AU2006292394A1 - Systems and methods for enrichment of analytes - Google Patents

Systems and methods for enrichment of analytes Download PDF

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Publication number
AU2006292394A1
AU2006292394A1 AU2006292394A AU2006292394A AU2006292394A1 AU 2006292394 A1 AU2006292394 A1 AU 2006292394A1 AU 2006292394 A AU2006292394 A AU 2006292394A AU 2006292394 A AU2006292394 A AU 2006292394A AU 2006292394 A1 AU2006292394 A1 AU 2006292394A1
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Australia
Prior art keywords
analyte
cell
sample
cells
chromosome
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AU2006292394A
Inventor
Ulysses Balis
Tom Barber
Bruce Carvalho
Darren Gray
Michael Grisham
Lotien Richard Huang
Ravi Kapur
Martin Schmidt
Ron Tompkins
Mehmet Toner
John Walsh
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General Hospital Corp
Artemis Health Inc
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General Hospital Corp
Artemis Health Inc
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Publication date
Priority claimed from US11/229,328 external-priority patent/US20070059718A1/en
Priority claimed from US11/229,037 external-priority patent/US20070059774A1/en
Priority claimed from US11/228,454 external-priority patent/US20070059716A1/en
Priority claimed from US11/228,462 external-priority patent/US20070059680A1/en
Priority claimed from US11/229,332 external-priority patent/US20070059719A1/en
Priority claimed from US11/229,336 external-priority patent/US20070059781A1/en
Application filed by General Hospital Corp, Artemis Health Inc filed Critical General Hospital Corp
Publication of AU2006292394A1 publication Critical patent/AU2006292394A1/en
Abandoned legal-status Critical Current

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    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/80—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood groups or blood types or red blood cells
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B20/00—ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
    • G16B20/20—Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
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    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502761—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules
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    • G01—MEASURING; TESTING
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    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
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    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
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    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
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    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
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    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
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    • B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
    • B01L2200/0668—Trapping microscopic beads
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    • B01L2400/08—Regulating or influencing the flow resistance
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    • B01L2400/086—Passive control of flow resistance using baffles or other fixed flow obstructions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C2201/00—Details of magnetic or electrostatic separation
    • B03C2201/18—Magnetic separation whereby the particles are suspended in a liquid
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C2201/00—Details of magnetic or electrostatic separation
    • B03C2201/26—Details of magnetic or electrostatic separation for use in medical applications
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y15/00—Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
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    • B82—NANOTECHNOLOGY
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    • B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
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    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G01N1/4077—Concentrating samples by other techniques involving separation of suspended solids
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    • G01N2800/00—Detection or diagnosis of diseases
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    • G01N2800/387—Down syndrome; Trisomy 18; Trisomy 13
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Description

INTERNATIONAL SEARCH REPORT International application No. PCT/US 06/36202 A. CLASSIFICATION OF SUBJECT MATTER IPC(8) - C12Q 1/68 (2007.01) USPC - 435/6 According to International Patent Classification (IPC) or to both national classification and IPC B. FIELDS SEARCHED Minimum documentation searched (classification system followed by classification symbols) USPC 435/6 Documentation searched other than minimum documentation to the extent that such documents are included in the fields searched USPC all subclasses of 435 - see keywords below Electronic data base consulted during the international search (name of data base and, where practicable, search terms used) PubWest (USPT, PGPB, EPAB, JPAB), DialogPRO (Patents), MedLine, PubMed, Google Patents, Google Scholar Search Terms Used: fetal hemoglobin, globin, selectins, computer, size-based separation, cell separation, two dimensional array, and combinations thereof. C. DOCUMENTS CONSIDERED TO BE RELEVANT Category* Citation