Dual-mode microfluidic genetics testing platforms and methods of dual-mode genetics testing using same

Abstract

Dual mode genetics testing systems are devised about a single element testing platform. A microfluidic network and system of interconnected receiving cells and reaction vessels supports at the same time genotyping and copy number analysis where the platform may be subject to a common thermal cycle schedule to cause the proper reactions (DNA replication) necessary in both test types. Further, the microfluidic platform which includes reaction vessels for genotyping which are spatially removed from reaction vessels for copy number analysis, is coupled to optical scanner and detection systems specifically arranged to apply test specific detection routines on each of these distinct regions or portions of the dual mode test platform.

What is claimed is: 
     
         1 . Dual mode genetic testing platforms comprising:
 a microfluidic platform;   a polymerase chain reaction thermal cycler; and   a multi-channel optical detector,   said microfluidic platform is comprised of two modules including:
 a copy number analysis module; and 
 a genotyping module, 
 said copy number analysis module is spatially removed and separate from said genotyping module and each being optically coupled to a separate channel of the multi-channel optical detector, 
 said copy number analysis module and said genotyping module are each comprised of a plurality of reaction vessels, and 
 said copy number analysis module and said genotyping module are each thermally coupled to said thermal cycler. 
   
     
     
         2 . Dual mode genetic testing platforms of  claim 1 , said multi-channel optical detector having a CCD device with a first channel coupled to reaction vessels of said copy number analysis module and a second channel coupled to reaction vessels said genotyping module, the reaction vessels of the genotyping module are spatially removed from reaction vessels of the copy number analysis module whereby separate optical signals may be captured with respect to each module. 
     
     
         3 . Dual mode genetic testing platforms of  claim 2 , said first channel coupled to said genotyping module being further comprised of driver electronics operable for capturing an optical signal at a discrete moment in time; and
 a second channel coupled to said copy number analysis module being further comprised of driver electronics operable for capturing a plurality of discrete optical signals over the course of an extended period of time   
     
     
         4 . Dual mode genetic testing platforms of  claim 3 , said first channel is further arranged with driver electronics operable for capturing optical signals of a plurality of wavelengths. 
     
     
         5 . Dual mode genetic testing platforms of  claim 4 , each wavelength corresponds to a different version of a single nucleotide polymorphism. 
     
     
         6 . Dual mode genetic testing platforms of  claim 3 , said second channel is further arranged with driver electronics which enable the optical detector to detect return optical signal of intensities which range over at least two orders of magnitude. 
     
     
         7 . Dual mode genetic testing platforms of  claim 1 , said genetic testing platform is further comprised of reagent chemistry characterized as ‘TaqMan’ type PCR reagents. 
     
     
         8 . Dual mode genetic testing platforms of  claim 7 , said TaqMan chemistry is provided in two compositions, one TaqMan composition for use with the genotyping module and another TaqMan composition for use with the copy number analysis module. 
     
     
         9 . Dual mode genetic testing platforms of  claim 8 , said TaqMan chemistry composition associated with the copy number analysis module is further comprised of a contrast agent. 
     
     
         10 . Dual mode genetic testing platforms of  claim 6 , said copy number analysis module is further comprised of a known reference allele arrange to react with TaqMan chemistry to produce an optical signal by which a comparison may be made with respect to alleles under test. 
     
     
         11 . Dual mode genetic testing platforms of  claim 7 , said TaqMan chemistry includes genetic probes arranged with a plurality of color florochromes optical reporters—one said optical reporter each for each SNP version. 
     
     
         12 . Dual mode genetic testing platforms of  claim 1 , further comprising a DNA sample whereby at least one receiving cell of the genotyping module and at least one receiving cell of the copy number analysis module each receive a portion of the identical DNA sample. 
     
     
         13 . Dual mode genetic testing methods comprising the steps:
 i) providing a plurality of receiving cells in two distinct test modules with TaqMan reagent chemistry, said two distinct test modules including a genotyping module and a copy number analysis module;   ii) providing at least one DNA sample in a plurality of receiving cells of two distinct test modules including a genotyping module and a copy number analysis module;   iii) mixing provided TaqMan reagents with at least one sample DNA;   iv) executing a repeated cycle to induce replication of DNA and multiply copies whereby the cycle includes:
 a) heating genetic matter in a reaction vessel to cause denaturing of a DNA sample double helix; 
 b) cooling genetic matter in the reaction vessel to cause annealing and replication of DNA sample; 
 c) illuminating the copy number analysis module with high energy light to stimulate fluorescence in the reaction cells thereof; 
 d) capturing an optical return signal from the copy number analysis module; and 
 e) determining whether the last executed cycle is a final cycle of a prescribed thermal cycle schedule; 
   v) illuminating the genotyping module with high energy light to stimulate fluorescence in the reaction cells thereof; and   vi) capturing a spatially distributed optical signal from the genotyping module.   
     
     
         14 . Dual mode genetic testing methods of  claim 13 , said “providing TaqMan reagent chemistry ” step is further characterized as loading receiving cells of a copy number analysis module with TaqMan chemistry; and loading receiving cells of a genotyping module with another TaqMan chemistry. 
     
     
         15 . Dual mode genetic testing methods of  claim 14 , said “loading receiving cells of a copy number analysis module” is further characterized as providing a TaqMan composition with an additive to enhance contrast. 
     
     
         16 . Dual mode genetic testing methods of  claim 13 , said “providing at least one DNA sample ” is further characterized as providing a reference oligo in at least one receiving cell of the copy number analysis module. 
     
     
         17 . Dual mode genetic testing methods of  claim 13 , said “capturing an optical return signal from the copy number analysis module” is further characterized as capturing a plurality of signals over the course of a thermal cycle schedule to form a plot of return signal intensity v. thermal cycles applied from which a copy number determination may be based. 
     
     
         18 . Dual mode genetic testing methods of  claim 13 , said “capturing an optical return signal from the genotype module” is further characterized as capturing and thresholding an optical signal at the end of a thermal cycle schedule from which a genotype determination may be based. 
     
     
         19 . Dual mode genetic testing methods of  claim 17 , said capturing an optical signal from the genotyping module is characterized as capturing a bi-color signal whereby a determination as to heterozygote, homozygote major and minor may be made. 
     
     
         20 . Dual mode genetic testing methods of  claim 13 , said “providing at least one DNA sample” step is further characterized as placing DNA from a single organism in at least one receiving cell of the genotyping module and at least one receiving cell of the copy number analysis module.