Digital lspr for enhanced assay sensitivity

Abstract

Techniques for detecting a presence of an analyte and determining a concentration of analytes are provided. An analyte may be provided on an LSPR-active surface. The LSPR-active surface may comprise sensitivity enhancing labels. The analyte may induce a local change near the LSPR-active surface. The LSPR-active surface may be imaged with an imaging device for images before, during, or after a reaction takes place. Local regions of interest within the images may be analyzed to detect the local changes.

What is claimed is: 
     
         1 . A system, comprising:
 a processor; and   a memory containing a program that, when executed on the processor, performs an operation, the operation comprising:
 randomly selecting a plurality of corresponding regions of interest in each of a series of two or more images of a nanostructured sensor surface, wherein the nanostructured sensor surface is capable of sustaining a localized surface plasmon resonance; 
 measuring a change in RGB value or greyscale value for each of the plurality of corresponding regions by comparing the RGB value or greyscale value for corresponding regions of interest in different images of the series of two or more images; and 
 determining a presence of an analyte based on analyzing the measured changes in RGB value or greyscale value for the plurality of corresponding regions. 
   
     
     
         2 . The system of  claim 1 , wherein a limit of detection for determining the presence of the analyte is determined to be better than 1 ng/mL based on analyzing a control reading and one or more readings corresponding to one or more known quantities or concentations of the analyte. 
     
     
         3 . The system of  claim 1 , wherein a limit of detection for determining the presence of the analyte is determined to be better than 1 pg/mL based on analyzing a control reading and one or more readings corresponding to one or more known quantities or concentations of the analyte. 
     
     
         4 . The system of  claim 1 , the operation further comprising determining a concentration of the analyte based on the measured changes in RGB value or greyscale value. 
     
     
         5 . The system of  claim 1 , wherein the measured change in RGB value or greyscale value is a change in RGB value or greyscale value of light reflected from the nanostructured sensor surface. 
     
     
         6 . The system of  claim 1 , wherein the series of two or more images are captured before and after a local analyte-induced change occurs. 
     
     
         7 . The system of  claim 1 , further comprising a fluidic system for delivery of a sample and assay reagents to the nanostructured sensor surface, wherein the assay reagents comprise a primary binding component and a secondary binding component, and wherein the secondary binding component comprises a sensitivity enhancing label. 
     
     
         8 . The system of  claim 7 , wherein the sensitivity enhancing label is at least one of: (i) an enzyme that catalyzes a conversion of a reactant to an insoluble product, or (ii) a metallic nanoparticle that is capable of inducing plasmon-plasmon coupling between the metallic nanoparticle and the nanostructured sensor surface. 
     
     
         9 . The system of  claim 1 , wherein the analyte is present in a sample an amount of 100 ng/mL or less. 
     
     
         10 . The system of  claim 1 , wherein the analyte is present in a sample in an amount of 1 pg/mL or less. 
     
     
         11 . The system of  claim 1 , the operation further comprising receiving a report comprising a result of the operation and making a healthcare decision based on the reported result, wherein the sample is a patient sample. 
     
     
         12 . The system of  claim 1 , wherein the nanostructured sensor surface comprises a continuous nanostructured metallic thin film across a sensor substrate. 
     
     
         13 . The system of  claim 1 , wherein determining the presence of the analyte comprises:
 analyzing measured changes in RGB value and intensity of light for the plurality of corresponding regions, and wherein the measured changes in RGB value and intensity of light for the plurality of corresponding regions are based on comparing the RGB value and intensity of light for corresponding regions of interest in different images of the series of two or more images.   
     
     
         14 . The system of  claim 1 , wherein the nanostructured sensor surface comprises: a first metallic thin film layer, a second metallic thin film layer, and a dielectric layer at least partially between the first metallic thin film layer and the second metallic thin film layer. 
     
     
         15 . The system of  claim 1 , wherein the nanostructured sensor surface comprises: a first plurality of metallic thin film layers, a second plurality of metallic thin film layers, and a dielectric layer at least partially between the first plurality of metallic thin film layers and the second plurality of metallic thin film layers. 
     
     
         16 . A computer program product, comprising:
 a non-transitory computer-readable storage medium having computer-readable program code embodied therewith, the computer-readable program code executable by one or more computer processors to perform an operation, the operation comprising:
 randomly selecting a plurality of corresponding regions of interest in each of a series of two or more images of a nanostructured sensor surface, wherein the nanostructured sensor surface is capable of sustaining a localized surface plasmon resonance; 
 measuring a change in RGB value or greyscale value for each of the plurality of corresponding regions by comparing the RGB value or greyscale value for corresponding regions of interest in different images of the series of two or more images; and 
 determining a presence of an analyte based on analyzing the measured changes in RGB value or greyscale value for the plurality of corresponding regions. 
   
     
     
         17 . The computer program product of  claim 16 , wherein a limit of detection for determining the presence of the analyte is determined to be better than 1 pg/mL based on analyzing a control reading and one or more readings corresponding to one or more known quantities or concentations of the analyte, the operation further comprising:
 determining a concentration of the analyte based on the measured changes in RGB value or greyscale value.   
     
     
         18 . The computer program product of  claim 16 , wherein the nanostructured sensor surface comprises a continuous nanostructured metallic thin film across a sensor substrate. 
     
     
         19 . The computer program product of  claim 16 , wherein the change in RGB value is measured according to the formula D=√{square root over ((ΔR) 2 +(ΔG) 2 +(ΔB) 2 )} wherein ΔR, ΔG, and ΔB correspond to changes in red, green and blue pixel values in the corresponding regions of interest in images that have been adjusted for changes in local illumination intensity. 
     
     
         20 . A system, comprising:
 a fluidic system for delivery of a sample and assay reagents to a nanostructured sensor surface, wherein the assay reagents comprise a primary binding component and a secondary binding component, wherein the secondary binding component comprises a sensitivity enhancing label, and wherein the nanostructured sensor surface comprises a continuous nanostructured metallic thin film across a sensor substrate;   a processor; and   a memory containing a program that, when executed on the processor, performs an operation, the operation comprising:
 randomly selecting a plurality of corresponding regions of interest in each of a series of two or more images of the nanostructured sensor surface, wherein the nanostructured sensor surface is capable of sustaining a localized surface plasmon resonance; 
 measuring a change in RGB value or greyscale value for each of the plurality of corresponding regions by comparing the RGB value or greyscale value for corresponding regions of interest in different images of the series of two or more images; and 
 determining a presence of an analyte based on analyzing the measured changes in RGB value or greyscale value for the plurality of corresponding regions.