of document, with indication, where appropriate, of the relevant passages Relevant to claim No. X WO 2004/0029221 A2 (TONER et al.) 08 April 2004 (08.04.2004) Entirety. Esp. pg. 3, In 15-26; 30 Claim 1-3; pg. 18, In 10-11; pg. 4, In 13-14; pg. 4, In 24-26; pg. 3, In 25-26; pg. 5, In 13-17; pg. ---- Y 19, In 1-11; Claim 27; pg 3, In 7-10; pg. 35, In 26 - pg. 36, In 2; pg. 4, In 10-19; pg. 8, In 7-9; 1-29, 31-38, 55-68, 81-99 Figure 20A; pg. 33, In 19-20; pg. 27, In 24-28; pg. 31, In 22-28; Claim 61 Y US 2004/0048360 Al (WADA et al.) 11 March 2004 (11.03.2004) Entirety. Esp. Claims 3, 4, 22; 1-29, 31-38, 55-68, 81-99 [0029]; [0142]-0047]; [0139]; [0011]; [0132]; [0012]; [0134]; [0133]; [0014]; [0103]; Claim 9; [0107]; Claim 11; Claim 13; [0096] SFurther documents are listed in the continuation of Box C. ] * Special categories of cited documents: "T' later document published after the international filing date orpriority "A" document defining the general state of the art which is not considered date and not in conflict with the application but cited to understand to be of particular relevance the principle or theory underlying the invention "E" earlier application or patent but published on or after the international "X" document of particular relevance; the claimed invention cannot he filing date considered novel or cannot be considered to involve an inventive "L" document which may throw doubts on priority claim(s) or which is step when the document is taken alone cited to establish the publication date of another citation or other "Y" document of particular relevance; the claimed invention cannot be special reason (as specified) considered to involve an inventive step when the document is "O" document referring to an oral disclosure, use, exhibition or other combined with one or more other such documents, such combination means being obvious to a person skilled in the art "P" document published prior to the international filing date but later than "&" document member of the same patent family the priority date claimed Date of the actual completion of the international search Date of mailing of the international search report 13 June 2007 (13.06.2007) SE 7 Name and mailing address of the ISA/US Authorized officer: Mail Stop PCT, Attn: ISA/US, Commissioner for Patents Lee W. Young P.O. Box 1450, Alexandria, Virginia 22313-1450 PCT Helpdesk: 571-272-4300 Facsimile No. 571-273-3201 PCTOSP: 571-272-7774 Form PCT/ISA/210 (second sheet) (April 2005)

Claims (83)

1. A system comprising: 5 one or more size-based separation modules adapted to increase a concentration of a first analyte in a sample by at least 10,000 fold, wherein said first analyte has an initial concentration in said sample of less than 1 x 10 -3 analytes/pL, and an analyzer comprising computer executable logic for analyzing said first analytes in an enriched medium. 10 2. The system of claim 1 wherein said analyzer further comprises a microscope, a microarray, or cell counter.
3. The system of claim 1 wherein said computer executable logic detects a color change in the presence of fetal hemoglobin, globin , globin e, globin 3, GPA, i-antigen, CD36, selectins, CD71 or-a combination thereof. 15 4. The system of claim 1 wherein said computer executable logic detects intensities of probes that selectively bind said first analytes.
5. The system of claim 1 wherein said computer executable logic performs three-dimensional image analysis of said first analytes.
6. The system of claim 1 wherein said analyzer has dual scanning capabilities. 20 7. The system of claim 1 wherein said computer executable logic images said first analytes.
8. The system of claim 1 wherein said computer executable logic determines trisomy, sex of a fetus, genetic or chromosomal abnormalities in a cell of interest, or a combination thereof.
9. The system of claim 1 wherein each of said size-based separation modules comprises a two dimensional array of obstacles that direct said first analyte deterministically in a first direction and a second analyte 25 having a hydrodynamic size smaller than said first analyte in a second direction.
10. The system of claim 9 wherein said first analyte is a nucleated red blood cell.
11. The system of claim 9 wherein said first analyte is a fetal nucleated red blood cell.
12. The system of claim 1 wherein said system comprises two or more size-based separation modules fluidly coupled in parallel with one another. 30 13. The system of claim 1 adapted for high-throughput analysis of at least 10 mL of said fluid sample per hour.
14. The system of claim 1 further comprising one or more capture modules fluidly coupled to said size-based separation modules, wherein said capture modules selectively capture said first analyte or a second analyte from said sample. 35 15. The system of claim 14 wherein each of said capture modules comprises a two-dimensional array of obstacles.
16. The system of claim 14 wherein each of said capture modules comprises a two-dimensional array of obstacles coupled to one or more antibodies.
17. The system of claim 16 wherein said antibodies selectively bind a red blood cell, a white blood 40 cell, a fetal blood cell, a fetal nucleated blood cell, a cancer cell, an epithelial cell, or stem cell, a progenitor cell, a foam cell, or a platelet. -40- WO 2007/035585 PCT/US2006/036202 "f' / s ' LJ i r: i i[i[ ha obmd i illii. i 16 wherein said antibodies are selected from the group consisting of: anti CD71, anti-CD36, anti-CD451, anti-GPA, anti-selectin, anti-carbohydrates, anti-antigen-i, and anti-EpCaM.
