fuzzy C-means clustering”, 2002 IEEE World Congress on Computational Intelligence, 2002 IEEE International Conference on Fuz… [cited by applicant]
Koperski, et al. “Interactive models for semantic labeling of satellite images,” Proceedings of the SPIE, vol. 4814, Sep. 2002, pp. 423-434. [cited by applicant]
Kubo, et al., “Early Detection of Knudson's Two-Hits in Preneoplastic Renal Cells of the Eker Rat Model by the Laser Microdissection Procedure”, Cancer Research, vol. 55, No. 5, Mar. 1, 1995, pp. 989-990. [cited by applicant]
Kuska. “New aim-and-shoot technique speeds up cell analysis,” Journal of the National Cancer Institute, vol. 88, No. 23, 1996, pp. 1708-1709. [cited by applicant]
Lawrence, et al., “Sensitive, high-resolution chromatin and chromosome mapping in situ: Presence and orientation of two closely integrated copies of EBV in a lymphoma line,” Cell, vol. 52, No. 1, Jan. 15, 1988, pp. 51-6… [cited by applicant]
LCM, Introduction to Laser Capture Microdissection, http://dir.nichd.nih.gov/lcm/LCMWebsite Introduction.htm, 1996-1997, pp. 1-3. [cited by applicant]
LCM R&D Lab, http://dir.nichd.nih.gov/lcm/Text_for_RD_Core1.htmi#Computer%20control, 1997, pp. 1-2 and 1-4. [cited by applicant]
Lewis, “Laser aids Alzheimer's study,” Bioghotonics International, Nov./Dec. 1998, 2 pages. [cited by applicant]
Lichter, et al., “High-Resolution Mapping of Human Chromosome 11 by In-Situ Hybridization with Cosmid Clones,” Science, vol. 247, No. 4938, Jan. 5, 1990, pp. 64-69. [cited by applicant]
Manuelidis, et al., “High-Resolution Mapping of Satellite DNA Using Biotin-Labeled DNA Probes,” Journal of Cell Biology, vol. 95, No. 2, Nov. 1982, pp. 619-625. [cited by applicant]
Meier-Ruge et al. “The laser in the Lowry technique for microdissection of freeze-dried tissue slices,” Histochemical Journal, vol. 8, No. 5, Jul. 1976, pp. 387-401. [cited by applicant]
Morruzzi, et al., “Quantification and classification of human sperm morphology by computer assisted image analysis”, Fertility Sterility, vol. 50, No. 1, Jul. 1988, pp. 142-152. [cited by applicant]
PCT/US2000/041946, Search Report, Nov. 9, 2001, 5 pages. [cited by applicant]
PCT/US2000/41899, Search Report, Jan. 7, 2002, 5 pages. [cited by applicant]
PCT/US2001/047298, Search Report, Jul. 2, 2002, 3 pages. [cited by applicant]
PCT/US2003/029060, Search Report, Oct. 27, 2004, 5 pages. [cited by applicant]
PCT/US2005/31897, Search Report, Jun. 13, 2008, 2 pages. [cited by applicant]
Perez-Sanchez. “Morphometric Analysis of human sperm morphology” International Journal of Andrology, vol. 17, No. 5, Oct. 1994, pp. 248-255. [cited by applicant]
Petrosian, et al., “Computer-Aided Diagnosis in Mammography: Classification of Mass and Normal Tissue by Texture Analysis,” Physics in Medicine & Biology, vol. 39, No. 12, 1994, pp. 2273-2288. [cited by applicant]
Pizzi, “Diagnostic Cytology Learning Page” http://www-ocs.colorado.edu/-metzj/pizzia/learning.sub.--page.html Written Feb. 4, 1997, Last updated Aug. 4, 1998. [cited by applicant]
Rangayyan, et al., “Measures of Acutance and Shape for Classification of Breast Tumors”, IEEE Transactions on Medical Imaging, vol. 16, No. 6, Dec. 1997, pp. 799-810. [cited by applicant]
Sahiner, et al., “Improvement of Mammographic Mass Characterization Using Spiculation Measures and Morphological Features”, Medical Physics, vol. 28, No. 7, Jul. 2001, pp. 1455-1465. [cited by applicant]
Salomie, et al., “Multivariate Techniques for Medical Image Segmentation”, http://www.etro.vub.ac.be/members/deklerck.rudi/redimedia/segmentation/se--gment.htm , 2001. [cited by applicant]
Salomie, et al., “Multivariate Techniques for Medical Image Segmentation,” http://www.etro.vub.ac.be/members/deklerck.rudi/redimedia/segmentation/se-gment.htm, Jun. 28, 1999. [cited by applicant]
Schachter, et al., “Some Experiments in Image Segmentation by Clustering of Local Feature Values”, Pattern Recognition, vol. 11, No. 1, 1979, pp. 19-28. [cited by applicant]
Schindler, “Select, microdissect, and eject”, Nature Biotechnology, vol. 16, No. 8, Aug. 1998, pp. 719-720. [cited by applicant]
Schindler, et al., “Automated Analysis & Survival Selection of Anchorage-Dependent Cells Under Normal Growth Conditions,” Cytometry, vol. 6, No. 4, 1985, pp. 368-374. [cited by applicant]
Schutze, et al., “Identification of expressed genes by laser-mediated manipulation of single cells”, Nature Biotechnology, vol. 16, No. 8, Aug. 1998, pp. 737-742. [cited by applicant]
Simone, et al.: “Laser-capture microdissection: opening the microscopic frontier to molecular analysis”, Trends in Genetics, vol. 14, No. 7, Jul. 1, 1998, pp. 272-276. [cited by applicant]
Srinivasan, “Ablation of polymers and biological tissue by ultraviolet lasers,” Science, vol. 234, 1986, pp. 559-565. [cited by applicant]
Suarez-Quian, et al., “Laser Capture Microdissection of Single Cells from Complex Tissues”, Bio-Techiques, vol. 26, No. 2, 1999, pp. 328-335. [cited by applicant]
UCSD Cancer Center, http://cancer.ucsd.edu/molpath/examples.asp . And also see http://cancer.ucsd.edu/molpath/introduce.asp (retrieved from U.S. Appl. No. 10/011,515 892 Mar. 10, 2004). [cited by applicant]
Van Den Engh, et al., “Estimating Genomic Distance from DNA Sequence Location in Cell Nuclei by a Random Walk Model”, Science, vol. 257, Sep. 1992, pp. 1410-1412. [cited by applicant]
Veigel, et al., “New cell biological applications of a laser microbeam technique: the microdissection and skinning of muscle fibers and the perforation and fusion of sarcolemma vesicles”, European Journal of Cell Biolog… [cited by applicant]