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 processing a plurality of nucleic acid-containing samples, the system comprising:
a first module configured to extract nucleic acids from the plurality of nucleic acid-containing samples,
a second module configured to amplify the nucleic acid extracted from the plurality of nucleic acid-containing samples, the first and second modules comprising:
a bay configured to removably receive a housing comprising a plurality of process chambers that are maintained at a same height relative to one another when the housing is received in the bay, the plurality of process chambers aligned along a first axis when the housing is received in the bay, the bay comprising one or more complementary registration members configured to receive the housing in a single orientation when the housing is received in the bay,
the first module further comprising a magnetic separator positioned to apply a magnetic force to a first side of the plurality of process chambers when the housing is received in the bay, the magnetic separator comprising one or more magnets aligned along a second axis parallel to the first axis when the housing is received in the bay, the one or more complementary registration members further configured to align the plurality of process chambers with the magnetic separator when the housing is received in the bay, and
the first module further comprising a heating assembly positioned adjacent to a second side of the plurality of process chambers opposite the first side when the housing is received in the bay, the heater assembly comprising one or more heaters aligned along a third axis parallel to the first axis when the housing is received in the bay, the heating assembly configured to heat a solution in the plurality of process chambers to between 50° C. and 85° C., the one or more complementary registration members configured to align the plurality of process chambers with the heater assembly when the housing is received in the bay; and
a liquid dispenser configured to move between a first location and a second location when the housing is received in the bay, the liquid dispenser configured to dispense at least a portion of the plurality of nucleic acid-containing samples and a plurality of magnetic binding particles when the housing is received in the bay and the liquid dispenser is in the first location, the liquid dispenser further configured to dispense the nucleic acid extracted from the plurality of nucleic-acid containing samples when the liquid dispenser is in the second location.
2. The system of claim 1 , wherein a sample of the plurality of nucleic acid-containing samples corresponds with a process chamber of the plurality of process chambers when the housing is received in the bay.
3. The system of claim 1 , wherein the liquid dispenser comprises one or more dispense heads configured to accept a pipette tip.
4. The system of claim 3 , wherein the liquid dispenser comprises four dispense heads and the housing comprises twelve process chambers, each dispense head configured to dispense a plurality of magnetic binding particles and at least a portion of one sample of the plurality of nucleic acid-containing samples into one of the twelve process chambers when the housing is received in the bay.
5. The system of claim 1 , further comprising a sample identification verifier configured to check an identity of each sample of the plurality of nucleic acid-containing samples, wherein the sample identification verifier is selected from the group consisting of an optical character reader, a bar code reader, and a radio frequency tag reader.
6. The system of claim 1 , further comprising electronic circuitry configured to control operation of the magnetic separator, the heater assembly, and the liquid dispenser.
7. The system of claim 6 , wherein the electronic circuitry is configured to cause the magnetic separator to apply a magnetic force to the plurality of process chambers when the housing is received in the bay.
8. The system of claim 6 , wherein the electronic circuitry is configured to cause the heater assembly to apply heat to the plurality of process chambers when the housing is received in the bay.
9. The system of claim 6 , wherein the electronic circuitry is configured to control motion of the liquid dispenser when the housing is received in the bay.
10. The system of claim 1 , further comprising one or more processors and at least one input device coupled to the one or more processors, the at least one input device selected from the group consisting of: a keyboard, a touch-sensitive surface configured to accept input from a stylus or a user's finger, a microphone, a track-pad, a retinal scanner, a fingerprint reader, a holographically projected interface, and a mouse.
11. The system of claim 10 , further comprising a communication interface coupled to the one or more processors, the communication interface being selected from the group consisting of: a serial connection, a parallel connection, a wireless network connection, a wired network connection, and one or more USB ports.
12. The system of claim 11 , further comprising a data storage medium configured to receive data from the one or more processors, the at least one input device, and the communication interface, the storage medium being selected from the group consisting of: a hard disk drive, an optical disk drive, a flash-card, a USB-drive, and a CD-Rom.
13. The system of claim 12 , further comprising at least one output device coupled to the one or more processors, the at least one output device being selected from a visual display, a printer, a holographic projection, and a speaker.
14. The system of claim 1 , further comprising more than one bay, each bay configured to removably receive a housing comprising a plurality of process chambers.
15. The system of claim 1 , wherein the number of nucleic acid-containing samples is twelve.
16. The system of claim 1 , further comprising an optical detection system configured to independently detect a plurality of fluorescent dyes at a plurality of different locations, wherein each fluorescent dye binds to a fluorescent polynucleotide probe or a fragment thereof.
