# US 9,039,997 B2 · Microfluidic devices with removable cover and methods of fabrication and application > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,039,997 B2 - Document ID: US9039997B2 - Status: Granted - Kind: B2 - Application number: 13/499,879 - Filed: 2010-09-29 - Published: 2012-08-02 - Granted: 2015-05-26 - Earliest claimed: 2009-10-02 - Assignees: Fluidigm Corporation - Applicants: David Cohen; Andrew May; Martin Pieprzyk; Brian Fowler; Kim Huat Lee; Jun Yan; Ming Fang Zhou; Seng Beng Ng - Inventors: David Cohen; Andrew May; Martin Pieprzyk; Brian Fowler; Kim Huat Lee; Jun Yan; Ming Fang Zhou; Seng Beng Ng - Web page: https://patentgrep.com/patent/US9039997B2 ## CPC - B01L 3/5027: {by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip} - B01L 3/502738: {characterised by integrated valves (throttle valves in microfluidic sample containers B01L3/502746)} - B01L 9/527: {for microfluidic devices, e.g. used for lab-on-a-chip} - B01L 7/52: {with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples} - B01L 2200/12: Specific details about manufacturing devices - B01L 2300/045: whereby the whole cover is slidable - B01L 2300/0887: Laminated structure - B01L 2300/123: Flexible; Elastomeric - B01L 2400/0655: pinch valves - G01N 1/405: {by adsorption or absorption} - B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## Abstract The present invention includes microfluidic systems having a microfabricated cavity that may be covered with a removable cover, where the removable cover allows at least part of the opening of the microfabricated cavity to be exposed or directly accessed by an operator. The microfluidic systems comprise chambers, flow and control channels formed in elastomeric layers that may comprise PDMS. The removable cover comprises a thermoplastic base film bonded to an elastomer layer by an adhesive layer. When the removable cover is peeled off, the chamber is at least partially open to allow sample extraction from the chamber. The chamber may have macromolecular crystals formed inside or resulting contents from a PCR reaction. The invention also includes a method for making vias in elastomeric layers by using the removable cover. The invention further includes methods and devices for peeling the peelable cover or a removable component such as Integrated Heater Spreader. ## Claims ### Claim 1 A microfluidic system comprising: a base substrate; a sample holding layer formed on the base substrate, wherein the sample holding layer comprises a microfabricated cavity having an opening formed on a surface of the layer that faces opposite the substrate; a flow channel coupled to the cavity for delivering a reagent to the cavity; a control channel that intersects the flow channel and forms a deflectable membrane over at least a portion of the intersection, wherein actuation of the control channel causes deflection of the deflectable membrane to open or close the flow channel; and a removable cover having a cover layer with a first portion and a second portion, wherein the first portion and the second portion of the cover layer are coplanar when the cover layer is situated on the surface of the sample holding layer that faces opposite the substrate, and wherein the first portion of the cover layer is removable from the second portion of the cover layer to expose at least part of the opening in the microfabricated cavity while the second portion of the cover layer remains bonded to the sample holding layer. ### Claim 2 (depends on 1) The microfluidic system of claim 1, wherein the sample holding layer comprises an elastomeric material. ### Claim 3 (depends on 1) The microfluidic system of claim 1, wherein the sample holding layer comprises a non-elastomeric material. ### Claim 4 (depends on 3) The microfluidic system of claim 3, wherein the non-elastomeric material comprises glass. ### Claim 5 (depends on 1) The microfluidic system of claim 1, wherein at least part of the flow channel is formed in the sample holding layer. ### Claim 6 (depends on 1) The microfluidic system of claim 1, wherein the control channel is formed in the sample holding layer. ### Claim 7 (depends on 1) The microfluidic system of claim 1, wherein the microfabricated cavity is a reaction chamber. ### Claim 8 (depends on 1) The microfluidic system of claim 1, wherein the cover layer of the removable cover is a first elastomeric layer bonded to the sample holding layer, and the removable cover further comprises a second thermoplastic layer bonded to the first elastomeric layer by an adhesive layer. ### Claim 9 (depends on 8) The microfluidic system of claim 8, wherein the sample holding layer comprises the same material as the first elastomeric layer of the removable cover. ### Claim 10 (depends on 8) The microfluidic system of claim 8, wherein the second portion of the cover layer comprises a portion of the first elastomeric layer of the removable cover that does not overlap with the opening in the microfabricated cavity and that remains bonded to the sample holding layer after the first portion