Universal Sample Preparation System And Use In An Integrated Analysis System

Abstract

The invention provides for devices and methods for interfacing microchips to cartridges and pneumatic manifolds. The cartridges, microchips, and pneumatic manifolds can be integrated with downstream preparation devices, such as thermal regulating devices and separation and analysis devices.

1 .- 124 . (canceled) 
     
     
         125 . An integrated biochip system comprising:
 (a) a biochip comprising a plurality microfluidic systems, wherein each microfluidic system comprises a first reaction chamber in microfluidic communication with a separation chamber, wherein the first reaction chamber is adapted for:
 (i) nucleic acid extraction; 
 (ii) nucleic acid purification; 
 (iii) pre-nucleic acid amplification cleanup; 
 (iv) nucleic acid amplification; 
 (v) post-nucleic acid amplification cleanup; 
 (vi) pre-nucleic acid sequencing cleanup; 
 (vii) nucleic acid sequencing; 
 (viii) post-nucleic acid sequencing cleanup; 
 (ix) reverse transcription; 
 (x) pre-reverse transcription cleanup; 
 (xi) post-reverse transcription cleanup; 
 (xii) nucleic acid ligation; 
 (xiii) nucleic acid hybridization; or 
 (xiv) quantification; 
   and the separation chamber comprises a detection position; and   (b) a separation and detection system comprising,
 (i) a separation element for simultaneously separating a plurality of target analytes in the separation chamber; 
 (ii) one or more light sources positioned to illuminate the detection positions on the biochip; 
 (iii) a mirror to scan said one or more light sources sequentially between said detection positions; 
 (iv) one or a plurality of first optical elements positioned for collecting and directing light emanating from the detection positions; and 
 (v) a light detector positioned to accept light directed from the one or plurality of first optical elements, 
   wherein the light detector comprises a wavelength dispersive element to disperse the light from the one or plurality of first optical elements according to light wavelength into at least 6 wavelength components and, the wavelength dispersive element is positioned to provide at least a portion of the dispersed at least 6 wavelength components to at least 6 detection elements, wherein each of the detection elements is in communication with a first control element for simultaneously collecting detection information from each of the detection elements; and   wherein said light detector detects fluorescence from at least 6 dyes labeled to one or more biological molecules, each dye having a unique peak wavelength.   
     
     
         126 . The integrated biochip system of  claim 125 , wherein the first reaction chamber is adapted for nucleic acid extraction. 
     
     
         127 . The integrated biochip system of  claim 125 , wherein the first reaction chamber is adapted for nucleic acid purification. 
     
     
         128 . The integrated biochip system of  claim 125 , wherein the first reaction chamber is adapted for nucleic acid amplification. 
     
     
         129 . The integrated biochip system of  claim 125 , wherein the first reaction chamber is adapted for cleanup. 
     
     
         130 . The integrated biochip system of  claim 125 , wherein the first reaction chamber is adapted for nucleic acid sequencing. 
     
     
         131 . The integrated biochip system of  claim 125 , wherein the first reaction chamber is adapted for reverse transcription. 
     
     
         132 . The integrated biochip system of  claim 125 , wherein the first reaction chamber is adapted for nucleic acid ligation. 
     
     
         133 . The integrated biochip system of  claim 125 , wherein the first reaction chamber is adapted for nucleic acid hybridization. 
     
     
         134 . The integrated biochip system of  claim 125 , wherein the first reaction chamber is adapted for quantification. 
     
     
         135 . An integrated biochip system comprising:
 (a) a biochip comprising a plurality microfluidic systems, wherein each microfluidic system comprises a first reaction chamber in microfluidic communication with a separation chamber, wherein the first reaction chamber is adapted for
 (i) nucleic acid extraction; 
 (ii) nucleic acid purification; 
 (iii) pre-nucleic acid amplification cleanup; 
 (iv) nucleic acid amplification; 
 (v) post-nucleic acid amplification cleanup; 
 (vi) pre-nucleic acid sequencing cleanup; 
 (vii) nucleic acid sequencing; 
 (viii) post-nucleic acid sequencing cleanup; 
 (ix) reverse transcription; 
 (x) pre-reverse transcription cleanup; 
 (xi) post-reverse transcription cleanup; 
 (xii) nucleic acid ligation; 
 (xiii) nucleic acid hybridization; or 
 (xiv) quantification; and the separation chamber comprises a detection position; and 
   (b) a separation and detection system comprising,
 (i) a separation element for simultaneously separating a plurality of biological molecules comprising DNA sequences, in the separation chamber; 
 (ii) one or more light sources positioned to illuminate the detection positions on the biochip; 
 (iii) a mirror to scan said one or more light sources sequentially between said detection positions; 
 (iv) one or a plurality of first optical elements positioned for collecting and directing light emanating from the detection positions; and 
 (v) a light detector positioned to accept light directed from the one or plurality of first optical elements, 
 wherein the light detector comprises a wavelength dispersive element to disperse the light from the one or plurality of first optical elements according to light wavelength into at least 6 wavelength components, and the wavelength dispersive element positioned to provide at least a portion of the dispersed at least 6 wavelength components to at least 6 detection elements, 
 wherein each of the detection elements is in communication with a first control element for simultaneously collecting detection information from each of the detection elements; and 
 wherein said light detector detects fluorescence from at least 8 dyes labeled to one or more DNA sequences, each dye having a unique peak wavelength, said dyes being members of at least two 4-dye containing subsets, such that said dye sets are capable of detecting at least two DNA sequences in a single channel, wherein the number of dyes is a multiple of four, and the number of DNA sequences to be detected is equal to one quarter of the multiple, such that each of the different dyes is present in only one subset. 
   