19. The system of claim 1 wherein said fluid sample is a blood sample and said first analyte is selected from the group consisting of: an epithelial cell, an endothelial cell, a progenitor cell, a stem cell, a foam 5 cell, or a cancer cell.
20. The system of claim 1 wherein said fluid sample is a blood sample and is less than 5 mL.
21. The system of claim 1 wherein said fluid sample is a blood sample derived from a female who is in less than 12 weeks of gestation.
22. The system of claim 1 wherein gap between obstacles in said separation regions is less than 1000 10 microns.
23. The system of claim 1 further comprising a reservoir containing magnetic particles fluidly coupled to said separation region or said capture regions.
24. The system of claim 1 wherein said system further comprises magnetic beads adapted to preferentially bind to said first analyte or said second analyte. 15 25. The system of claim 24 wherein said magnetic beads are coupled to an antibody that specifically binds said first analyte.
26. The system of claim 1 further comprising a reservoir fluidly coupled to said size-based separation module, wherein said reservoir contains magnetic particles adapted to preferentially bind said first analyte.
27. The system of claim 2 wherein said analyzer comprises a microarray adapted to detect one or more 20 SNPs in said first analyte.
28. The system of claim 2 wherein said analyzer comprises a microarray adapted to detect levels of mRNA in said first analyte.
29. The system of claim 9 wherein said obstacles are separated by gaps which direct the flow of sample unequally into subsequent gaps. 25 30. A system comprising a separation module adapted for removal of more than 99.5% of enucleated cells from a blood sample and retention of more than 99% of nucleated cells from a blood sample.
31. The system of claim 31 further comprising an analyzer fluidly coupled to said separation module adapted to analyze one or more of said nucleated cells and a database for storing analysis data.
32. A system comprising: 30 one or more first enrichment regions, wherein said enrichment regions comprise a two dimensional plurality of obstacles defining a first fluid flow path for a first analyte and a second fluid flow path for a second analyte wherein said first analyte and said second analyte have different hydrodynamic diameters; an analyzer fluidly coupled to said one or more enrichment regions for obtaining data on said first analyte or said second analyte; and 35 a database for storing said data.
33. The system of claim 32 wherein said first analyte is selected from the group consisting of a red blood cell (RBC), a nucleated red blood cell (NRBC), a fetal RBC, a fetal nucleated RBC (fNRBC), a trophoblast, a fetal fibroblast, a white blood cell (WBCs), an infected WVBC, a stem cell, an epithelial cell, an endothelial cell, a stem cell, a cancer cell, a viral cell, a bacterial cell, and protozoan. 40 34. The system of claim 32 wherein said cell type is found in vivo at a concentration of less than 1 x 10 -3 cells/pL. -41- WO 2007/035585 PCT/US2006/036202 Pil: "r/ 039,i I'l IEiih a llh D n 32 wherein gaps between obstacles in said first enrichment region is at most 1000 microns.
36. The system of claim 32 further comprising one or more second enrichment regions comprising, wherein said second enrichment regions captures said first analyte or said second analyte, and wherein said second 5 enrichment region is in fluid communication with said first enrichment region.
37. The system of claim 32 wherein said one or more first enrichment-regions are adapted to retain at least 99% of said first analyte.
38. The system of claim 32 wherein said one or more first enrichment regions are adapted to increase concentration of said first analyte by at least a factor of 100,000. 0 39. A method for identifying a characteristic associated with a condition in a patient comprising: obtaining a plurality of control samples; obtaining a plurality of case samples; applying each of said samples to a device comprising a plurality of obstacles that deflect a first analyte from said sample in a direction away from a second analyte of said blood sample wherein said first analyte 5 and said second analyte have a different hydrodynamic diameter; analyzing said first analyte from said samples to determine a characteristic of said first analyte; and performing an association study based on said characteristic.
40. The method of claim 39 wherein said characteristic is the presence or absence of said first analyte. 0 41. The method of claim 39 wherein said characteristic is the number of said first analyte.
42. -The method of claim 39 wherein said characteristic is a morphology or phenotype of said first analyte.
43. The method of claim 39 wherein said characteristic is the genotype of said first analyte.
44. The method of claim 39 wherein said characteristic is the proteome of said first analyte. :5 45. . The method of claim 39 wherein said characteristic is the RNA composition of said first analyte.
