Metal-antibody tagging and plasma-based detection

Abstract

Various techniques for characterizing a target within a sample are described. An example method includes applying, to the sample, a recognition construct that includes a metal and a scaffold, wherein the scaffold is configured to bind to the target. Energy can be applied to the sample, wherein the applied energy is sufficient to transform at least some of the sample into a plasma. Electromagnetic radiation emitted by the plasma can be detected to provide an optical-spectrum signal of the sample.

1 . A method for characterizing a target within a sample, the method comprising:
 applying to the sample a recognition construct comprising a metal and a scaffold, wherein the scaffold is configured to bind to the target;   retaining the sample on a substrate;   applying energy to the sample, wherein the applied energy is sufficient to transform at least some of the sample into a plasma; and   detecting electromagnetic radiation emitted by the plasma to provide an optical-spectrum signal of the sample;   generating a normalized optical-spectrum signal by normalizing the optical-spectrum signal of the sample with respect to an optical-spectrum signal of a material of the substrate; and   characterizing the target in the sample based at least in part on the normalized optical-spectrum signal.   
     
     
         2 . The method according to  claim 1 , wherein the applying energy comprises heating at least part of the sample. 
     
     
         3 . The method according to  claim 1 , wherein the applying energy comprises irradiating at least part of the sample using a laser. 
     
     
         4 . The method according to  claim 1 , wherein the applying energy comprises applying a spark to at least part of the sample. 
     
     
         5 . The method according to  claim 1 , wherein characterizing the target in the sample comprises:
 determining presence of the metal based at least in part on the normalized optical-spectrum signal by performing at least spectral unmixing or constrained energy minimization (CEM).   
     
     
         6 . The method according to  claim 1 , further comprising:
 preparing the recognition construct by bonding the metal to the scaffold, wherein the scaffold comprises a biological scaffold and the metal comprises a metal atom or ion.   
     
     
         7 . The method according to  claim 1 , wherein the target includes a microbe and the scaffold comprises an antibody against epitopes present on a surface of the microbe. 
     
     
         8 . The method according to  claim 1 , wherein the target includes a biological toxin and the scaffold comprises an antibody against the biological toxin. 
     
     
         9 . The method according to  claim 1 , wherein:
 the scaffold is configured to couple with the target,   the metal comprises a metal atom or ion, and   the recognition construct further comprises a polymer that is coupled to the scaffold, linked to the metal atom or ion, and comprises a metal-chelating ligand.   
     
     
         10 . The method according to  claim 9 , wherein the metal-chelating ligand comprises diethylenetriaminepenta-acetic acid (DTPA), 
     
     
         11 . The method according to  claim 1 , wherein characterizing the target in the sample comprises:
 determining presence of the metal by applying the normalized optical-spectrum signal of the sample to a multi-class classifier selected from the group consisting of a support vector machine, a kernel estimator, a nearest-neighbor classifier, a decision tree, a decision forest, a neural network, or a deep neural network.   
     
     
         12 . The method according to  claim 1 , wherein the scaffold comprises at least one of: adNectin, iMab, anticalin, designed ankyrin repeat protein (DARPin), affilin, tetranectin, or avimer. 
     
     
         13 . The method according to  claim 1 , wherein the first metal atom or ion linked to the metal-chelating ligand comprises a lanthanide. 
     
     
         14 . A method comprising:
 applying to a sample a recognition construct comprising a metal and a scaffold, wherein the scaffold is configured to bind to the target;   retaining the sample on a substrate;   applying energy to the sample, wherein the applied energy is sufficient to transform at least some of the sample into a plasma; and   detecting electromagnetic radiation emitted by the plasma to provide an optical-spectrum signal of the sample;   generating a normalized optical-spectrum signal by normalizing the optical-spectrum signal of the sample with respect to an optical-spectrum signal of a material of the substrate; and   determining presence of the target in the sample based at least in part on the normalized optical-spectrum signal.   
     
     
         15 . The method according to  claim 14 , wherein the applying energy comprises at least one of:
 heating at least part of the sample;   irradiating at least part of the sample using a laser; or   applying a spark to at least part of the sample.   
     
     
         16 . The method according to  claim 14 , wherein determining the presence of the target in the sample comprises performing at least one of spectral unmixing or constrained energy minimization (CEM) on the normalized optical-spectrum signal. 
     
     
         17 . The method according to  claim 14 , wherein determining the presence of the metal comprises applying the normalized optical-spectrum signal of to a multi-class classifier comprising at least one of a support vector machine, a kernel estimator, a nearest-neighbor classifier, a decision tree, a decision forest, a neural network, or a deep neural network. 
     
     
         18 . The method according to  claim 14 , wherein:
 the scaffold is configured to couple with the target,   the metal comprises a metal atom or ion, and   the recognition construct further comprises a polymer that is coupled to the scaffold, linked to the metal atom or ion, and comprises a metal-chelating ligand.   
     
     
         19 . A method for characterizing a target within a sample, the method comprising:
 causing the target to bind with a recognition construct, the recognition construct comprising a scaffold configured to bind with the target; a polymer coupled to the scaffold and comprising a metal-chelating ligand; and a metal atom or ion linked to the metal chelating ligand, the sample comprising the target bound with the recognition construct;   causing the target within the sample to be bound to a capture antibody that is coupled to a silicon substrate;   in response to causing the target to be bound to the capture antibody, applying energy to the sample, wherein the applied energy is sufficient to transform at least some of the sample into a plasma; and   detecting electromagnetic radiation emitted by the plasma to provide an optical-spectrum signal of the sample;   generating a normalized optical-spectrum signal by normalizing the optical-spectrum signal of the sample with respect to an optical-spectrum signal of silicon; and   identifying presence of the target in the sample by detecting presence of the metal atom or ion based at least in part on the normalized optical-spectrum signal.   
     
     
         20 . The method of  claim 19 , wherein:
 the scaffold comprises at least one of adNectin, iMab, anticalin, designed ankyrin repeat protein (DARPin), affilin, tetranectin, or avimer;   the metal-chelating ligand comprises diethylenetriaminepenta-acetic acid (DTPA); and   the first metal atom or ion linked to the metal-chelating ligand comprises a lanthanide.