Method for amplification-free nucleic acid detection on optofluidic chips

Abstract

An optofluidic platform is constructed so as to comprise a planar, liquid-core integrated optical waveguides for specific detection of nucleic acids. Most preferably, the optical waveguides comprises antiresonant reflecting optical waveguide (ARROWs). A liquid solution can be prepared and introduced into the optofluidic platform for optical excitation. The resulting optical signal can be collected at the edges of the optofluidic platform and can be analyzed to determine the existence of a single and/or a specific nucleic acid.

We claim: 
     
         1 . A system for detecting single nucleic acid particles in a liquid solution, comprising:
 a planar optofluidic platform;   a light source arranged to optically excite a liquid solution introduced into the planar optofluidic platform, whereby a fluorescence signal is generated; and   a light sensor arranged to detect the fluorescence signal and produce an electric signal for determining the presence of a specific nucleic acid.   
     
     
         2 . The system of  claim 1 , further comprising means for determining that the generated signal comprises fluorescence bursts. 
     
     
         3 . The system of  claim 1 , wherein the planar optofluidic platform comprises planar, liquid-core integrated optical waveguides. 
     
     
         4 . The system of  claim 1 , wherein the planar optofluidic platform comprises hollow-core antiresonant reflecting optical waveguides (ARROWs), solid-core ARROWs connected to different points of the hollow-core ARROWs, a first port for introducing liquid solutions in the hollow-core ARROWs, a second port for introducing excitation light to the hollow-core ARROWs, and a third port for collecting the generated fluorescence signal. 
     
     
         5 . The system of  claim 4 , wherein the first port comprises a fluidic reservoir contained in the planar optofluidic platform. 
     
     
         6 . The system of  claim 4 , wherein the third port is configured for collecting at edges of the planar optofluidic platform generated light perpendicular to the planar optofluidic platform. 
     
     
         7 . The system of  claim 1 , wherein the light sensor comprises a photodetector or avalanche photodiode. 
     
     
         8 . An optofluidic system for amplification-free detection of a specific nucleic acid sequence in a liquid solution, comprising:
 a planar hollow-core antiresonant reflecting waveguide (ARROW);   a planar solid-core ARROW intersecting the hollow-core ARROW at a sub-picoliter optical excitation region;   first and second fluidic reservoirs at ends of the hollow-core ARROW configured for introducing a liquid solution into the hollow-core ARROW, the liquid solution comprising a specific nucleic acid sequence and a nucleic acid probe labeled with fluorophores, wherein the nucleic acid probe specifically hybridizes with the specific nucleic acid sequence in the liquid solution;   a light source configured for providing an excitation light to the optical excitation region; and   a light sensor configured for collecting a fluorescent signal generated in the optical excitation region, wherein the fluorescent signal is indicative of the presence of the specific nucleic acid sequence.   
     
     
         9 . The system of  claim 8 , further comprising means for inducing electrokinetic particle movement to the liquid solution in the one of the hollow-core ARROWs. 
     
     
         10 . The system of  claim 8 , wherein the solid-core ARROW is configured to provide a path for the excitation light to enter the hollow-core ARROW at the optical excitation region, and a path for collecting a fluorescent signal perpendicularly to the plane of the planar optofluidic system and for guiding the fluorescent signal to edges of the planar optofluidic system for detection. 
     
     
         11 . The system of  claim 8 , further comprising a second hollow-core ARROW, a port for introducing a pure buffer solution free of nucleic acids into the second hollow-core ARROW, and second solid-core ARROW intersecting the second hollow-core ARROW, wherein a fluorescent signal generated from the liquid solution in the optical excitation region can be compared to a signal from the pure buffer solution. 
     
     
         12 . The system of  claim 8 , wherein the light source comprises a laser. 
     
     
         13 . The system of  claim 8 , wherein the light sensor comprises a photodetector or avalanche photodiode. 
     
     
         14 . The system of  claim 8 , further comprising means for creating a fluorescence correlation spectrum using the fluorescent signal. 
     
     
         15 . The system of  claim 8 , further comprising means for creating a plot of the fluorescent signal.