46. The method of claim 39 wherein said characteristic is the level of gene expression of said first analyte.
47. The method of claim 39 wherein said plurality of control samples comprises at least 100 control samples. 0 48. The method of claim 39 wherein said plurality of case samples comprises at least 100 case samples.
49. The method of claim 39 wherein said control samples and case samples are blood samples.
50. The method of claim 49 wherein each blood sample comprises less than 100 mnL of blood.
51. The method of claim 39 wherein said analyte is a cell type. 35 52. The method of claim 51 wherein said analyte is an epithelial cell, a cancer cell, or a fetal cell.
53. The system of claim 32 wherein said obstacles deterministically direct said fluid flow for said first and second analytes.
54. The system of claim 53 wherein said array of obstacles define gaps which direct the flow of sample unequally into subsequent gaps. 0 55. A method for detecting a biohazard analyte in a sample wherein said biohazard analyte is found at a concentration less than 1 x 10 - 3 analytes/pL of a sample comprising: -42- WO 2007/035585 PCT/US2006/036202 ( '1" / ILM L IC Ilippfl1~gii~ eto:a flo6v-through concentrator adapted to increase the concentration of said analyte by at least 10,000 fold, and analyzed said concentrated biohazard analyte.
56. The method of claim 55 wherein said concentrator is adapted to retain at least 99% of said 5 biohazard analyte.
57. The method of claim 55 wherein said concentrator is adapted to enrich said biohazard analyte by a factor of at least 100,000.
58. The method of claim 55 wherein said concentrator has specificity of at least 98% and sensitivity of at least 98%. 0 59. The method of claim 55 wherein said biohazard analyte is a pathogen selected from the group consisting of: a bacterium, a protozoan, a virus and a chimera thereof.
60. The method of claim 55 wherein said biohazard analyte is a pathogen selected from the group consisting of: Yersinia pestis, Bacillus anthracis, Clostridium botulinum, Francisella tularensis, Coxiella burnetii, Brucella spp., Burkholderia mallei, Burkholderia pseudomallei, Streptococcus, Ebola virus, Lassa virus, SARS, 5 Variola major, Alphaviruses, Rickettsia prowazekii, Chlamydia psittaci, Salmonella spp., Escherichia coli 0157:H7, Vibrio cholerae, Cryptosporidium parvum, Nipah virus, and hantavirus.
61. The method of claim 55 wherein said sample is a water sample, an air sample, a food sample, a bodily fluid sample, or a soil sample.
62. The method of claim 55 wherein said sample is a fluid sample. !0 63. The method of claim 55 further comprising the step of liquefying said sample to convert it to a fluid sample.
64. The method of claim 55 wherein said concentrator removes at least 99% of a second analyte from said sample.
65. The method of claim 55 wherein said biohazard analyte is a cell type. 5 66. The method of claim 55 wherein said biohazard analyte is a toxin.
67. The method of claim 55 wherein said analyzing set is preformed by a computer executable logic.
68. The method of claim 55 wherein said concentrator comprises a two dimensional array of a plurality of obstacles which deterministically direct said biohazard analyte in a first direction and a second analyte in said sample in a second direction. 30 69. A method of identifying fetal abnormality, comprising: delivering a maternal blood sample from a pregnant female to a flow through modulewhich deterministically separates fetal cells in said sample; delivering said separated fetal cells to an analyzer adapted for capturing an image of one or more fetal cell enriched from said blood sample; analyzing signals from one or more nucleic acid probes that bind fetal nucleic acids; 35 analyzing said signals; and generating a diagnostic output according based on said analyzing step.
70. The method of claim 69 wherein said probes are specific to a chromosome.
71. The method of claim 70 wherein said chromosome is selected from the group consisting of: X chromosome, Y chromosome, chromosome 21, chromosome 13 and chromosome 18. 40 72. The method of claim 70 wherein said analyzing comprises determining number of said probe signals, determining size of said probe signals, determining shape of said probe signals, determining aspect ratio of said probe signals, or determining distribution of said probe signals. -43- WO 2007/035585 PCT/US2006/036202 S l '"1P ,! :!$ 1 I!A od[ ip} product- that detects a condition of a fetus comprising: computer code that detects nucleated red blood cells in a sample; computer code that receives probe signals from one or more nucleic acid probes that bind nucleic acids of interest; 5 computer code that analyzes said probe signals to detect one or more fetal cells; computer code that analyzes said probe signals to detect a condition in said one or more fetal cells; and a computer readable medium that stores the computer codes.
