Integrated apparatus for performing nucleic acid extraction and diagnostic testing on multiple biological samples
The technology described herein generally relates to systems for extracting polynucleotides from multiple samples, particularly from biological samples, and additionally to systems that subsequently amplify and detect the extracted polynucleotides. The technology more particularly relates to microfluidic systems that carry out PCR on multiple samples of nucleotides of interest within microfluidic channels, and detect those nucleotides.
1. A system for analyzing a plurality of samples comprising nucleic acids, the system configured to receive a plurality of process chambers and a plurality of amplification chambers, the plurality of process chambers configured to receive the plurality of samples, the plurality of amplification chambers configured to receive nucleic acids from the plurality of samples, the system comprising:
one or more complementary registration members that receive the plurality of process chambers and the plurality of amplification chambers in a single orientation when the plurality of process chambers and the plurality of amplification chambers are received in the system;
a magnetic separator positioned to apply a magnetic force to at least one process chamber of the plurality of process chambers when the plurality of process chambers is received in the system;
a first set of one or more heaters in thermal communication with the plurality of process chambers when the plurality of process chambers is received in the system, the first set of one or more heaters configured to independently heat solutions in the plurality of process chambers to a temperature between 50° C. and 85° C. to release nucleic acids from the plurality of samples;
an optical detection system;
a second set of heaters configured to cycle between at least two temperatures; and
an automated mechanism configured to, under software control, position the plurality of amplification chambers in thermal communication with the second set of heaters, wherein the second set of heaters is configured to maintain a substantially uniform temperature at the at least two temperatures in at least one amplification chamber of the plurality of amplification chambers, and wherein the second set of heaters is configured to perform independent amplification reactions in the plurality of amplification chambers when the plurality of amplification chambers is received in the system.
2. The system of claim 1 , wherein the automated mechanism is further configured to position the plurality of amplification chambers in optical communication with the optical detection system.
3. The system of claim 1 , wherein the one or more complementary registration members are configured to align the plurality of process chambers with the magnetic separator and the first set of one or more heaters when the plurality of process chambers is received in the system.
4. The system of claim 1 , wherein the system is configured to dispense a wash buffer into the at least one process chamber while the magnetic separator applies a magnetic force to the at least one process chamber.
5. The system of claim 1 , wherein the system is configured to dispense a release buffer into the at least one process chamber before the first set of one or more heaters applies heat to a solution in the at least one process chamber.
6. The system of claim 1 , further comprising a liquid dispenser configured to withdraw the nucleic acids from the plurality of process chambers.
7. The system of claim 6 , wherein the liquid dispenser is further configured to dispense the nucleic acids into a plurality of openings, each opening of the plurality of openings in communication with an amplification chamber of the plurality of amplification chambers.
8. The system of claim 1 , further comprising a liquid dispenser configured to dispense a plurality of magnetic binding particles into the plurality of process chambers.
9. The system of claim 8 , wherein the magnetic separator is configured to hold the plurality of magnetic binding particles against surfaces of the plurality of process chambers.
10. The system of claim 8 , wherein the plurality of magnetic binding particles are in suspension in solutions in the plurality of process chambers before the magnetic separator applies the magnetic force to the at least one process chamber.
11. The system of claim 10 , wherein the magnetic separator is configured to collect the suspended plurality of magnetic binding particles in a location inside the at least one process chamber.
12. The system of claim 8 , wherein the magnetic separator is configured to concentrate the plurality of magnetic binding particles in a location inside each of the plurality of process chambers.
13. The system of claim 1 , wherein the magnetic separator is configured to maintain one or more magnets between about 1 mm and about 2 mm away from the plurality of process chambers.
14. The system of claim 1 , wherein the magnetic separator comprises a plurality of discrete magnets configured to apply a magnetic force to the plurality of process chambers.
15. The system of claim 14 , wherein the magnetic separator comprises one or more magnets, and wherein one pole of the one or more magnets faces toward the first set of one or more heaters and the other pole of the one or more magnets faces away from the first set of one or more heaters.
16. The system of claim 1 , wherein the first set of one or more heaters comprises a heat block formed from a single piece of metal.
17. The system of claim 16 , wherein the heat block is shaped to conform to the shape of the plurality of process chambers to increase a surface area of the heat block that is in contact with the plurality of process chambers during heating of the plurality of process chambers.
18. The system of claim 1 , wherein thermal energy and magnetic energy are provided to the plurality of process chambers without moving the plurality of process chambers to a different location to perform heating or magnetic separation.
19. The system of claim 1 , wherein the plurality of process chambers comprises twelve process chambers.
20. The system of claim 1 , wherein each of the plurality of amplification chambers is in communication with an opening of a plurality of openings, the plurality of openings configured to receive the nucleic acid from the plurality of samples.
21. The system of claim 1 , wherein the optical detection system is configured to independently detect a plurality of fluorescent dyes in the plurality of amplification chambers.
22. The system of claim 21 , wherein the optical detection system is configured to selectively emit light in an absorption band of the plurality of fluorescent dyes and selectively detect light in an emission band of the plurality of fluorescent dyes.
23. The system of claim 21 , wherein the system is configured to extract, amplify, and detect nucleic acids in the plurality of samples in less than an hour.
24. The system of claim 1 , wherein the second set of heaters is configured to maintain a negligible temperature gradient across each of the plurality of amplification chambers during thermocycling operations.
25. The system of claim 1 , wherein the system is configured to move the plurality of amplification chambers toward the second set of heaters.
26. The system of claim 25 , wherein movement of the plurality of amplification chambers toward the second set of heaters is a spring-loaded downward movement.
27. The system of claim 1 , wherein the system is configured to apply a downward pressure that moves the plurality of amplification chambers toward the second set of heaters.