Sample preparation, processing and analysis systems
This disclosure provides an integrated and automated sample-to-answer system that, starting from a sample comprising biological material, generates a genetic profile in less than two hours. In certain embodiments, the biological material is DNA and the genetic profile involves determining alleles at one or a plurality of loci (e.g., genetic loci) of a subject, for example, an STR (short tandem repeat) profile, for example as used in the CODIS system. The system can perform several operations, including (a) extraction and isolation of nucleic acid; (b) amplification of nucleotide sequences at selected loci (e.g., genetic loci); and (c) detection and analysis of amplification product. These operations can be carried out in a system that comprises several integrated modules, including an analyte preparation module; a detection and analysis module and a control module.
1. A system comprising:
a cartridge comprising:
one or more chambers wherein each of the one or more chambers is closed and fluidically isolated with a friable seal;
valves configured to selectively open to permit fluid flow to the one or more chambers; and
one or more puncturing elements configured to respectively puncture the friable seal of each of the one or more chambers; and
a cartridge module comprising:
a cartridge receptacle configured to removable receive the cartridge;
a first assembly positioned on a first side of the cartridge receptacle and comprising a first pressure manifold comprising a first plurality of tubes in fluid communication with a pressure source, wherein the first pressure manifold is engageable with the first side of the cartridge in a state of the cartridge received by the cartridge receptacle, such that the one or more chambers are in fluid communication with the pressure source; and
a second assembly positioned on a second side of the cartridge receptacle opposite the first side of the cartridge receptacle, the second assembly comprising a second pressure manifold comprising a second plurality of tubes, each of the second plurality of tubes being, independently, in fluid communication with the pressure source or with a second pressure source, wherein the second pressure manifold is engageable with the second side of the cartridge in a state of the cartridge received by the cartridge receptacle, such that the valves are, independently, placed in fluid communication with the pressure source or with the second pressure source for independent pneumatic actuation of the valves, and
wherein, in a state of the cartridge engaged with the first assembly and the second assembly, the one or more puncturing elements puncture the friable seal of each of one or more chambers;
wherein each of the one or more chambers is in fluid communication with respective first chamber ports and second chamber ports; and
wherein in a state of the friable seal punctured by the one or more puncturing elements, a fluid flow path through each of the one or more chambers and in fluid communication with the respective first chamber ports and second chamber ports of each of the one or more chambers is created.
2. The system of claim 1 , wherein the cartridge is configured to be removably received by the cartridge receptacle with a first side of the cartridge facing the first side of the cartridge receptacle and second side of the cartridge facing the second side of the cartridge receptacle opposite the first side of the cartridge receptacle.
3. The system of claim 2 further comprising an elongation or moving member coupled to one or both of the first assembly and the second assembly, the elongation or moving member comprising a piston, the movement of which moves one or both of the first pressure manifold and the second pressure manifold towards the cartridge receptacle.
4. The system of claim 3 , wherein movement of the piston moves one or both of the first pressure manifold and the second pressure manifold towards the cartridge in a state of the cartridge received by the cartridge receptacle, so as to engage one or both of the first pressure manifold and the second pressure manifold with the cartridge.
5. The system of claim 1 , wherein the cartridge further comprises:
fluidic channels, wherein the valves are disposed in the fluidic channels;
a first plurality of ports on the first side of the cartridge and in fluid communication with the fluidic channels, respectively, wherein the first plurality of tubes are aligned with respective ports of the first plurality of ports on the first side of the cartridge, in a state of the cartridge received in the cartridge receptacle, such that the one or more chambers are placed in fluid communication with the pressure source upon engaging the first plurality of tubes with the respective ports of the first plurality of ports on the first side of the cartridge; and
a second plurality of ports on the second side of the cartridge opposite the first side of the cartridge and in fluid communication with the valves, respectively, wherein the second plurality of tubes are aligned with respective ports of the second plurality of ports on the second side of the cartridge, in a state of the cartridge received in the cartridge receptacle, such that each of the valves are, independently, placed in fluid communication with the pressure source or the second pressure source upon engaging the second plurality of tubes with the respective ports of the second plurality of ports on the second side of the cartridge, such that each of the valves is selectively actuatable, independent of other valves, sa as to selectively open to permit fluid flow to the one or more chambers through the fluidic channels.
6. The system of claim 5 , wherein the cartridge further comprises:
a sample receptacle having a sample disposed therein; and
one or more compartments having reagent disposed therein,
wherein the one or more chambers are in fluid communication with the sample receptacle and the one or more compartments, the fluidic channels connecting the sample receptacle and the one or more compartments to the one or more chambers.
7. A system comprising:
a cartridge comprising:
a sample receptacle having a sample disposed therein;
one or more compartments having reagent disposed therein;
one or more chambers are in fluid communication with the sample receptacle and the one or more compartments, wherein each of the one or more chambers is closed and fluidically isolated with a friable seal;
fluidic channels connecting the sample receptacle and the one or more compartments to the one or more chambers, the fluidic channels comprising valves configured to selectively open to permit fluid flow to the one or more chambers through the fluidic channels;
one or more puncturing elements configured to respectively puncture the friable seal of each of the one or more chambers;
a first plurality of ports on a first side of the cartridge and in fluid communication with the fluidic channels, respectively; and
a second plurality of ports on a second side of the cartridge opposite the first side of the cartridge, each of the second plurality of ports in fluid communication with a respective one of the valves; and
a cartridge module comprising:
a cartridge receptacle configured to removably receive the cartridge in a position with the first side of the cartridge disposed on a first side of the cartridge receptacle and the second side of the cartridge disposed on a second side of the cartridge receptacle opposite the first side of the cartridge receptacle;
a first assembly positioned on the first side of the cartridge receptacle adjacent to the first side of the cartridge in a state of the cartridge received by the cartridge receptacle, the first assembly comprising a first pressure manifold comprising a first plurality of tubes configured to be aligned with respective ports on the first side of the cartridge such that the one or more chambers are placed in fluid communication with a pressure source upon engaging the first plurality of tubes with the respective ports on the first side of the cartridge;
a second assembly positioned on a second side of the cartridge receptacle adjacent to the second side of the cartridge in a state of the cartridge received by the cartridge receptacle, the second assembly comprising a second pressure manifold comprising a second plurality of tubes configured to be aligned with respective ports on the second side of the cartridge, each of the second plurality of tubes being configured to be placed, independently, in fluid communication with the pressure source or a second pressure source, such that each of the valves are, independently, placed in fluid communication with the pressure source ore the second pressure source upon engaging the second plurality of tubes with the respective ports on the second side of the cartridge, such that each of the valves is selectively actuatable, independent of other valves, so as to selectively open and permit fluid flow to the one or more chambers through the fluidic channels; and
an elongation or moving member coupled to one or both of the first assembly and the second assembly, the elongation or moving member comprising a piston, the movement of which moves on or both of the first pressure manifold and the second pressure manifold towards the cartridge, in a state of the cartridge received by the cartridge receptacle, sa as to engage the first plurality of tubes with the respective ports on the first side of the cartridge and/or to engage the second plurality of tubes with the respective ports on the second side of the cartridge,
wherein, in a state of the cartridge received by the cartridge receptacle, movement of one or both of the first assembly and the second assembly towards the cartridge, causes the one of more puncturing elements to puncture the friable seal of each of one or more chambers;
wherein in each of the one or more chambers in in fluid communication with respective first chamber ports and second chamber ports; and
wherein in a state of the friable seal punctured by the one or more puncturing elements, a fluid flow path through each of the one or more chambers and in fluid communication with the respective first chamber ports and second chamber ports of each of the one or more chambers is created.