74. The computer program product of claim 73 wherein the computer readable medium is a memory, 0 hard drive, floppy disk, CD-ROM, flash memory, or tape.
75. The computer program product of claim 73 wherein said probes are specific to a chromosome.
76. The computer program product of claim 75 wherein said chromosome is selected from the group consisting of: X chromosome, Y chromosome, chromosome 21, chromosome 13 and chromosome 18.
77. The computer program product of claim 73 wherein said probes are colorimetric probes. 5 78. The computer program product of claim 73 wherein said probes are fluorescent probes.
79. The method of claim 69 wherein said female is at 12 weeks or less gestation.
80. The method of claim 69 wherein said flow through module comprises one or more two dimensional arrays of obstacles wherein said obstacles define gaps which direct the sample flow unequally into subsequent gaps. 20 81. A kit for prenatal testing comprising: a size-based flow-through separation module adapted to isolate one or more cells of a first cell type from a maternal blood sample wherein said first cell type is found in vivo in a pregnant female at a concentration of less than 1% of all blood cells, and a set of instructions for analyzing said one or more enriched cells to make a prenatal diagnosis of a fetus. 25
82. A kit for prenatal testing comprising: a size-based flow-through separation module adapted to isolate one or more cells of a first cell type from a neonate blood sample wherein said first cell type is found in vivo at a concentration of less than 1% of all blood cells, and a set of instructions for analyzing said one or more enriched cells to make a prenatal diagnosis of 30 a fetus.
83. The kit of claim 81 or 82 further comprising one or more reagents selected from the group consisting of: a PCR reagent, a lysis reagent, a nucleic acid probe, and a labeling reagent.
84. The kit of claim 81 or 82 wherein said labeling reagent is a FISH reagent. 35 85. The kit of claim 81 or 82 wherein said FISH reagent specifically binds a chromosome selected from the group consisting of X chromosome, Y chromosome, chromosome 13, chromosome 18, and chromosome 21.
86. The kit of claim 81 or 82 further comprising a microarray.
87. The kit of claim 81 or 82 wherein said size-based separation module comprises a two-dimensional 40 array of obstacles that deterministically direct said one or more cells of a first cell type in a first direction and one or more cells of a second cell type in a second direction.
88. The kit of claim 87 wherein said first cell type is a fetal cell. -44- WO 2007/035585 PCT/US2006/036202 IP . I " . ,. ll t:he kildhCAl1 herei said second cell type is an enucleated red blood cell.
90. The kit of claim 89 wherein said size-based separation module retains more than 99% of said first cell types and removes more than 99% of said enucleated red blood cells.
91. The kit of claim 81 or 82 further comprising an array of obstacles, wherein said obstacles are 5 coupled to an antibody is selected from the group consisting of an anti-CD71, anti-CD36, anti-selectin, anti-GPA, anti-CD45, and anti-antigen i.
92. The kit of claim 81 or 82 wherein said prenatal diagnosis comprises determining sex of a fetus.
93. The kit of claim 81 or 82 wherein said prenatal diagnosis comprises determining the existence trisomy 13, trisomy 18, trisomy 21 (Down's Syndrome), Turner Syndrome (damaged X chromosome), Klinefelter 0 Syndrome (XXY) or another irregular number of sex or autosomal chromosomes.
94. The kit of claim 81 wherein said prenatal diagnosis comprises determining a condition selected from the group consisting of: Wolf-Hirschhomrn syndrome (4p-), Cri-du-chat (5p-), Williams syndrome (7ql 1.23), Prader-Willi syndrome (15ql 1.2-q13), Angelman syndrome (15ql 1.2-q13), Miller-Dieker syndrome (17pl3.3), Smith-Magenis syndrome (17p 11.2), DiGeorge and Velo-cardio-facial syndromes (22q11.2), Kallman syndrome 5 (Xp22.3), Steroid Sulfatase Deficiency (STS) (Xp22.3), X-Linked Ichthiosis (Xp22.3), and Retinoblastoma (13q14).
95. The kit of claim 81 or 82 wherein said separation module deterministically directs said first analyte in a first direction and a second analyte in a second direction.