of the cover layer is removed from the second portion of the cover layer to expose at least part of the opening. ### Claim 11 (depends on 8) The microfluidic system of claim 8, wherein the first portion of the cover layer comprises a portion of the first elastomeric layer that overlaps with the opening in the microfabricated cavity and that remains bonded to the second thermoplastic layer when the cover is removed from the sample holding layer. ### Claim 12 (depends on 8) The microfluidic system of claim 8, wherein the first elastomeric layer comprises PDMS. ### Claim 13 (depends on 8) The microfluidic system of claim 8, wherein the second thermoplastic layer comprises PET. ### Claim 14 (depends on 8) The microfluidic system of claim 8, wherein the adhesive layer comprises an acrylic adhesive. ### Claim 15 (depends on 1) The microfluidic system of claim 1, wherein the base substrate comprises a rigid material. ### Claim 16 (depends on 15) The microfluidic system of claim 15, wherein the rigid material comprises glass. ### Claim 17 (depends on 1) The microfluidic system of claim 1, wherein the cavity has a volume ranging from 1 nL to 100 nL. ### Claim 18 (depends on 1) The microfluidic system of claim 1, wherein the sample holding layer comprises the same material as the cover layer of the removable cover. ### Claim 19 (depends on 1) The microfluidic system of claim 1, wherein the first portion of the cover layer overlaps with the opening in the microfabricated cavity and the second portion of the cover layer does not overlap with the opening in the microfabricated cavity. ### Claim 20 (depends on 1) The microfluidic system of claim 1, wherein the cover layer of the removable cover comprises PDMS. ### Claim 21 A method of microfabricating a microfluidic system with a removable cover, the method comprising: providing a base substrate; bonding a sample holding layer to the base substrate, wherein the sample holding layer comprises a microfabricated cavity or recess having an opening formed on a surface of the layer that faces opposite the substrate; microfabricating a flow channel coupled to the cavity for delivering a reagent to the cavity; microfabricating a control channel that intersects the flow channel and forms a deflectable membrane to open or close the flow channel, wherein actuation of the control channel causes deflection of the deflectable membrane to open or close the flow channel; and bonding a removable cover to the sample holding layer for sealing the cavity, the removable cover having a cover layer with a first portion and a second portion, wherein the first portion and the second portion of the cover layer are coplanar when the cover layer is situated on the surface of the sample holding layer that faces opposite the substrate, and wherein the first portion of the cover layer is removable from the second portion of the cover layer to expose at least part of the opening in the microfabricated cavity while the second portion of the cover layer remains bonded to the sample holding layer. ### Claim 22 (depends on 21) The method of claim 21, wherein the cover layer of the removable cover is a first elastomeric layer and the removable cover further comprises a second thermoplastic layer, the method further comprising: bonding the second portion of the cover layer to the sample holding layer; and bonding the second thermoplastic layer to the first elastomeric layer with an adhesive layer. ### Claim 23 (depends on 22) The method of claim 22, wherein the first portion of the cover layer comprises a portion of the first elastomeric layer that overlaps with the opening in the microfabricated cavity and that remains bonded to the second thermoplastic layer when the cover is removed from the sample holding layer. ### Claim 24 (depends on 22) The method of claim 22, wherein the second portion of the cover layer comprises a portion of the first elastomeric layer of the removable cover that does not overlap with the opening in the microfabricated cavity remains bonded to the sample holding layer after the first portion of the cover layer is removed from the second portion of the cover layer to expose at least part of the opening. ### Claim 25 (depends on 22) The method of claim 22, wherein the sample holding layer comprises the same elastomeric material as the first elastomeric layer of the removable cover. ### Claim 26 (depends on 25) The method of claim 25, wherein the first elastomeric layer comprises PDMS. ### Claim 27 (depends on 21) The method of claim 21, wherein the microfabricated cavity is a reaction chamber. ### Claim 28 (depends on 21) The method of claim 21, wherein the base substrate comprises a rigid material. ### Claim 29 (depends on 28) The method of claim 28, wherein the rigid material comprises glass. ### Claim 30 (depends on 21) The method of claim 21, wherein the sample holding layer comprises the same material as the cover layer of the removable cover. ### Claim 31 (depends on 21) The method of claim 21, wherein the cover layer of the removable cover comprises PDMS.