Clinically intelligent diagnostic devices and methods

• US 6,905,816 B2
• Filed: 11/27/2001
• Issued: 06/14/2005
• Est. Priority Date: 11/27/2000
• Status: Expired due to Fees

• Current Assignee: Intelligent Medical Devices, Inc.
• Original Assignee: Intelligent Medical Devices, Inc.
• Inventors: Nikolic, Boris, Jacobs, Alice A., Gupta, Vineet
• Primary Examiner(s): Horlick, Kenneth R.
• Application Number:
  US09/996,056
• Publication Number:
  US 20020095073A1
• Time in Patent Office: 1,295 Days
• Field of Search: 435/6, 435/7.1, 435/91.1, 435/91.2, 435/287.2, 536/22.1, 536/23.1, 536/24.33
• US Class Current: 435/5
• CPC Class Codes: B01F 33/3036 using a biological motor, i.e. biological molecules which are activated and movement is induced to stir a fluid
• CPC Class Codes: B01F 33/45 Magnetic mixers; Mixers with magnetically driven stirrers
• CPC Class Codes: B01F 33/451 wherein the mixture is directly exposed to an electromagnetic field without use of a stirrer, e.g. for material comprising ferromagnetic particles or for molten metal
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00481 by the use of moving stirrers within the reaction vessels
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• CPC Class Codes: B01J 2219/00509 Microcolumns
• CPC Class Codes: B01J 2219/00511 Walls of reactor vessels
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00547 Bar codes
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00619 using hydrophilic or hydrophobic regions
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/0063 : Other, e.g. van der Waals forces, hydrogen bonding
• CPC Class Codes: B01J 2219/00637 : by coating it with another layer
• CPC Class Codes: B01J 2219/00644 : the porous medium being present in discrete locations, e.g. gel pads
• CPC Class Codes: B01J 2219/00659 : Two-dimensional arrays
• CPC Class Codes: B01J 2219/00662 : Two-dimensional arrays within two-dimensional arrays
• CPC Class Codes: B01J 2219/00664 : Three-dimensional arrays
• CPC Class Codes: B01J 2219/00677 : Ex-situ synthesis followed by deposition on the substrate
• CPC Class Codes: B01J 2219/00689 : using computers
• CPC Class Codes: B01J 2219/00702 : Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/0072 : Organic compounds
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01J 2219/00725 : Peptides
• CPC Class Codes: B01J 2219/00731 : Saccharides
• CPC Class Codes: B01J 2219/0074 : Biological products
• CPC Class Codes: B01J 2219/00745 : Inorganic compounds
• CPC Class Codes: B01L 2300/021 : Identification, e.g. bar codes
• CPC Class Codes: B01L 2300/0636 : Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/069 : Absorbents; Gels to retain a fluid
• CPC Class Codes: B01L 2300/0819 : Microarrays; Biochips
• CPC Class Codes: B01L 2300/0864 : comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 3/5027 : 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 B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/5085 : for multiple samples, e.g. microtitration plates
• CPC Class Codes: B01L 3/50857 : using arrays or bundles of open capillaries for holding samples
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C12Q 1/6837 : using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 40/12 : Libraries containing saccharides or polysaccharides, or derivatives thereof
• CPC Class Codes: C40B 40/18 : Libraries containing only inorganic compounds or inorganic materials
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: C40B 70/00 : Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
• CPC Class Codes: G01N 33/53 : Immunoassay; Biospecific binding assay; Materials therefor
• CPC Class Codes: G01N 33/543 : with an insoluble carrier for immobilising immunochemicals
• CPC Class Codes: G01N 33/54366 : Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/6803 : General methods of protein analysis not limited to specific proteins or families of proteins
• CPC Class Codes: G01N 33/6845 : Methods of identifying protein-protein interactions in protein mixtures

Abstract

The invention relates to the clinically intelligent design of diagnostic devices (such as microarrays) and methods of making and using such devices in differential diagnoses of specific clinical symptoms or sets of symptoms. In one aspect, the devices include various probes used to perform parallel screening of a number of analytes. The probes are clustered on the devices based on known clinical presentations of symptoms associated with specific diseases and disorders.

Claims

1. A method of determining a cause of one or more medical symptoms exhibited by a subject, the method comprising:

(a) obtaining one or more biological samples from the subject;

(b) obtaining an array of different probes or different sets of probes, wherein each probe or set of probes selectively interacts with a target associated with a different known cause of the one or more medical symptoms, and wherein the array includes at least

(i) a first probe or set of first probes directed to a first target, wherein the first target comprises one or more markers for one or more infectious agents known to cause the one or more medical symptoms; and

(ii) a second probe or set of second probes directed to a second target, wherein the second target comprises one or more genetic markers of the subject or one or more biological or chemical molecules, all known to be a cause of the one or more medical symptoms;

(c) applying the one or more biological samples to the probes in the array under conditions that enable all of the probes to selectively interact with any targets in the biological sample;

(d) detecting interactions; and

(e) analyzing interactions to determine a cause of the one or more medical symptoms.