96. The kit of claim 81 or 82 wherein said separation module comprises one or more two dimensional arrays of obstacles that define a plurality of gaps that direct flow unequally into subsequent gaps. 0 97. The kit of claim 81 wherein said prenatal diagnosis comprises determining sex of said fetus.
98. The kit of claim 81 wherein said prenatal diagnosis comprises determining the existence of trisomy 13.
99. The kit of claim 82 wherein said postnatal diagnosis comprises determining the existence or number of circulating nucleated red blood cells. 5 100. A business method for proving a prenatal diagnostic comprising: obtaining a blood sample of a mammal who is or has been pregnant with a fetus; enriching from said blood sample one or more fetal cells; analyzing said fetal cells to determine a condition of said fetus; and providing a report on said condition in exchange for a service fee. 0 101. The business method of claim 100 wherein said business licenses a CLIA laboratory to perform said analyzing step.
102. The business method of claim 100 wherein said enriching step is performed in a fluid system adapted to separate said fetal cell from maternal cells by directing said cells in different directions by size.
103. The business method of claim 100 wherein said business conducts said service. 35 104. The business method of claim 100 wherein said condition is selected from the group consisting of: trisomy 13, trisomy 18, trisomy 21 (Down Syndrome), Turner Syndrome (damaged X chromosome), Klinefelter Syndrome (XXY) and other irregular number of sex or autosomal chromosomes.
105. The business method of claim 100 wherein said condition is selected from the group consisting of: Wolf-Hirschhorn (4p-), Cri-du-chat (5p-), Williams syndrome (7ql 1.23), Prader-Willi syndrome (15ql 1.2-q13), 40 Angelman syndrome (15q 1.2-q13), Miller-Dieker syndrome (17p13.3), Smith-Magenis syndrome (17pl 1.2), DiGeorge and Velo-cardio-facial syndromes (22ql 1.2), Kallman syndrome (Xp22.3), Steroid Sulfatase Deficiency (STS) (Xp22.3), X-Linked Ichthiosis (Xp22.3), and Retinoblastoma (13q14). -45- WO 2007/035585 PCT/US2006/036202 I ,B:' "/ ,l[p 0 b Ield of claim 100 wherein said report is performed for a health care provider or a health insurance company.
107. The business method of claim 100 wherein said business licenses a CLIA laboratory to perform said enrichment step. 5 108. A business comprising commercializing a diagnostic product for conducting a prenatal screen for a genetic defect in a fetus, wherein said diagnostic product enriches fetal cells from a maternal blood sample.
109. The business method of claim 108 wherein said business manufactures said diagnostic product.
110. The business method of claim 108 wherein said diagnostic product is manufactured from a polymer material. 0 111. The business method of claim 108 wherein said diagnostic is disposable.
112. The business method of claim 108 wherein said diagnostic product selectively directs fetal cells in a direction away from maternal enucleated red blood cells.
113. The business method of claim 108 wherein said diagnostic product detects genetic abnormalities in said fetal cells. 5 114. The business method of claim 113 wherein said genetic abnormalities are detected using a label that binds nucleic acids.
115. The business method of claim 114 wherein said label is a fluorescence label.
116. The business method of claim 115 wherein said label is a colorimetric label.
117. A business method for isolating fetal cells from maternal blood comprising: 0 obtaining a blood sample of a mammal who is or has been pregnant with a fetus; and enriching from said blood sample one or more fetal cells in exchange for a fee. -46-
AU2006292394A 2005-09-15 2006-09-15 Systems and methods for enrichment of analytes Abandoned AU2006292394A1 (en)

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US11/229,332 2005-09-15
US11/229,328 US20070059718A1 (en) 2005-09-15 2005-09-15 Systems and methods for enrichment of analytes
US11/229,037 2005-09-15
US11/229,037 US20070059774A1 (en) 2005-09-15 2005-09-15 Kits for Prenatal Testing
US11/228,454 US20070059716A1 (en) 2005-09-15 2005-09-15 Methods for detecting fetal abnormality
US11/229,336 2005-09-15
US11/228,462 US20070059680A1 (en) 2005-09-15 2005-09-15 System for cell enrichment
US11/229,332 US20070059719A1 (en) 2005-09-15 2005-09-15 Business methods for prenatal Diagnosis
US11/228,454 2005-09-15
US11/228,462 2005-09-15
US11/229,336 US20070059781A1 (en) 2005-09-15 2005-09-15 System for size based separation and analysis
US11/229,328 2005-09-15
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