Multi-layer microfluidic devices
DCFirst Claim
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1. A microfluidic system comprising:
- a body structure having at least first, second and third substrate layers, the second substrate layer disposed on top of the first substrate layer and the third substrate layer disposed on top cf the second substrate layer;
at least first, second and third ports disposed in the body structure;
at least first, and second microscale channel networks, the first channel network disposed between the first and second substrate layers, and being in fluid communication with the first and second ports, but not the third port, and the second channel network disposed between the second and third layers, and being in fluid communication with the first and third ports, but not the second port; and
a material transport system operably linked to each of the first, second and third ports, for selectively controlling movement of material in the first and second channel networks, the material transport system comprises first, second and third electrodes in separate electrical contact with each of the first, second and third ports, respectively, and an electrical controller for concomitantly delivering a separate voltage to each of the first, second and third electrodes.
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Abstract
The present invention provides multi-layer microfluidic systems, by providing additional substrate layers, e.g., third, fourth, fifth and more substrate layers, mated with the typically described first and second layers. Microfabricated elements, e.g., grooves, wells and the like, are manufactured into the surfaces between the various substrate layers. These microfabricated elements define the various microfluidic aspects or structures of the overall device, e.g., channels, chambers and the like. In preferred aspects, a separate microscale channel network is provided between each of the substrate layers.
592 Citations
39 Claims
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1. A microfluidic system comprising:
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a body structure having at least first, second and third substrate layers, the second substrate layer disposed on top of the first substrate layer and the third substrate layer disposed on top cf the second substrate layer;
at least first, second and third ports disposed in the body structure;
at least first, and second microscale channel networks, the first channel network disposed between the first and second substrate layers, and being in fluid communication with the first and second ports, but not the third port, and the second channel network disposed between the second and third layers, and being in fluid communication with the first and third ports, but not the second port; and
a material transport system operably linked to each of the first, second and third ports, for selectively controlling movement of material in the first and second channel networks, the material transport system comprises first, second and third electrodes in separate electrical contact with each of the first, second and third ports, respectively, and an electrical controller for concomitantly delivering a separate voltage to each of the first, second and third electrodes. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15)
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16. A microfluidic device comprising:
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a body structure comprising at least first, second and third substrate layers wherein the second substrate layer comprises an upper planar surface and a lower planar surface, the second substrate layer disposed on top of the first substrate layer and the third substrate layer disposed on top of the second substrate layer;
at least first and second microscale channel networks, the first channel network disposed between the first and second substrate layers, and the second channel network disposed between the second and third layers, wherein the first channel network is microfabricated in the bottom surface of the second substrate layer, and the second channel network is fabricated in the top surface of the second substrate layer; and
at least one fluid passage disposed through the second substrate layer providing fluid communication between the first channel network and the second channel network. - View Dependent Claims (22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39)
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17. A microfluidic device, comprising:
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a body structure comprising first, second and third planar substrates, each of the substrates having upper and lower planar surfaces, wherein the upper surface of the first substrate is mated with the lower surface of the second substrate and the upper surface of the second substrate is mated with the lower surface of the third substrate, and a first and second ports disposed through the second and third substrates, and a third port disposed through the third substrate;
a first channel network having at least first and second termini, the first channel network defined between the upper surface of the first substrate and the lower surface of the second substrate, the first channel network being in fluid communication with the first port at a first terminus of the first channel network and in fluid communication with the second port at a second terminus of the first channel network; and
a second channel network having at least first and second termini, the second channel network defined between the upper surface of the second substrate and the lower surface of the third substrate, the second channel network in fluid communication with the first port at the first terminus of the second channel network and in fluid communication with the third port at the second terminus of the second channel network.
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18. A method of performing a plurality of different analyses on a single fluid sample, the method comprising:
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providing a microfluidic device having a body structure comprising at least first, second and third substrate layers, the second substrate layer disposed on top of the first substrate layer and the third substrate layer disposed on top of the second substrate layer, and at least first and second microscale channel networks, the first channel network disposed between the first and second substrate layers, and being in fluid communication with first and second ports disposed in the body structure, and the second channel network disposed between the second and third layers, and being in fluid communication with the first port and a third port disposed in the body structure;
placing the fluid sample into the first port;
transporting the fluid sample through each of the first and second channel networks, each of the channel networks performing a different reaction on the fluid sample;
detecting a result of the reaction performed in each of the two channel networks.
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19. A microfluidic device for sequencing a target nucleic acid, comprising:
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a body structure comprising at least five substrate layers, four separation channels, each of the separation channels disposed between two different substrate layers;
a common sample reservoir connected to each of the four separation channels via four separate sample introduction channels;
four reagent channels, each reagent channel independently connecting each of the four sample introduction channels with a separate one of four separate reagent reservoirs disposed in the body structure, each of the four separate reagent reservoirs comprising a separate dideoxynucleotide disposed therein.
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20. A microfluidic device for sequencing a target nucleic acid, comprising:
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a body structure having at least first, second, third, fourth and fifth substrate layers, the second substrate layer disposed on top of the first substrate layer, the third substrate layer disposed on top of the second substrate layer, the fourth substrate layer disposed on top of the third substrate layer and the fifth substrate layer being disposed on top of the fourth substrate layer;
a first channel network disposed between the first substrate layer and the second substrate layer, the first channel network comprising a first channel connecting a first and a second reservoir disposed in the body structure, a first reagent channel connecting a third reservoir disposed in the body structure with the first channel between the first reservoir and the second reservoir, and a first separation channel connecting the first channel between the first reagent channel and the second reservoir;
a second channel network disposed between the second substrate layer and the third substrate layer, the second channel network comprising a second channel connecting the first and second reservoirs, a second reagent channel connecting a fourth reservoir disposed in the body structure with the second channel between the first and second reservoirs, and a second separation channel connecting a fifth reservoir with the second channel between the second reagent channel and the second reservoir;
a third channel network disposed between the third substrate layer and the fourth substrate layer, the third channel network comprising a third channel connecting the first and second reservoirs, a third reagent channel connecting a sixth reservoir with the third channel between the first and second reservoirs, and a third separation channel connecting a seventh reservoir with the third channel between the third reagent channel and the second reservoir;
a fourth channel network disposed between the fourth substrate layer and the fifth substrate layer, the fourth channel network comprising a fourth channel connecting the first and second reservoirs, a fourth reagent channel connecting an eighth reservoir disposed in the body structure with the fourth channel between the first and second reservoirs, and a fourth separation channel connecting a ninth reservoir disposed in the body structure, with the fourth channel between the fourth reagent channel and the second reservoir.
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21. A method of sequencing a target nucleic acid, comprising:
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providing microfluidic device having a body structure that comprises at least five substrate layers, at least four separation channels, each of the separation channels disposed between two different substrate layers, a common sample reservoir having a fluid sample containing the target nucleic acid disposed therein, the sample reservoir connected to each of the four separation channels via four separate sample introduction channels, and four reagent channels, each reagent channel independently connecting each of the four sample introduction channels with a separate one of four separate reagent reservoirs disposed in the body structure, each of the four separate reagent reservoirs containing a separate one of four reagent mixtures, each reagent mixture including four different nucleoside triphosphates, primer sequences complementary to the target nucleic acid sequence, and, a nucleic acid polymerase enzyme, and a separate dideoxynucleoside triphosphate;
separately combining the target nucleic acid with each of the four reagent mixtures in each of the four sample introduction channels;
sizing products of the combining step from each of the four sample introduction channels in each of the four separation channels, respectively; and
determining the sequence of the target nucleic acid from the size of the pro ducts as determined in the sizing step.
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Specification