Methods and systems for detecting biomolecular binding using terahertz radiation

Abstract

Provided herein are methods and systems for detecting biomolecular binding events using gigahertz or terahertz radiation. The methods and systems use low-energy spectroscopy to detect biomolecular binding events between molecules in an aqueous solution. The detected biomolecular binding events include, for example, nucleic acid hybridizations, antibody/antigen binding, and receptor/ligand binding.

1 . A system for detecting a biomolecular binding event, the system comprising: 
 a) a sample containing a first molecule and a second molecule, wherein the first molecule is suspected of binding the second molecule;    b) a terahertz or gigahertz radiation source positioned to aim an input radiation toward the sample; and    c) a detector for receiving an exit radiation reflecting from the sample.    
     
     
         2 . The system of  claim 1 , wherein the system further comprises a substrate that is transparent to the terahertz radiation, wherein the first molecule is immobilized on the substrate.  
     
     
         3 . The system of  claim 2 , further comprising a reaction chamber adjacent to the substrate.  
     
     
         4 . The system of  claim 3 , wherein a solution in the receptacle comprises the second molecule.  
     
     
         5 . The system of  claim 4 , wherein the solution comprises water.  
     
     
         6 . The system of  claim 2 , wherein the substrate is a surface of a waveguide.  
     
     
         7 . The system of  claim 1 , further comprising no more than one diffraction grating positioned between the sample and the detector.  
     
     
         8 . The method of  claim 1 , wherein the first molecule is a nucleic acid.  
     
     
         9 . The method of  claim 1 , wherein the second molecule is a nucleic acid.  
     
     
         10 . The method of  claim 1 , wherein the second molecule is a protein.  
     
     
         11 . The method of  claim 1 , wherein the first molecule is a receptor and the second molecule is a ligand.  
     
     
         12 . The method of  claim 1 , wherein the first molecule is a protein and the second molecule is a protein.  
     
     
         13 . An apparatus for detecting a biomolecular binding event in a sample containing a first molecule and a second molecule, wherein the first molecule is suspected of binding the second molecule, comprising: 
 a terahertz radiation source positioned to aim an input radiation toward the sample; and    a detector positioned to receive an exit radiation reflecting from the sample.    
     
     
         14 . The apparatus of  claim 13 , further comprising an information processing and control system in communication with the detector.  
     
     
         15 . The apparatus of  claim 14 , wherein the information processing and control system is capable of analyzing the data received from the detector.  
     
     
         16 . The apparatus of  claim 13 , further comprising a spectrum analyzer.  
     
     
         17 . The apparatus of  claim 13 , further comprising sample holder.  
     
     
         18 . The apparatus of  claim 17 , wherein the sample holder includes a substrate that is transparent to the terahertz radiation, wherein the first molecule is immobilized on the substrate.  
     
     
         19 . The apparatus of  claim 18 , further comprising a reaction chamber adjacent to the substrate, wherein a solution in the reaction chamber includes the second molecule.  
     
     
         20 . The apparatus of  claim 18 , wherein the substrate include a waveguide with an input portion and an output portion, wherein the first molecule is immobilized on the waveguide.  
     
     
         21 . The apparatus of  claim 20 , wherein the terahertz radiation source is positioned to aim the input radiation toward the input portion of the waveguide and the detector positioned to receive the exit radiation from the output portion of the waveguide.  
     
     
         22 . The apparatus of  claim 13 , further comprising a filter to select a predetermined bandwidth radiation emitted by the terahertz radiation source.  
     
     
         23 . The apparatus of  claim 13 , wherein the terahertz radiation source has a bandwidth between 0.001 and 1000 THz.  
     
     
         24 . The apparatus of  claim 13 , wherein the first molecule is a nucleic acid.  
     
     
         25 . The apparatus of  claim 13 , wherein the second molecule is a nucleic acid.  
     
     
         26 . The apparatus of  claim 13 , wherein the second molecule is a protein.  
     
     
         27 . The apparatus of  claim 13 , wherein the first molecule is a receptor and the second molecule is a ligand.  
     
     
         28 . The apparatus of  claim 13 , wherein the first molecule is a protein and the second molecule is a protein.  
     
     
         29 . A micro-electro-mechanical system (MEMS) for detecting a biomolecular binding event in a sample containing a first molecule and a second molecule, wherein the first molecule is suspected of binding the second molecule, comprising: 
 one or more fluid compartments for the sample;    a radiation source positioned to aim an input radiation toward the sample; and    a detector positioned to receive an exit radiation reflecting from the sample.    
     
     
         30 . The apparatus of  claim 29 , further comprising an information processing and control system in communication with the detector.  
     
     
         31 . The apparatus of  claim 30 , wherein the fluid compartment includes a substrate that is transparent to the terahertz radiation, wherein the first molecule is immobilized on the substrate.  
     
     
         32 . The apparatus of  claim 31 , wherein the substrate include a waveguide with an input portion and an output portion, wherein the first molecule is immobilized on the waveguide.  
     
     
         33 . The apparatus of  claim 32 , wherein the radiation source is positioned to aim the input radiation toward the input portion of the waveguide and the detector positioned to receive the exit radiation from the output portion of the waveguide.  
     
     
         34 . The apparatus of  claim 29 , further comprising a filter to select a predetermined bandwidth radiation emitted by the radiation source.