DNA analyzer

Abstract

Aspects of the disclosure provide a microfluidic chip to facilitate DNA analysis. The microfluidic chip includes a first domain configured for polymerase chain reaction (PCR) amplification of DNA fragments, a dilution domain coupled to the first domain to dilute a PCR mixture received from the first domain, and a second domain that is coupled to the dilution domain so as to receive the amplified DNA fragments. The second domain includes a separation channel that is configured to perform electrophoretic separation of the amplified DNA fragments. In addition, the disclosure provides a DNA analyzer to act on the microfluidic chip to perform an integrated single chip DNA analysis.

1 . A microfluidic chip, comprising:
 a first domain configured for polymerase chain reaction (PCR) amplification of DNA fragments;   a dilution domain that is fluidically coupled to the first domain and is configured to dilute a PCR mixture received from the first domain with a dilutant; and   a second domain that is fluidically coupled to the dilution domain so as to receive the amplified DNA fragments, the second domain including a separation channel that is configured to perform electrophoretic separation of the amplified DNA fragments.   
     
     
         2 . The microfluidic chip of  claim 1 , wherein the first domain comprises:
 a reservoir configured to receive a template DNA and reagents, and amplify the DNA fragments based on the template DNA and the reagents.   
     
     
         3 . The microfluidic chip of  claim 2 , further comprising:
 a plurality of inlets configured to input the template DNA and the reagents into the microfluidic chip.   
     
     
         4 . The microfluidic chip of  claim 1 , wherein the second domain comprises:
 an injection channel configured to inject the amplified DNA fragments into the separation channel by electro-kinetic injection.   
     
     
         5 . The microfluidic chip of  claim 1 , further comprising:
 a plurality of electrode reservoirs for applying an electric field over the separation channel.   
     
     
         6 . The microfluidic chip of  claim 1 , wherein in the dilution domain, the PCR mixture and the dilutant are mixed according to a ratio from 1:5 to 1:20. 
     
     
         7 . A DNA analyzer that is configured to receive and act on the microfluidic chip of  claim 1  to perform DNA analysis. 
     
     
         8 . A cartridge, comprising:
 a sample acceptor configured to extract a template DNA;   a microfluidic chip having a first domain and a second domain coupled to the first domain, wherein the first domain is configured to perform polymerase chain reaction (PCR) amplification of DNA fragments based on the template DNA, and the second domain has a separation channel that is configured to perform electrophoretic separation of the amplified DNA fragments.   
     
     
         9 . The cartridge of  claim 8 , further comprising:
 a reagent carrier configured to carry reagents for the PCR amplification, and solutions for the electrophoretic separation.   
     
     
         10 . The cartridge of  claim 8 , wherein the sample acceptor is configured to extract the template DNA by at least one of a silica solid phase extraction, and a liquid phase enzymatic DNA isolation. 
     
     
         11 . The cartridge of  claim 8 , wherein the sample acceptor comprises:
 a well having a liquid phase mixture to extract the template DNA.   
     
     
         12 . The cartridge of  claim 11 , wherein the liquid phase mixture is sealed in the well before the extraction. 
     
     
         13 . The cartridge of  claim 9 , wherein the first domain of the microfluidic chip further comprises:
 a reservoir configured to receive the extracted template DNA and the reagents, and amplify the DNA fragments based on the template DNA and the reagents.   
     
     
         14 . The cartridge of  claim 9 , wherein the microfluidic chip further comprises:
 a plurality of inlets configured to input the template DNA and the reagents kits into the microfluidic chip.   
     
     
         15 . The cartridge of  claim 8 , wherein the second domain of the microfluidic chip comprises:
 an injection channel configured to inject the amplified DNA fragments into the separation channel by electro-kinetic injection.   
     
     
         16 . The cartridge of  claim 8 , wherein the microfluidic chip further comprises:
 a plurality of electrode reservoirs for applying an electric field over the separation channel.   
     
     
         17 . The cartridge of  claim 8 , wherein the microfluidic chip further comprises:
 a waste outlet to drain liquid out of the microfluidic chip.   
     
     
         18 . The cartridge of  claim 8 , wherein the microfluidic chip further comprises:
 a dilution domain coupled to the first domain and the second domain, the dilution domain diluting a PCR mixture received from the first domain with a dilutant, and providing the diluted PCR mixture to the second domain.   
     
     
         19 . The cartridge of  claim 18 , wherein in the dilution domain, the PCR mixture and the dilutant are mixed according to a ratio from 1:5 to 1:20. 
     
     
         20 . A DNA analyzer that is configured to receive the cartridge of  claim 8 , and act on the microfluidic chip to perform DNA analysis. 
     
