Systems and methods for label-free detection of analytes

Abstract

Disclosed are methods of detecting an analyte of interest comprising introducing a sample comprising an analyte of interest to an antibody or antibody fragment; incubating the sample and antibody or antibody fragment under conditions sufficient to allow binding of the analyte of interest to the antibody or antibody fragment; and detecting the binding of the analyte of interest to the antibody or antibody fragment using a label-free second harmonic detection system. Also disclosed are methods of screening and diagnosing using antibodies or antibody fragments and a label-free second harmonic detection system.

We claim: 
     
         1 . A method of screening for analytes that bind an antibody or antibody fragment comprising
 a) introducing an analyte to an antibody or antibody fragment; and   b) detecting the presence of the analyte bound to the antibody or antibody fragment using a label-free second harmonic detection system,   wherein the presence of the analyte bound to the antibody or antibody fragment indicates the analyte binds the antibody or antibody fragment.   
     
     
         2 . The method of  claim 1 , wherein the antibody or antibody fragment is immobilized on a support. 
     
     
         3 . The method of  claim 1 , wherein the antibody or antibody fragment is known to bind the analyte of interest. 
     
     
         4 . The method of  claim 1 , wherein the analyte is a protein, nucleic acid, small molecule, or fragment thereof. 
     
     
         5 . The method of  claim 1 , wherein detecting the presence of the analyte bound to the antibody or antibody fragment using the label-free second harmonic detection system comprises using second harmonic imaging (SHI) to detect the binding of the analyte to the antibody or antibody fragment. 
     
     
         6 . The method of  claim 5 , wherein detecting the presence of the analyte bound to the antibody or antibody fragment using the label-free second harmonic detection system further comprises determining binding properties of the analyte of interest using second-harmonic correlation spectroscopy.