Clinically intelligent diagnostic devices and methods

• US 7,566,533 B2
• Filed: 03/08/2006
• Issued: 07/28/2009
• 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:
  US11/371,332
• Publication Number:
  US 20060240453A1
• Time in Patent Office: 1,238 Days
• Field of Search: 435/6, 435/7.1, 536/24.3
• 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 multiplexed test comprising two or more clusters of a probe or set of probes, wherein at least one probe detects in a biological sample from a subject at least one target that is indicative of a cause of at least one medical symptom, and wherein at least one probe detects a second target in the biological sample, wherein the second target is a genetic target comprising at least one sequence in the subject that makes the subject resistant, tolerant intolerant or susceptible to a therapeutic agent useful for treating the cause of the at least one medical symptom.

2. The multiplex test of claim 1, wherein the cause is selected from the group consisting of a pathogen, an infection, inflammation, autoimmunity, a neoplasm, and a drug.

3. The multiplex test of claim 1, wherein the cause is selected from the group consisting of iatrogenic, congenital, developmental inherited, environmental endocrine, metabolic and a combination thereof.

4. The multiplex test of claim 1, wherein the first target is selected from the group consisting of an antibody, an antigen, an enzyme, a cell, an endogenous genetic marker, a peptide, a polypeptide, a protein, a hapten, a glycoprotein, an aptamer, a small organic molecule, an inorganic molecule, a toxin, and a polysaccharide, or a combination thereof.

5. The multiplex test of claim 1, wherein the subject is an animal selected from the group consisting of a human, a bird, a dog, a cat, a cow, a pig, and a horse.

6. The multiplex test of claim 1, wherein the two or more clusters of a probe or set of probes is attached to a surface selected from the group consisting of:

a microfluidic device, a sequencing chip, a biochip, a microarray, a bead and a membrane comprising a material selected from the group consisting of nitrocellulose, nylon, polyethylene, polycarbonate, glass microfiber and gortex.

7. The multiplex test of claim 1, wherein the two or more clusters of a probe or set probes are contained in an array that is deposited on a multiplexed device.

8. A kit comprising

(a) two or more clusters of a probe or set of probes, wherein at least one probe detects in a biological sample from a subject at least one target that is indicative of a cause of at least one medical symptom, and wherein at least one probe for a second target detects in the biological sample at least one genetic sequence in a subject that makes the subject resistant, tolerant, intolerant or susceptible to a therapeutic agent useful for treating the cause of the at least one medical symptom;

and

(b) reagents and/or materials necessary for testing the sample.

9. The kit according to claim 8, wherein at least one of the clusters of a probe or set of probes detects at least one target associated with jaundice and/or liver failure.

10. The kit according to claim 9, wherein at least one of the clusters of a probe or set of probes detects at least five targets selected from the group consisting of anti-LKM-1 antibodies, anti-mitochondrial M2 antibodies, Hepatitis A virus, Hepatitis B virus, Hepatitis C virus, Hepatitis D virus, Hepatitis E virus, and CMV virus.