     
         21 . A DNA analyzer, comprising:
 an interface for coupling a microfluidic chip to the DNA analyzer, wherein the microfluidic chip includes:
 a first domain configured for polymerase chain reaction (PCR) amplification of DNA fragments, the DNA fragments being labeled with fluorescent labels; and 
 a second domain that is coupled to the first domain so as to receive the amplified DNA fragments, the second domain including a separation channel that is configured to perform electrophoretic separation of the amplified DNA fragments; 
   a pressure module configured to flow liquid in the microfluidic chip;   a thermal module configured to induce thermal cycles at the first domain of the microfluidic chip for the PCR amplification;   a power module configured to generate voltages to be applied to the second domain of the microfluidic chip for the electrophoretic separation;   a detection module configured to excite the fluorescent labels to emit fluorescence, and detect the emitted fluorescence; and   a controller module configured to control the pressure module, the thermal module, the power module, and the detection module according to a control procedure to act on the microfluidic chip for a single-chip DNA analysis.   
     
     
         22 . The DNA analyzer of  claim 21 , wherein the pressure module further comprises:
 a plurality of pumps configured to inject a template DNA and reagents in the microfluidic chip.   
     
     
         23 . The DNA analyzer of  claim 22 , wherein the controller module is configured to respectively control the plurality of pumps. 
     
     
         24 . The DNA analyzer of  claim 21 , wherein the pressure module further comprises:
 a vacuum pump configured to control a membrane valve on the microfluidic chip.   
     
     
         25 . The DNA analyzer of  claim 21 , wherein the thermal module further comprises:
 a heating unit configured to direct heat to the first domain;   a cooling unit configured to disperse heat from the first domain; and   a sensing unit configured to measure a temperature at the first domain.   
     
     
         26 . The DNA analyzer of  claim 25 , wherein the heating unit includes an infrared light source to heat the first domain. 
     
     
         27 . The DNA analyzer of  claim 25 , wherein the sensing unit includes an infrared pyrometer to measure the temperature. 
     
     
         28 . The DNA analyzer of  claim 25 , wherein the sensing unit measures a temperature within a thermal coupler reservoir in the first domain, the thermal coupler reservoir being thermally coupled with a reaction reservoir in the first domain configured for the PCR amplification. 
     
     
         29 . The DNA analyzer of  claim 21 , wherein the detection module further comprises:
 a laser module configured to emit a laser beam;   a detection module configured to detect fluorescence; and   a set of optics to direct the laser beam to the separation channel to excite the fluorescent labels to emit fluorescence, and direct the excited fluorescence to the detection module for detection.   
     
     
         30 . The DNA analyzer of  claim 21 , further comprising at least one of:
 a barcode reader configured to read a barcode to identify a DNA sample; and   a radio frequency identification (RFID) reader configured to read a RFID tag to identify a DNA sample.   
     
     
         31 . The DNA analyzer of  claim 21 , further comprising:
 a magnetic module configured to control magnetic beads used in a magnetic solid phase of a DNA analysis process.   
     
     
         32 . The DNA analyzer of  claim 21 , wherein the microfluidic chip further comprises:
 a dilution domain coupled to the first domain and the second domain, the dilution domain diluting a PCR mixture received from the first domain with a dilutant, and providing the diluted PCR mixture to the second domain.   
     
     
         33 . The DNA analyzer of  claim 32 , wherein in the dilution domain, the PCR mixture and the dilutant are mixed according to a ratio from 1:5 to 1:20. 
     
     
         34 . A method for DNA analysis, comprising:
 inducing thermal cycles in a first domain of a microfluidic chip for PCR amplification of DNA fragments;   inducing liquid flow to move the amplified DNA fragments from the first domain to a second domain of the microfluidic chip having a separation channel for electrophoretic separation;   inducing an electric field over the separation channel to separate the DNA fragments by sizes; and   detecting the separated DNA fragments.   
     
     
         35 . The method of  claim 34 , further comprising:
 maintaining a temperature for enzymatic DNA extraction to extract a template DNA.   
     
     
         36 . The method of  claim 35 , further comprising:
 injecting reagents into a reservoir in the first domain for the PCR amplification; and   injecting the template DNA into the reservoir for the PCR amplification.   
     
     
         37 . The method of  claim 34 , further comprising:
 maintaining a temperature in the separation channel.   
     
     
         38 . The method of  claim 34 , wherein inducing the liquid flow to move the amplified DNA fragments from the first domain to the second domain of the microfluidic chip having the separation channel for electrophoretic separation, further comprises:
 diluting the amplified DNA fragments with a dilution solution; and   electro-kinetic injecting the DNA fragments into the separation channel.   
     
     
         39 . The method of  claim 34 , wherein the amplified DNA fragments are tagged with fluorescent labels, and detecting the separated DNA fragments further comprises:
 emitting a laser beam;   directing the laser beam to the separation channel to excite the fluorescent labels to emit fluorescence;   collecting the emitted fluorescence; and   returning the collected fluorescence for detection.   
     
     
         40 . The method of  claim 38 , further comprising:
 adding an internal lane standard (ILS) with the amplified DNA fragments to assist a size measurement.   
     
     
         41 . The method of  claim 38 , wherein diluting the amplified DNA fragments with the dilution solution further comprises:
 diluting a PCR mixture received from the first domain with the dilution solution according to a ratio of 1:5 to 1:20 (one part of PCR mixture to 5-20 parts of dilution solution).