Systems and Methods for Biological Analysis

Abstract

A system for performing biological reactions is provided. The system includes a chip including a substrate and a plurality of reaction sites. The plurality of reaction sites are each configured to include a liquid sample of at most one nanoliter. Further, the system includes a control system configured to initiate biological reactions within the liquid samples. The system further includes a detection system configured to detect biological reactions on the chip. According to various embodiments, the chip includes at least 20000 reaction sites. In other embodiments, the chip includes at least 30000 reaction sites.

What is claimed is: 
     
         1 . A system for performing biological reactions, the system comprising:
 a chip including a plurality of reaction sites, wherein the plurality of reaction sites are each configured to include a liquid sample of at most one nanoliter;   a control system configured to initiate biological reactions in the liquid samples; and   a detection system configured to detect biological reactions on the chip.   
     
     
         2 . The system of  claim 1 , wherein the chip includes at least 20000 reaction sites. 
     
     
         3 . The system of  claim 1 , wherein the chip includes at least 30000 reaction sites. 
     
     
         4 . The system of  claim 1 , wherein each reaction site of the plurality of reaction sites is a through-hole. 
     
     
         5 . The system of  claim 1 , wherein each reaction site of the plurality of reaction sites is a well. 
     
     
         6 . The system of  claim 1 , wherein the control system is configured to perform polymerase chain reaction (PCR). 
     
     
         7 . The system of  claim 6 , wherein the control system is configured to perform digital PCR. 
     
     
         8 . The system of  claim 1 , wherein the detection system includes an optical system, wherein the optical system includes an excitation source and an optical sensor configured to detect fluorescent signals emitted from a plurality of liquid samples within the plurality of reaction sites. 
     
     
         9 . The system of  claim 1 , wherein a surface of the reaction sites are hydrophilic. 
     
     
         10 . The system of  claim 9 , wherein a surface of the substrate is hydrophilic. 
     
     
         11 . The system of  claim 1 , wherein the chip is enclosed in a carrier. 
     
     
         12 . The system of  claim 11 , wherein the chip is immersed in an encapsulating medium within the carrier. 
     
     
         13 . The system of  claim 12 , wherein the encapsulating medium is polydimethylsiloxane (PDMS), wherein the PDMS fully cured and not completely cross-linked. 
     
     
         14 . The system of  claim 11 , wherein the carrier includes a funnel guide configured to facilitate loading a liquid sample into at least some of the plurality of sample areas. 
     
     
         15 . The system of  claim 12 , wherein the encapsulating medium is configured to reduce evaporation of the liquid sample. 
     
     
         16 . The system of  claim 12 , wherein the encapsulating medium is preloaded in the carrier before the chip is inserted. 
     
     
         17 . The system of  claim 1 , wherein the chip has an area of 10 mm by 10 mm. 
     
     
         18 . The system of  claim 1 , wherein the plurality of reaction sites include a range of volumes to increase dynamic range. 
     
     
         19 . The system of  claim 1 , wherein the chip and the plurality of reaction sites are configured to load the liquid sample to the plurality of reaction sites. 
     
     
         20 . The system of  claim 19 , wherein the plurality of reaction sites are configured to be loaded with more than one sample. 
     
     
         21 . The system of  claim 1 , wherein the optical system has a focal length of 15 mm. 
     
     
         22 . The system of  claim 19 , wherein a first portion of the plurality of reaction sites are loaded with the liquid sample at a first dilution and a second portion of the plurality of reaction sites are loaded with the liquid sample at a second dilution to increase dynamic range. 
     
     
         23 . The system of  claim 10 , wherein the surface of the reaction site and the surface of the substrate are coated with a material. 
     
     
         24 . The system of  claim 23 , wherein the material is hexamethyldisilazane (HMDS). 
     
     
         25 . The system of  claim 23 , wherein the surface of the reaction site and the surface of the substrate are coated by vapor deposition. 
     
     
         26 . The system of  claim 23 , wherein the liquid sample has a contact angle of 70-100 degrees with the material. 
     
     
         27 . The system of  claim 23 , wherein the liquid sample is loaded to the reaction sites by capillary action. 
     
     
         28 . A method for performing biological reactions, the method comprising:
 loading a chip including a substrate and a plurality of reaction sites with a liquid sample, wherein the plurality of reaction sites are each configured to include a volume of the liquid sample of at most one nanoliter;   initiating biological reactions in the plurality of reaction sites; and   detecting, with an optical system, a plurality of biological reactions on the chip.   
     
     
         29 . The method of  claim 28 , wherein the chip includes at least 20000 reaction sites. 
     
     
         30 . The method of  claim 28 , wherein the chip includes at least 30000 reaction sites. 
     
     
         31 . The method of  claim 28 , wherein each reaction site of the plurality of reaction sites is a through-hole. 
     
     
         32 . The method of  claim 28 , wherein each reaction site of the plurality of reaction sites is a well.