11. The kit according to claim 8, wherein at least one of the clusters of a probe or set of probes detects at least one of a mutation and/or allelic variant of the subject selected from the group consisting of Dubin-Johnson Syndrome, Hyperbilirubinemia Type I, Acute Hepatic Porphyria, Delta-Aminolevulinate Dehydratase Deficiency, Porphobilinogen Synthase Deficiency Alagille Syndrome, Arteriohepatic Dysplasia, Cholestasis with Peripheral Pulmonary Stenosis, Alpha-1-Antitrypsin Deficiency, Carbamoylphosphate Synthetase I Deficiency, Carbamyl Phosphatase Deficiency, Carbamyl Phosphate Synthetase Deficiency, Carnitine-Acylcarnitine Translocase Deficiency, Citrullinemia, Ferrochelatase Deficiency, Heme Synthetase Deficiency, fatty Acid Oxidation Disorder, Unspecified, Fructose 1,6 Bisphosphatase Deficiency, Galactosemia, Galactose Epimerase Deficiency, Galactose-1-Phosphate Uridyltransferase Deficiency, NGlutaricacidemia Type II, Glutaricaciduria Type II, Glycogen Storage Disease Type I/Ia, Glucose-6-Phosphatase Deficiency, Von Gierke Disease, Glycogen Storage Disease Type III, Cori Disease, Debrancher Deficiency, Forbe Disease, Glycogen Storage Disease Type IV, Brancher Deficiency, Glycogen Storage Disease Type IX, Glycogen Storage Disease Type VIII, Phosphorylase Kinase Deficiency of Liver, Glycogen Storage Disease Type Ib, Glucose-6-Phosphate Translocase Defect, Glycogen Storage Disease Type VI, HERS Disease, Hereditary Coproporphyria, Coproporphyrinogen Oxidase Deficiency, Harderoporphyria, Hereditary Fructose Intolerance, Fructosemia, Hereditary Hemochromatosis, Long Chain 3-hydroxyacyl-CoA Dehydrogenase Deficiency, Acute Fatty Liver, Disease of Pregnancy, HELLP, Hemolysis, Enzymes, and Low Platelets, LCHAD Deficiency, Trifunctional Protein Deficiency, Long Chain Acyl-CoA Dehydrogenase Deficiency, LCAD Deficiency, Medium Chain 3-Ketothiolase Deficiency, MCKAT Deficiency, Medium Chain Acyl-Coenzyme A Dehydrogenase Deficiency, MCAD Deficiency, Mucopolysaccharidosis Type II, Hunter Syndrome, MPS II, Mucopolysaccharidosis Type IIIB, MPS IIIB, Sanfilippo Syndrome Type B, Mucopolysaccharidosis Type IIIC, MPS IIIC, Sanfilippo Syndrome Type C, Mucopolysaccharidosis Type IVB, MPS IVB, Morquio Syndrome Type B, Mucopolysaccharidosis Type VI, Arylsulfatase B Deficiency, MPS VI, Maroteaux, Lamy Syndrome, Mucopolysaccharidosis Type VII, Glucuronidase Deficiency MPS, MPS VII, Sly Syndrome, Niemann-Pick Disease Without Sphingomyelinase Deficiency, Niemann-Pick Disease Type C, Niemann-Pick Disease Type D, Niemann-Pick Disease, Nova Scotian Type, Ornithine Transcarbamylase Deficiency, OTC Deficiency, Phosphorylase Kinase Deficiency of Liver and Muscle, Polycystic Kidney Disease, Recessive, ARPKD, PKD, Infantile, PKD, Recessive, Salla Disease, Sialic Acid Storage Disease, Sialidosis, Glycoprotein Neuraminidase Deficiency, ML I, ML1, Mucolipidosis, Wilson Disease, Wolman Disease, Cholesterol Ester Storage Disease, and/or Zellweger syndrome, and Cerebrohepatorenal Syndrome.

12. The kit according to claim 8, wherein at least one of the clusters of a probe or set of probes detects at least one target associated with pharyngitis.

13. The kit according to claim 12, wherein at least one of the clusters of a probe or set of probes detects at least five targets selected from the group consisting of a virus, a bacteria, a mycoplasma, and an antibody to a pathogen.

14. The kit according to claim 13, wherein the virus is selected from the group consisting of Rhinovirus, Coronavirus, Adenovirus types 3, 4, 7, and 14, Herpes simplex virus types 1 and 2, Parainfluenza virus types 1-4, Influenza virus types A and B, Coxsackievirus A types 2, 4-6, 8, and 10, Epstein-Bar virus, Cytomegalovirus, and HIV-1.

15. The kit according to claim 13, wherein the bacteria is selected from the group consisting of Streptococcus pyogenes (group A beta-hemolytic streptococci), Group C beta-hemolytic streptococci Neisseria gonorrhoeae, Corynebacterium diphtheriae, Corynebacterium ulcerans, Arcanobacterium haemolyticum (Corynebacterium haemolyticum), Yersinia enterocolitica, Treponema pallidum, and Chlamydia pneumoniae.

16. The kit according to claim 13, wherein the mycoplasma is selected from the group consisting of Mycoplasma pneumoniae and Mycoplasma hominis (type 1).

17. The kit according to claim 8, wherein at least one of the clusters of a probe or set of probes detects at least one target associated with lower respiratory tract symptoms.

18. The kit according to claim 17, wherein the lower respiratory tract symptoms are selected from the group consisting of cough, fever, chest discomfort, dyspnea, pneumonia, and a combination thereof.

19. The kit according to claim 8, wherein at least one of the clusters of a probe or set of probes detects causative agents related to biological warfare or terrorism.

20. The kit according to claim 8, wherein at least one of the clusters of a probe or set of probes detects at least one target associated with headache, fever, meningismus, nausea, vomiting, rigors, profuse sweating, weakness, myalgias, and photophobia.

21. The kit according to claim 20, wherein the second target is a genetic marker selected from the group consisting of C5, C6, C7, C8, C9, and Properidin.

22. The kit according to claim 20, wherein the at least one target is a therapeutic marker selected from the group consisting of beta-lactamase and cytochrome P450.

23. The kit according to claim 8, wherein at least one of the clusters of a probe or set of probes detects at least one target associated with diarrhea.

24. The kit according to claim 8, wherein at least one of the clusters of a probe or set of probes detects at least one target associated with septicemia.