17. The system of claim 16 , wherein the optical detection system selectively emits light in an absorption band of the plurality of fluorescent dyes and selectively detects light in an emission band of the plurality of fluorescent dyes.
18. The system of claim 16 , configured to carry out extraction, amplification, and detection of the plurality of nucleic acid-containing samples in less than an hour.
19. The system of claim 1 , further comprising a heater substrate comprising at least one heat source configured to apply heat at one or more selected times in order to apply thermocycling operations sufficient to amplify the nucleic acid extracted from the plurality of nucleic acid-containing samples.
20. The system of claim 19 , wherein the at least one heat source is configured to maintain a negligible temperature gradient across a reaction zone during the thermocycling operations, the reaction zone configured to receive the nucleic acid extracted from one of the plurality of nucleic acid-containing samples.
21. The system of claim 20 , wherein the at least one heat source is configured to maintain a negligible temperature gradient across each of a plurality of reaction zones during the thermocycling operations, each reaction zone configured to receive the nucleic acid extracted from one of the plurality of nucleic acid-containing samples.
22. A system for processing a plurality of nucleic acid-containing samples, the system comprising:
a first module configured to extract nucleic acids from the plurality of nucleic acid-containing samples, the first module comprising:
a bay configured to removably receive a housing comprising a plurality of process chambers that are maintained at a same height relative to one another when the housing is received in the bay, the plurality of process chambers aligned along a first axis when the housing is received in the bay, the bay comprising one or more complementary registration members configured to receive the housing in a single orientation when the housing is received in the bay,
a magnetic separator positioned to apply a magnetic force to a first side of the plurality of process chambers when the housing is received in the bay, the magnetic separator comprising one or more magnets aligned along a second axis parallel to the first axis when the housing is received in the bay, the one or more complementary registration members further configured to align the plurality of process chambers with the magnetic separator when the housing is received in the bay, and
a heating assembly positioned adjacent to a second side of the plurality of process chambers opposite the first side when the housing is received in the bay, the heater assembly comprising one or more heaters aligned along a third axis parallel to the first axis when the housing is received in the bay, the heating assembly configured to heat a solution in the plurality of process chambers to between 50° C. and 85° C., the one or more complementary registration members configured to align the plurality of process chambers with the heater assembly when the housing is received in the bay;
a second module configured to amplify the nucleic acid extracted from the plurality of nucleic acid-containing samples; and
a liquid dispenser configured to move between a first location and a second location when the housing is received in the bay, the liquid dispenser configured to dispense at least a portion of the plurality of nucleic acid-containing samples and a plurality of magnetic binding particles when the housing is received in the bay and the liquid dispenser is in the first location, the liquid dispenser further configured to dispense the nucleic acid extracted from the plurality of nucleic-acid containing samples into the second module when the liquid dispenser is in the second location.
23. The system of claim 22 , wherein the liquid dispenser comprises one or more dispense heads configured to accept a pipette tip.
24. The system of claim 23 , wherein the liquid dispenser comprises four dispense heads and the housing comprises twelve process chambers, each dispense head configured to dispense a plurality of magnetic binding particles and at least a portion of one sample of the plurality of nucleic acid-containing samples into one of the twelve process chambers when the housing is received in the bay.
25. The system of claim 22 , further comprising electronic circuitry configured to control operation of the magnetic separator, the heater assembly, and the liquid dispenser.
26. The system of claim 22 , further comprising one or more processors and at least one input device coupled to the one or more processors, the at least one input device selected from the group consisting of: a keyboard, a touch-sensitive surface configured to accept input from a stylus or a user's finger, a microphone, a track-pad, a retinal scanner, a fingerprint reader, a holographically projected interface, and a mouse.
27. The system of claim 22 , wherein the first module comprises more than one bay, each bay configured to removably receive a housing comprising a plurality of process chambers.
28. The system of claim 22 , wherein the number of nucleic acid-containing samples is twelve.
29. The system of claim 22 , further comprising an optical detection system configured to independently detect a plurality of fluorescent dyes at a plurality of different locations, wherein each fluorescent dye binds to a fluorescent polynucleotide probe or a fragment thereof.
30. The system of claim 22 , further comprising a heater substrate comprising at least one heat source configured to apply heat at one or more selected times in order to apply thermocycling operations sufficient to amplify the nucleic acid extracted from the plurality of nucleic acid-containing samples.