Quality assurance/quality control for high throughput bioassay process

• US 7,333,896 B2
• Filed: 07/28/2003
• Issued: 02/19/2008
• Est. Priority Date: 07/29/2002
• Status: Expired due to Fees

• Current Assignee: Department Of Health And Human Services National Institutes Of Health, Vermillion, Inc.
• Original Assignee: Correlogic Systems, Inc. (Aspira Women's Health, Inc.), United States Department Of Health And Human Services
• Inventors: Petricoin, Emanuel F. III, Hitt, Ben A., Levine, Peter J.
• Primary Examiner(s): Clow; Lori A.
• Application Number:
  US10/628,137
• Publication Number:
  US 20040058388A1
• Time in Patent Office: 1,667 Days
• Field of Search: None
• US Class Current: 702/19
• CPC Class Codes: C40B 30/04 by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
• CPC Class Codes: G01N 33/6803 General methods of protein analysis not limited to specific proteins or families of proteins
• CPC Class Codes: G01N 33/6848 Methods of protein analysis involving mass spectrometry
• CPC Class Codes: G16B 25/00 ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• CPC Class Codes: G16B 40/00 ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• CPC Class Codes: G16B 40/10 Signal processing, e.g. from mass spectrometry [MS] or from PCR
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

The present invention relates to a method of quality assurance/quality control for high-throughput bioassay processes. The method includes generating a bioassay process model, and then comparing spectral data based on a combination of a biochip and a test serum to the bioassay process model to determine if the test sample and the bioassay process are producing acceptable data. Alternatively, the method may include comparing spectral data based on a combination of serum and diluents used in an electrospray process to the bioassay process model. If the bioassay process and test sample fall within the model, then the spectrum produced may be further analyzed.

Claims

1. A method of determining whether mass spectral data from a test serum is acceptable for analysis in a bioassay using biochips, comprising:

selecting a diverse group of sera, the diverse group of sera having different characteristics;

obtaining information associated with a mass spectrum of each of the sera from the diverse group of sera using each of a plurality of control biochips;

generating a control model based at least in part on the spectra obtained from the diverse group of sera, the control model including at least one centroid located in an n-dimensional space defined by n mass spectral features included in the control model;

performing mass spectrometry on a test serum applied to a test biochip to obtain a test spectrum associated with the test serum;

mapping the test spectrum to the n-dimensional space; and

certifying that the test spectrum is acceptable for analysis in the bioassay if it is determined that the test spectrum maps to the n-dimensional space within an acceptable distance from said at least one centroid in the control model.

2. The method of claim 1, further comprising:

classifying a biological state from the test spectrum based on a predetermined biological state model.

3. The method of claim 1, wherein if the test spectrum does not map to the n-dimensional space within an acceptable distance from said at least one centroid in the control model, and the test biochip is a first biochip, the method further comprising:

repeating the steps of performing and mapping for a second biochip different from said test biochip.

4. The method of claim 1, said selecting further comprising:

selecting at least two different sera from a pool of diverse sera, the pool of diverse sera consisting of;

sera from healthy males, sera from healthy females, sera from males afflicted with a disease, sera from females afflicted with a disease, sera from persons of different races, and sera from people of different ages.

5. The method of claim 1, wherein said generating includes:

identifying at least one cluster in common to the sera of the diverse group of sera and the plurality of different control biochips that contains said at least one centroid in the control model; and

certifying that the test spectrum is acceptable for analysis in the bioassay if it is determined that the test spectrum maps to the n-dimensional space within said at least one cluster.

6. The method of claim 1, wherein the obtaining information includes:

obtaining information on sera applied to at least two types of biochips, the types of biochips being at least two of a cationic exchange biochip, an anionic exchange biochip, and an immobilized metal biochip.

7. The method of claim 1, wherein the test biochip is one of the plurality of different biochips.

8. The method of claim 1, wherein the test biochip is not one of the plurality of different biochips.

9. A method of determining whether mass spectral data from a test serum is acceptable for analysis in a bioassay employing a control model generated based on mass spectra obtained from application of a plurality of different sera to a plurality of different biochips, the control model including at least one centroid located in an n-dimensional space defined by n mass spectral features included in the model, comprising:

applying a test serum to a spot on a test biochip;

performing mass spectrometry on the test serum to obtain test spectral data associated with the test serum and the test biochip; and

mapping the test spectrum to the n-dimensional space; and

certifying that the test spectrum is acceptable for analysis in the bioassay if it is determined that the test spectrum maps to the n-dimensional space within an acceptable distance from said at least one centroid in the control model.

10. The method of claim 9, further comprising:

classifying a biological state from the test spectrum based on a predetermined biological state model.

11. The method of claim 9, wherein said performing mass spectrometry includes performing surface enhanced laser desorption/ionization time of flight (SELDI-TOF) mass spectrometry.