2. The method of claim 1, wherein the array of probes or sets of probes is arranged on a planar substrate.

3. The method of claim 1, wherein each target is a nucleic acid, peptide, polypeptide, protein, antibody, antigen, small organic molecule, inorganic molecule, enzyme, or polysaccharide.

4. The method of claim 1, wherein the array of probes comprises nucleic acid probes and polypeptide probes.

5. The method of claim 1, wherein all of the probes in the array are polypeptides.

6. The method of claim 5, wherein the probes are antibodies, antigens, enzymes, zinc-finger binding proteins, minor-groove binders, transcriptional factors, combinations thereof, or chimeras thereof.

7. The method of claim 1, wherein the subject is a plant or animal.

8. The method of claim 1, wherein the subject is a human.

9. The method of claim 1, wherein the subject is deceased.

10. The method of claim 1, wherein the array includes four or more different probes or sets of probes, wherein each probe or set of probes is directed to a different target, and wherein the different first and second targets comprise at least a marker for a virus, a marker for a bacteria, a biological molecule, and a genetic marker of the subject.

11. The method of claim 1, wherein the biological sample is a blood, cerebrospinal fluid, cell culture, urine, sweat, buccal swab, tissue biopsy, or aspiration sample.

12. The method of claim 2, wherein the probes are attached to the substrate using covalent or non-covalent bonds.

13. The method of claim 2, wherein the probes are attached to the substrate using amide or thiol bonds.

14. The method of claim 1, wherein the probes are expressed on the surface of genetically modified cells.

15. The method of claim 1, wherein a probe selectively interacts with a target by specifically binding to the target to form a complex.

16. The method of claim 1, wherein a first probe selectively interacts with a target associated with an infectious disease caused by a bacteria, virus, or fungus, and a second, different probe selectively interacts with a target associated with a genetic cause.

17. The method of claim 1, wherein the array of probes further comprises probes that assay for the absence of a causative agent of one or more medical symptoms.

18. A method of claim 1, wherein all of the probes selectively interact with their respective targets under the same conditions.

19. The method of claim 1, wherein the array of probes comprises nucleic acid probes.

20. The method of claim 1, wherein all of the probes in the array are nucleic acid probes.

21. The method of claim 1, wherein the array further comprises a third probe or set of third probes directed to a third target, wherein the third target comprises a marker for a therapeutic optimization factor of the subject, a marker for a therapeutic optimization factor of the first target, or both.

22. The method of claim 1, wherein the biological or chemical molecule is a cancer marker, vascular marker, inflammatory marker, endocrine marker, metabolic marker, or autoimmune marker.

23. The method of claim 1, wherein the biological or chemical molecule is an immunoglobulin, self-antigen, or antigen.

24. The method of claim 1, wherein the biological or chemical molecule is a poison, drug, or a small organic or inorganic molecule.

25. The method of claim 1, wherein the infectious agent is a virus, bacteria, fungus, or pathogenic plant.

26. The method of claim 1, further comprising determining the susceptibility of the subject to a cause of the one or more medical symptoms;

wherein the array further includes a third probe or set of third probes directed to a third target, wherein the third target comprises one or more genetic markers or proteins associated with the susceptibility of the subject to a cause of the one or more medical symptoms; and

wherein analyzing further comprises analyzing interactions to determine the susceptibility of the subject to a cause of the one or more medical symptoms.

27. The method of claim 1, further comprising assessing the suitability of one or more therapeutic agents to treat the cause of the one or more medical symptoms;

wherein the array further includes a third probe or set of third probes directed to a third target, wherein the third target comprises one or more markers for one or more therapeutic optimization factors; and

wherein analyzing further comprises analyzing interactions to determine the suitability of a therapeutic agent to treat a cause of the one or more symptoms.

28. The method of claim 27, wherein the third target comprises one or more markers for one or more therapeutic optimization factors for (i) two or more of the first target, (ii) two or more of the second target, or (iii) one or more of each of the first and second targets.

29. The method of claim 26, further comprising assessing the suitability of one or more therapeutic agents to treat the cause of the one or more medical symptoms;

wherein the array further includes a fourth probe or set of fourth probes directed to a fourth target, wherein the fourth target comprises one or more markers for one or more therapeutic optimization factors; and

wherein analyzing further comprises analyzing interactions to determine the suitability of a therapeutic agent to treat a cause of the one or more symptoms.

30. The method of claim 27, wherein the therapeutic optimization factor is tolerance, intolerance, or susceptibility of the subject or an infectious agent to a specific drug.

31. The method of claim 27, wherein the marker for the therapeutic optimization factor is a gene in a pathogen that causes susceptibility, resistance, or an idiosyncratic reaction of the pathogen when exposed to a therapeutic agent.