Integrated nucleic acid diagnostic device

Abstract

The present invention provides a miniaturized integrated nucleic acid diagnostic device and system. The device of the invention is generally capable of performing one or more sample acquisition and preparation operations, in combination with one or more sample analysis operations. For example, the device can integrate several or all of the operations involved in sample acquisition and storage, sample preparation and sample analysis, within a single integrated unit. The device is useful in a variety of applications, and most notably, nucleic acid based diagnostic applications and de novo sequencing applications.

1 - 65 . (canceled)  
     
     
         66 . A miniature fluidic system, comprising: 
 a body having at least two chambers disposed therein, at least one of said at least two chambers being a cell lysis chamber, for lysing cells in said fluid sample, said cell lysis chamber comprising a cell lysis system;    a sample inlet, fluidly connected to at least one of said at least two chambers, for introducing a fluid sample into said at least one chamber; and    a fluid transport system for moving a fluid sample from at least a first of said at least two chambers to at least a second chamber of said at least two chambers.    
     
     
         67 . The system of  claim 66 , wherein said cell lysis system comprises a series of microstructures fabricated on an internal surface of said lysis chamber, whereby flowing said fluid sample over said microstructures results in lysis of cells in said fluid sample.  
     
     
         68 . The system of  claim 67 , wherein said cell lysis system further comprises a piezoelectric element disposed adjacent said cell lysis chamber for flowing said fluid sample over said microstructures.  
     
     
         69 . The system of  claim 67 , wherein said cell lysis chamber comprises an electrolytic pH control system, for altering a pH in said cell lysis chamber.  
     
     
         70 . A miniature fluidic system, comprising: 
 a body having at least two chambers disposed therein, at least one of said at least two chambers being a nucleic acid purification chamber, for separating nucleic acids in said fluid sample from other contaminants in said fluid sample;    a sample inlet, fluidly connected to at least one of said at least two chambers, for introducing a fluid sample into said at least one chamber; and    a fluid transport system for moving said separated nucleic acids from said nucleic acid chamber to said at least a second chamber of said at least two chambers.    
     
     
         71 . The system of  claim 70 , wherein said nucleic acid purification system comprises a separation matrix which selectively binds nucleic acids in said fluid sample, but not said other contaminants.  
     
     
         72 . The system of  claim 71 , wherein said matrix comprises a silica matrix.  
     
     
         73 . The system of  claim 72 , wherein said silica matrix comprises glass wool.  
     
     
         74 . The system of  claim 71 , wherein said matrix comprises a solid support having poly-T oligonucleotides coupled to said solid support.  
     
     
         75 . A miniature fluidic system, comprising: 
 a body having at least a first chamber of fluidly connected to a second chamber by a fluid passage;    a sample inlet, fluidly connected to said first chamber, for introducing a fluid sample into said system;    a differential pressure delivery system for maintaining said first chamber at a first pressure and said second chamber at a second pressure, said first pressure being greater than ambient pressure and said second pressure being greater than said first pressure, whereby when said second chamber is brought to ambient pressure, said first pressure forces a liquid sample in said first chamber into said second chamber.    
     
     
         76 . The system of  claim 75 , wherein said differential pressure delivery system comprises: 
 a pressure source;    at least first and second passages fluidly connecting said pressure source to said at least first and second chambers, respectively;    a first fluidic resistance disposed in said first passage between said pressure source and said first chamber, said first fluidic resistance transforming a pressure from said pressure source to said first pressure;    a second fluidic resistance disposed in said second passage between said pressure source and said second chamber, said second fluidic resistance transforming said pressure from said pressure source to said second pressure; and    first and second openable closures in said first and second chambers, respectively, whereby opening of said first or second closures allows said first or second chambers to achieve ambient pressure.    
     
     
         77 . The system of  claim 76 , wherein said first and second fluidic resistances independently comprise one or more fluid passages connecting said first and second passages to said first and second chambers, said first fluidic resistance having a smaller cross-sectional area than said second fluidic resistance.  
     
     
         78 . The system of  claim 76 , wherein said first and second fluidic resistances independently comprise one or more fluid passages connecting said first and second passages to said first and second chambers, said fluid passages of said first fluidic resistance having a greater length than said fluid passages of said second fluidic resistance.  
     
     
         79 . A miniature fluidic system, comprising: 
 a body having at least a first chamber fluidly connected to a second chamber;    a sample inlet, fluidly connected to said first chamber, for introducing a fluid sample into said at first chamber;    a differential pressure delivery source for maintaining said first chamber at a first pressure and said second chamber at a second pressure, said second pressure being less than ambient pressure and said first pressure being less than said second pressure, whereby when said first chamber is brought to ambient pressure, said second pressure draws a liquid sample in said first chamber into said second chamber.    
     
     
         80 . The system of  claim 79 , wherein said at least a first chamber is fluidly connected to said second chamber by a fluid passage.  
     
     
         81 . The system of  claim 80 , wherein said differential pressure delivery system comprises: 
 a pressure source;    at least first and second passages fluidly connecting said pressure source to said at least first and second chambers, respectively;    a first fluidic resistance disposed in said first passage between said pressure source and said first chamber, said first fluidic resistance transforming a pressure from said pressure source to said first pressure;    a second fluidic resistance disposed in said second passage between said pressure source and said second chamber, said second fluidic resistance transforming said pressure from said pressure source to said second pressure; and    first and second openable closures in said first and second chambers, respectively, whereby opening of said first or second closures allows said first or second chambers to achieve ambient pressure.    
     
     
         82 . The system of  claim 81 , wherein said first and second fluidic resistances independently comprise one or more fluid passages connecting said first and second passages to said first and second chambers, said first fluidic resistance having a larger cross-sectional area than said second fluidic resistance.  
     
     
         83 . The system of  claim 81 , wherein said first and second fluidic resistances independently comprise one or more fluid passages connecting said first and second passages to said first and second chambers, said first fluidic resistance comprising passages having a shorter length than said channels of said second fluidic resistance.  
     
     
         84 - 91 . (canceled)