# US 9,752,978 B2 · Micromachined flow cell with freestanding fluidic tube > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,752,978 B2 - Document ID: US9752978B2 - Status: Granted - Kind: B2 - Application number: 14/376,430 - Filed: 2012-02-03 - Published: 2014-12-25 - Granted: 2017-09-05 - Earliest claimed: 2012-02-03 - Assignees: Agilent Technologies, Inc. - Applicants: Karsten Kraiczek; John Mannion; Kevin P. Killeen - Inventors: Karsten Kraiczek; John Mannion; Kevin P. Killeen - Web page: https://patentgrep.com/patent/US9752978B2 ## CPC - G01N 21/05: Flow-through cuvettes (G01N21/09 takes precedence; handling fluid samples G01N1/10) - B01L 3/502707: {characterised by the manufacture of the container or its components} - B01L 3/502715: {characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces} - B32B 37/18: involving the assembly of discrete sheets or panels only - B32B 38/10: Removing layers, or parts of layers, mechanically or chemically - G01N 30/74: Optical detectors {(measurement of intensity, velocity, spectral content, polarisation, or phase of infrared, visible or ultraviolet light G01J)} - G01N 33/54373: {involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings} - B01L 2300/0654: Lenses; Optical fibres - B01L 2300/0816: Cards, e.g. flat sample carriers usually with flow in two horizontal directions - B01L 2300/0838: Capillaries - B32B 2551/00: Optical elements - G01N 2021/0346: {Capillary cells; Microcells} - G01N 2021/052: {Tubular type; cavity type; multireflective} - G01N 2021/056: {Laminated construction} - G01N 2030/027: {Liquid chromatography} - G01N 2030/746: {detecting along the line of flow, e.g. axial} - G01N 2201/08: Optical fibres; light guides - Y10T 156/10: Methods of surface bonding and/or assembly therefor - 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) - B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE - B32B: LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM - Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION ## Abstract A micromachined flow cell includes a substrate and a freestanding tube, delimiting a fluidic conduit therein and being integrally formed from material of the substrate. ## Claims ### Claim 1 A flow cell, comprising: a substrate; and a freestanding tube delimiting a fluidic conduit therein and being integrally formed from material of the substrate, and surrounded by a gas atmosphere, wherein the freestanding tube comprises a section comprising a first end and a second end, and the section is configured for receiving electromagnetic radiation at the first end, and for emitting at the second end electromagnetic radiation having propagated through the fluidic conduit, and wherein the electromagnetic radiation coupled into the fluidic conduit undergoes total internal reflection at a boundary between an exterior surface of the freestanding tube and the surrounding gas atmosphere. ### Claim 2 (depends on 1) The flow cell according to claim 1, wherein the substrate and the freestanding tube are composed of the same material. ### Claim 3 (depends on 1) The flow cell according to claim 1, wherein the substrate comprises fused silica. ### Claim 4 (depends on 1) The flow cell according to claim 1, wherein the fluidic conduit has an internal volume in a range selected from the group consisting of: between 1 nl and 1000 nl, and between 10 nl and 100 nl. ### Claim 5 (depends on 1) The flow cell according to claim 1, wherein the substrate comprises a trench and two surface portions, and the freestanding tube extends along the trench and is connected to the two surface portions of the substrate delimiting the trench. ### Claim 6 (depends on 5) The flow cell according claim 5, wherein the freestanding tube between the two surface portions is U-shaped. ### Claim 7 (depends on 5) The flow cell according claim 5, wherein the substrate comprises two fluidic channels formed therein, and wherein each of the fluidic channels is directly fluidically coupled to a respective one of the two surface portions. ### Claim 8 (depends on 7) The flow cell according claim 7, wherein each of the two fluidic channels ends at a respective one of two fluidic interfaces of the substrate. ### Claim 9 (depends on 8) The flow cell according claim 8, wherein at least one of the two fluidic interfaces is spatially extended compared to the respective one of the two fluidic channels. ### Claim 10 (depends on 5) The flow cell according to claim 5, comprising a feature selected from the group consisting of: a cover sheet attached to a top surface of the substrate for capping the trench; a bottom sheet attached to a bottom surface of the substrate; and both of the foregoing. ### Claim 11 (depends on 1) The flow cell according to claim 1, further comprising a further substrate and a further freestanding tube delimiting a further fluidic conduit therein and being integrally formed from material of the further substrate, wherein the substrate and the further substrate are vertically stacked. ### Claim 12 (depends on 11) The flow cell according to claim 11, wherein the fluidic conduit is fluidically coupled to the further fluidic conduit. ### Claim 13 (depends on 11) The flow cell according to claim 11, wherein the substrate and the further substrate have the same external contour. ### Claim 14 (depends on 1) The flow cell according to claim 1, comprising at least one further freestanding tube delimiting at least one further fluidic conduit therein and being integrally formed from material of the same substrate as the freestanding tube. ### Claim 15 (depends on 14) The flow cell according to claim 14, wherein the at least one further fluidic conduit is fluidically connected in series with the fluidic conduit or is fluidically connected in parallel to the fluidic conduit. ### Claim 16 (depends on 14) The flow cell according to claim 14, wherein the at least one further fluidic conduit has another length than the fluidic conduit so that an effective interaction length (L1, L2) along which electromagnetic radiation propagating through the respective fluidic conduit interacts with a fluidic sample flowing through the respective fluidic conduit differs for the different fluidic conduits. ### Claim 17 (depends on 1) The flow cell according to claim 1, wherein the exterior surface the freestanding tube has a shape selected from the group consisting of: a rectangle, a circle, a hexagon, a polygon with rounded edges, and a shape of two parallel linear sections connected by two opposing curved sections. ### Claim 18 (depends on 1) The flow cell according to claim 1, wherein the freestanding tube comprises an inner surface having a shape selected from the group consisting of: a rectangle, a rectangle having rounded edges, a circle, and an oval. ### Claim 19 (depends on 1) The flow cell according to claim 1, comprising a feature selected from the group consisting of: the flow cell comprises a first optical coupler element at least partially integrated in the substrate so as to couple electromagnetic radiation via the first optical coupler element into the fluidic conduit; the flow cell comprises a second optical coupler element at least partially integrated in the substrate so as to couple electromagnetic radiation from the fluidic conduit into the second optical coupler element; and both of the foregoing. ### Claim 20 (depends on 1) The flow cell according to claim 1, comprising an electromagnetic radiation source adapted for generating an electromagnetic radiation beam and for coupling the electromagnetic radiation beam into the fluidic conduit. ### Claim 21 (depends on 20) The flow cell according to claim 20, comprising a feature selected from the group consisting of: the electromagnetic radiation source is configured for generating an optical light beam or an ultraviolet beam; the flow cell comprises an electromagnetic radiation detector configured for detecting the electromagnetic radiation beam after propagation through the fluidic conduit; the flow cell comprises an electromagnetic radiation detector configured for detecting the electromagnetic radiation beam after propagation through the fluidic conduit wherein the electromagnetic radiation detector comprises an optical light detector or an ultraviolet radiation detector; and a combination of two or more of the foregoing. ### Claim 22 (depends on 1) The flow cell according to claim 1, a feature selected from the group consisting of: the material of the freestanding tube is optically transparent; the flow cell is configured to conduct a fluidic sample with a high pressure; the flow cell is configured to conduct a fluidic sample with a pressure of at least 50 bar; the flow cell is configured to conduct a fluidic sample with a pressure of at least 100 bar; the flow cell is configured to conduct a liquid sample; the flow cell is configured as a microfluidic flow cell; the flow cell is configured as a nanofluidic flow cell; and a combination of two or more of the foregoing. ### Claim 23 (depends on 1) A fluidic device for measuring a fluidic sample, the fluidic device comprising: a fluid separating device configured for separating the fluidic sample; and a flow cell according to claim 1 in fluid communication with the fluid separating device and configured for receiving the separated fluidic sample from the fluid separating device. ### Claim 24 (depends on 23) The fluidic device