     
     
         136 . A system, comprising:
 (a) a microchip comprising a plurality microfluidic systems, wherein each microfluidic system comprises a first reaction chamber in microfluidic communication with a separation chamber, wherein the first reaction chamber is adapted for:
 (i) nucleic acid extraction; 
 (ii) nucleic acid purification; 
 (iii) pre-nucleic acid amplification cleanup; 
 (iv) nucleic acid amplification; 
 (v) post-nucleic acid amplification cleanup; 
 (vi) pre-nucleic acid sequencing cleanup; 
 (vii) nucleic acid sequencing; 
 (viii) post-nucleic acid sequencing cleanup; 
 (ix) reverse transcription; 
 (x) pre-reverse transcription cleanup; 
 (xi) post-reverse transcription cleanup; 
 (xii) nucleic acid ligation; 
 (xiii) nucleic acid hybridization; or 
 (xiv) quantification; 
   and the separation chamber comprises a detection position; and   (b) a separation and detection system comprising:
 (i) a separation element for simultaneously separating a plurality of target analytes in the separation chamber; 
 (ii) an optical assembly positioned to illuminate the detection positions on the microchip, and for collecting and directing light emanating from the detection positions; and 
 (iv) a light detector positioned to accept light directed from the optical assembly, 
   wherein said light detector is in communication with a processor for simultaneously collecting detection information from said light detector; and   wherein said light detector detects fluorescence from a plurality of dyes labeled to one or more biological molecules, each dye having a unique peak wavelength.   
     
     
         137 . The system of  claim 136 , wherein the first reaction chamber is adapted for nucleic acid extraction. 
     
     
         138 . The system of  claim 136 , wherein the first reaction chamber is adapted for nucleic acid purification. 
     
     
         139 . The system of  claim 136 , wherein the first reaction chamber is adapted for nucleic acid amplification. 
     
     
         140 . The system of  claim 136 , wherein the first reaction chamber is adapted for cleanup. 
     
     
         141 . The system of  claim 136 , wherein the first reaction chamber is adapted for nucleic acid sequencing. 
     
     
         142 . The system of  claim 136 , wherein the first reaction chamber is adapted for reverse transcription. 
     
     
         143 . The system of  claim 136 , wherein the first reaction chamber is adapted for nucleic acid ligation. 
     
     
         144 . The system of  claim 136 , wherein the first reaction chamber is adapted for nucleic acid hybridization. 
     
     
         145 . The system of  claim 136 , wherein the first reaction chamber is adapted for quantification. 
     
     
         146 . A system, comprising:
 (a) a microchip comprising a plurality microfluidic systems, wherein each microfluidic system comprises a first reaction chamber in microfluidic communication with a separation chamber, wherein the first reaction chamber is adapted for
 (i) nucleic acid extraction; 
 (ii) nucleic acid purification; 
 (iii) pre-nucleic acid amplification cleanup; 
 (iv) nucleic acid amplification; 
 (v) post-nucleic acid amplification cleanup; 
 (vi) pre-nucleic acid sequencing cleanup; 
 (vii) nucleic acid sequencing; 
 (viii) post-nucleic acid sequencing cleanup; 
 (ix) reverse transcription; 
 (x) pre-reverse transcription cleanup; 
 (xi) post-reverse transcription cleanup; 
 (xii) nucleic acid ligation; 
 (xiii) nucleic acid hybridization; or 
 (xiv) quantification; and the separation chamber comprises a detection position; and 
   (b) a separation and detection system comprising:
 (i) a separation element for simultaneously separating a plurality of biological molecules comprising DNA sequences, in the separation chamber; 
 (ii) an optical assembly positioned to illuminate the detection positions on the microchip, and for collecting and directing light emanating from the detection positions; and 
 (iv) a light detector positioned to accept light directed from the optical assembly, 
 wherein the light detector comprises a wavelength dispersive element to disperse the light from the one or plurality of first optical elements according to light wavelength into at least 6 wavelength components, and the wavelength dispersive element positioned to provide at least a portion of the dispersed at least 6 wavelength components to at least 6 detection elements, 
 wherein said light detector is in communication with a processor for simultaneously collecting detection information from said light detector; and 
 wherein said light detector detects fluorescence from a plurality of dyes labeled to one or more DNA sequences, each dye having a unique peak wavelength, said dyes being members of at least two 4-dye containing subsets, such that said dye sets are capable of detecting at least two DNA sequences in a single channel, wherein the number of dyes is a multiple of four, and the number of DNA sequences to be detected is equal to one quarter of the multiple, such that each of the different dyes is present in only one subset.