12. The method of claim 9, wherein said bioassay is capable of determining if the test serum exhibits a disease state.

13. A method of determining whether mass spectral data from a test serum is acceptable for analysis in a bioassay using a biochip, comprising:

providing in an n-dimensional space defined by n mass spectral features a location of at least one centroid associated with one biochip and that distinguishes the one biochip from at least one second biochip;

generating a test mass spectrum from the application of a test serum to a test biochip;

mapping the test mass spectrum to the n-dimensional space; and

certifying that the test mass spectrum is acceptable for analysis in the bioassay if it is determined that the test mass spectrum maps to the n-dimensional space within an acceptable distance from the at least one centroid.

14. A method of determining whether mass spectral data from a test sample is acceptable for analysis in a bioassay that generates mass spectral data from the application of a sample to a biochip, comprising:

providing a location in an n-dimensional space defined by n mass spectral features of at least one centroid in the model associated with a biochip;

receiving mass spectral data associated with the test sample;

providing a location in the n-dimensional space of at least one test centroid associated with the mass spectral data from the test sample;

comparing the at least one test centroid to the at least one centroid in the model to determine the displacement in the n-dimensional space of the at least one test centroid from the at least one centroid in the model; and

certifying to a user that the mass spectral data from the test sample is acceptable for analysis in the bioassay if it is determined that the displacement is within an acceptable distance.

15. The method of claim 14, wherein the sample is serum.

16. The method of claim 14, wherein the mass spectral data is generated by surface enhanced laser desorption/ionization time of flight (SELDI-TOF) mass spectrometry.

17. The method of claim 14, wherein the biochip is selected from the group consisting of a cationic exchange biochip, an anionic exchange biochip and an immobilized metal biochip.

18. A method of determining whether mass spectral data from a test sample is acceptable for analysis in a bioassay that generates mass spectral data from a sample that is applied to a biochip, comprising:

providing a location in an n-dimensional space defined by n mass spectral features of at least one centroid in a model associated with a biochip;

receiving mass spectral data associated with the test sample;

providing a location in the n-dimensional space of at least one test centroid associated with the mass spectral data from the test sample;

comparing the at least one test centroid to the model to determine the displacement in the n-dimensional space of the at least one test centroid from the at least one centroid in the model; and

certifying to a user that the mass spectral data from the test sample is acceptable for analysis in the bioassay if it is determined that the magnitude of the displacement is acceptable.

19. The method of claim 18, wherein the test sample is accepted for analysis if the displacement of the at least one test centroid from the at least one centroid in the model is within an acceptable distance.

20. The method of claim 18, wherein the sample is serum.

21. The method of claim 18, wherein the mass spectral data is generated by surface enhanced laser desorption/ionization time of flight (SELDI-TOF) mass spectrometry.

22. A method of evaluating results for a bioassay that generates mass spectral data from the application of a serum to a biochip, comprising:

selecting a diverse group of sera, the diverse group of sera having different characteristics;

selecting a control biochip of a predetermined type;

obtaining information associated with a mass spectrum of each of the sera from the diverse group of sera using the control biochip;

generating a model based at least in p art on the spectra obtained from the diverse group of sera, the model including at least one centroid located in an n-dimensional space defined by n mass spectral features included in the model;

performing mass spectrometry on a test serum applied to a test biochip to obtain a test spectrum associated with the test serum;

mapping the test spectrum obtained from said performing to the n-dimensional space; and

certifying that the test biochip is acceptable for use in the bioassay if the test spectrum maps to the n-dimensional space within an acceptable distance from the at least one centroid in the model.

23. The method of claim 22, wherein the control biochip is selected from the group consisting of a cationic exchange biochip, an anionic exchange biochip, and an immobilized metal biochip.

24. A method of evaluating results for a biological diagnostic test employing a model generated based on mass spectra obtained from application of a plurality of different sera to a preferred biochip, the model including at least one centroid located in an n-dimensional space defined by n mass spectral features included in the model, comprising:

applying a test serum to a spot on a test biochip;

performing mass spectrometry on the test serum to obtain test spectral data associated with the test serum and the test biochip; and

mapping the test spectrum to the n-dimensional space; and

certifying that the test biochip is acceptable for use in the biological diagnostic test if the test spectrum maps to the n-dimensional space within an acceptable distance from the at least one centroid in the model.

25. The method of claim 24, wherein the certifying includes evaluating the test spectrum in the biological diagnostic test to determine if the test serum exhibits a particular biological state.

26. The method of claim 24, wherein said performing mass spectrometry includes performing surface enhanced laser desorption/ionization time of flight (SELDI-TOF) mass spectrometry.

27. The method of claim 24, wherein said biological diagnostic test is a disease model capable of determining if the test serum exhibits a disease state associated with the disease model.