according to claim 23, wherein the fluid separating device is integrated in a chip. ### Claim 25 (depends on 24) The fluidic device according to claim 24, wherein the chip comprises a plurality of bonded sheets being patterned so as to form a fluidic conduit for conducting the fluidic sample. ### Claim 26 (depends on 23) The fluidic device according to claim 23, wherein a fluidic conduit of the fluid separating device is configured for conducting the fluidic sample, and is brought in fluid communication with the fluidic conduit of the freestanding tube via a hole-to hole coupling. ### Claim 27 (depends on 26) The fluidic device according to claim 26, wherein the fluid separating device and the flow cell are each formed as planar structures connected to one another at main surfaces of the fluid separating device and the flow cell so as to provide the hole-to-hole coupling at the connected main surfaces. ### Claim 28 (depends on 23) The fluidic device according to claim 23, comprising a feature selected from the group consisting of: the fluid separating device is configured for retaining the fluidic sample being a part of a mobile phase and for allowing other components of the mobile phase to pass the fluid separating device; the fluid separating device comprises a chromatographic column for separating components of the fluidic sample; at least a part of the fluid separating device is filled with a fluid separating material; at least a part of the fluid separating device is filled with a fluid separating material, wherein the fluid separating material comprises beads having a size in the range of 1 μm to 10 μm; at least a part of the fluid separating device is filled with a fluid separating material, wherein the fluid separating material comprises beads having pores having a size in the range of 50 Å to 300 Å; the flow cell is arranged downstream of the fluid separating device; the fluid separating device comprises a microstructured body and porous material covering at least a portion of a surface of the microstructured body; the fluidic device is configured as a fluid separation system for separating compounds of the fluidic sample; the fluidic device is configured to analyze at least one physical, chemical and/or biological parameter of at least one compound of the fluidic sample; the fluidic device comprises a device selected from the group consisting of: a sensor device, a test device for testing a device under test or a substance, a device for chemical, biological and/or pharmaceutical analysis, a capillary electrophoresis device, a liquid chromatography device, and an HPLC device, a gas chromatography device, and a gel electrophoresis device. ### Claim 29 A method of manufacturing a flow cell by micromachining, the method comprising: providing a substrate; integrally forming, from material of the substrate, a freestanding tube such that the freestanding tube is surrounded by a gas atmosphere; and delimiting a fluidic conduit in the freestanding tube, wherein the freestanding tube comprises a section comprising a first end and a second end, and the section is configured for receiving electromagnetic radiation at the first end, and for emitting at the second end electromagnetic radiation having propagated through the fluidic conduit, and wherein the electromagnetic radiation coupled into the fluidic conduit undergoes total internal reflection at a boundary between an exterior surface of the freestanding tube and the surrounding gas atmosphere. ### Claim 30 (depends on 29) The method according to claim 29, wherein the method further comprises: providing a first substrate body and a second substrate body; forming a groove in each of the first substrate body and the second substrate body; bonding the first substrate body to the second substrate body with correspondingly aligned grooves so as to form the fluidic conduit by the aligned grooves and so as to form the substrate by the bonded substrate bodies. ### Claim 31 (depends on 30) The method according to claim 30, wherein the method further comprises forming a trench in the substrate by removing material of the substrate in such a way that the freestanding tube is constituted by non-removed material of the substrate. ### Claim 32 (depends on 29) The method according to claim 29, wherein the method further comprises forming two fluidic channels within the substrate and each being fluidically coupled to a respective end of the freestanding tube. ### Claim 33 (depends on 32) The method according to claim 32, wherein the method further comprises forming spatially extended end sections of the two fluidic channels at positions at which the fluidic channels extend out of the substrate.