Systems and Methods for Developing Diagnostic Tests Based on Biomarker Information from Legacy Clinical Sample Sets

Abstract

Disclosed are systems and methods for developing diagnostic tests (e.g., detection, screening, monitoring, and prognostic tests) based on biomarker information from legacy clinical sample sets, for which only small sample volumes (e.g., about 0.05 to about 1.0 mL or less per sample) are typically available. For example, biomarkers (e.g., about 10, 50, 100, 150, 200, 300, or more) may be detected in the clinical samples through the use of single molecule detection and each biomarker may be detected in an assay that includes about 1 μL or less of a legacy clinical sample.

1 - 40 . (canceled) 
     
     
         41 . A single detection means of evaluating the health state of a human subject, comprising obtaining a measurement of at least one clinical biomarker from at least one live clinical sample isolated from said human subject, and inputting said measurement(s) into a model that calculates an output value correlated to said health state, the improvement comprising using as said model an algorithm that was developed by measurement of multiple development biomarkers comprising said clinical biomarker(s) from at least one legacy clinical sample set annotated for said health state, said measurement comprising use of legacy clinical samples having a sample volume of 1 ml or less, and analyzing said measurement of multiple biomarkers for an association with said health state. 
     
     
         42 . The means of  claim 41 , wherein said measurement of multiple development biomarkers comprises measuring at least two biomarkers from said sample volume. 
     
     
         43 . The means of  claim 42 , wherein said measurement of multiple development biomarkers comprises measuring at least 10 biomarkers from a sample volume less than about 0.5 milliliters. 
     
     
         44 . The means of  claim 42 , wherein said measurement of multiple development biomarkers comprises measuring at least 20 biomarkers from said sample volume. 
     
     
         45 . The means of  claim 42 , wherein said measurement of multiple development biomarkers comprises measuring at least 100 biomarkers from said sample volume. 
     
     
         46 . The means of  claim 42 , wherein said measurement of multiple development biomarkers comprises measuring at least 200 biomarkers from said sample volume. 
     
     
         47 . The means of  claim 42 , wherein said measurement of multiple development biomarkers comprises measuring at least 300 biomarkers from said sample volume. 
     
     
         48 . The means of  claim 41 , wherein said measurement of multiple development biomarkers comprises, for each biomarker, measuring said biomarker in an assay of said legacy clinical sample, wherein said assay used about 1 microliter (μL) or less of said sample volume for each biomarker. 
     
     
         49 . The means of  claim 48 , wherein at least 10 development biomarkers are measured per legacy clinical sample. 
     
     
         50 . The means of  claim 48 , wherein said measurement of multiple development biomarkers uses single molecule detection to measure said multiple development biomarkers in said legacy clinical sample. 
     
     
         51 . The means of  claim 50 , wherein said measurement of biomarkers in the legacy clinical sample by single molecule detection consists of dynamic quantitation. 
     
     
         52 . The means of  claim 41 , wherein said health state is the presence or absence of a disease. 
     
     
         53 . The means of  claim 41 , wherein said health state is pre-disease or a pre-disease condition. 
     
     
         54 . The means of  claim 41 , wherein said health state is the risk of developing a disease. 
     
     
         55 . The means of  claim 52 , wherein said absence of a disease is further defined to be a normal state or pre-disease state. 
     
     
         56 . The means of  claim 41 , wherein said biomarkers comprise traditional laboratory risk factors. 
     
     
         57 . The means of  claim 41 , wherein said live clinical sample isolated from said human subject is whole blood, serum, plasma, blood cells, endothelial cells, tissue biopsies, lymphatic fluid, ascites fluid, interstitial fluid, bone marrow, cerebrospinal fluid, saliva, sputum, sweat, or urine. 
     
     
         58 . The means of  claim 57 , wherein said live clinical sample is plasma or serum. 
     
     
         59 . The means of  claim 57 , wherein said sample is from a human subject undergoing one or more treatment regimens. 
     
     
         60 . The means of  claim 59 , wherein said treatment regimens are selected from a group consisting of therapeutics, prophylactics, exercise regimens, dietary supplementation, weight loss, surgical intervention, device implantation and exercise regimens.