Assay accuracy improvement

Abstract

One aspect of the present invention is to provide systems and methods that improve the accuracy of an assay that comprise at least one or more parameters each having a random error.

We claim: 
     
         1 . A system for assaying a sample with one or more operation conditions, comprising:
 a) load the sample to a sample holding device, e.g. a QMAX device, whose gap is in proportion to the size of the analyte to be analyzed or the analytes form a mono-layer between the gap;   b) take an image of the sample in the sample holding device on the area-of-interest (AoI) for assaying with an imager;   c) segment the image of the sample taken by the said imager from (b) into equal-sized and non-overlapping sub-image patches (e.g. 8×8 equal-sized small image patches);   d) perform machine learning based inference with a trained machine learning model for analyte detection and segmentation on each image patch—to determine and not limited to the analyte count and concentration thereof;   e) sort the analyte concentration of the constructed sub-image patches in ascending order and determine the 25% quantile Q1 and 75% quantile Q3 thereof;   f) determine the uniformity of the analytes in the image of the sample with an inter-quantile-range based confidence measure: confidence-IQR=(Q3−Q1)/(Q3+Q1); and   g) if the confidence-IQR from (f) exceeds a certain threshold (e.g. 30%), indicating an error or defect and the assay result is not trustworthy, wherein the said threshold is derived from the training/evaluation data or from the physical rules that govern the distribution of the analytes.   
     
     
         2 . An apparatus for improving accuracy of an assay that has one or more operation conditions unpredictable and random, comprising:
 (1) a detection device that detects an analyte in a sample to generate a detection result, wherein the sample contains or is suspected of containing the analyte;   (2) a checking device that checks trustworthiness of a particular detection result generated by the detection device, comprising:   (i) an imager that is capable of taking one or more images of (1) a portion of the sample and/or (2) a portion of the detection instrument that is surrounded the portion of the sample, wherein the images substantially represent the conditions that the portion of the sample is measured in generating detection result in step (a); and   (ii) a computing unit with an algorithm that is capable of analyzing the features in the images taken in step (b)(i) to determine a trustworthiness of the detection result;   (c) discarding the detection result generated in step (a), if the step (b) determines the detection result is untrustworthy;   wherein the step (a) has one or more operation conditions that is unpredictable and random.   
     
     
         3 . A device for assaying an analyte present in a sample under one or more operational variables, comprising:
 (a) a solid surface having a sample contact area for receiving a thin layer of a sample, the sample containing an analyte to be measured;   (b) an imager configured to image a portion of the sample contact area where the analyte is measured; and   (c) a non-transitory computer readable medium having an instruction that, when executed, it performs the determination of trustworthy of the assay result by analyzing the operational variables displayed in the image of the portion of the sample.