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WO2025140846A1 - Biocapteur comprenant une tranche de capteur présentant des évidements, gravés côté arrière, complémentaires d'évidements gravés côté avant d'une tranche microfluidique - Google Patents

Biocapteur comprenant une tranche de capteur présentant des évidements, gravés côté arrière, complémentaires d'évidements gravés côté avant d'une tranche microfluidique Download PDF

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Publication number
WO2025140846A1
WO2025140846A1 PCT/EP2024/085395 EP2024085395W WO2025140846A1 WO 2025140846 A1 WO2025140846 A1 WO 2025140846A1 EP 2024085395 W EP2024085395 W EP 2024085395W WO 2025140846 A1 WO2025140846 A1 WO 2025140846A1
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WO
WIPO (PCT)
Prior art keywords
wafer
biosensor
microfluidic
sensor
recesses
Prior art date
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Pending
Application number
PCT/EP2024/085395
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English (en)
Inventor
Patrick Steglich
Martin Paul
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IHP GmbH
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IHP GmbH
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Filing date
Publication date
Priority claimed from EP24178430.5A external-priority patent/EP4579216A1/fr
Application filed by IHP GmbH filed Critical IHP GmbH
Publication of WO2025140846A1 publication Critical patent/WO2025140846A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures 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
    • B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures 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 characterised by the manufacture of the container or its components
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures 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
    • B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures 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 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0636—Integrated biosensor, microarrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0645—Electrodes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0887—Laminated structure
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions
    • G01N2021/0346—Capillary cells; Microcells

Definitions

  • Chip-integrated biosensors typically have a functionalized biosensor surface associated with a physical sensor device such as interferometers or resonators, which may be realized in a silicon-based photonic integrated circuit (PIC), or electronic sensors.
  • Chip-integrated sensors are generally resistant to electromagnetic interference, exhibit a high sensitivity and a low detection limit, while providing a small footprint, and allow labeled as well as label-free sensing, and also multiplexing of several analytes at the same time.
  • PIC photonic integrated circuit
  • Surface functionalization of the biosensor surface equips a substrate having standard bulk material properties, for instance a silicon substrate formed by a wafer, with specific chemical functional groups on one of its substrate surfaces. Surface functionalization typically involves a material deposition on the substrate.
  • the microfluidic wafer has a second lateral extension, a front side and a back side, the front side comprising integrated microfluidic channel-section recesses that
  • microfluidic wafers are formed and arranged on the front side of the microfluidic wafer in a second pattern that is complementary to the first pattern; wherein sensor wafer and the microfluidic wafer are combined back-surface-to-front- surface in a fluid-tight manner and positioned relative to each other such that given micro- fluidic-channel sections on the microfluidic wafer overlap with respective pairs of biosensor recesses on the sensor wafer and have a lateral extension that establishes a microfluidic interconnection between the respective pairs of biosensor recesses via the microfluidicchannel sections.
  • a microfluidic wafer with microstructures in the form of channel-section recesses on its front side is applied to a back side of the sensor wafer.
  • the sensor wafer is preferably a wafer used in the semiconductor industry for the fabrication of integrated electronic circuit.
  • the sensor wafer may be a silicon wafer or a silicon-on-insulator (SOI) wafer.
  • the biosensor recesses are provided on the back side of the sensor wafer, exposing surface sections of the semiconductor material of the sensor wafer in the biosensor recesses, in particular silicon, as a biosensor surface.
  • biosensor wafer arrangement With the microfluidic wafer that the biosensor surfaces in the recesses on the sensor wafer become fluidically connected with each other and accessible via microfluidic channels for a microfluidic supply of a fluid that provides the functionalization of the biosensor surface in the fabrication process.
  • the biosensor wafer arrangement also allows performing a chemical cleaning step of the biosensor surface before the functionalization, e.g. by etching with HF or KOH or with a plasma, e.g. Ozone, using the same microfluidic access.
  • the biosensor surface may comprise a chemical compound that adheres to the biosensor surface and has a functional group suitable for capturing one or more types of biochemical or biological particles.
  • the chemical compound may for instance be one or more of an amine, an epoxide, a thiol, a carboxy-group, and polyethylene glycol.
  • the wafer arrangement may also be provided for sale without such chemical functionalization of the biosensor surfaces, in order to allow industrial or research customers applying their own desired functionalization of the biosensor surfaces according to the needs of their particular application case, using the microfluidic structure established by the biosensor wafer arrangement.
  • the biosensor surface may be provided coated with an adhesion agent for promoting the chemical functionalization with a chemical compound that is to be provided to the biosensor surface and adhere to the biosensor surface for capturing one or more types of biochemical or biological particles in operation of a biosensor to be fabricated from the biosensor wafer arrangement.
  • the biosensor surface may be silanized. Silaniza- tion thus provides an adherence agent to the silicon surface with functional groups such as amines, epoxides, thiols, polyethylene glycol, etc..
  • This biosensor wafer arrangement thus established may form an either tight or detachable combination.
  • the sensor wafer and the microfluidic wafer are combined by a mechanically detachable connection, for allowing maintaining their combination only temporarily. This allows reusing the microfluidic wafer in the processing of a plurality of sensor wafers.
  • the surface of the microfluidic wafer may be covered with an inert thin sealing film or adhesive film, e.g. PDMS (polydimethylsiloxane), polyurethane, or the like.
  • the microfluidic substrate may be compared with a stamp.
  • the microfluidic substrate may in particular be a plate made of plastic or metal is provided with the channel-section recesses and any required further microstructures, and covered with an inert thin sealing film or adhesive film, as mentioned, and then applied to the back of the sensor wafer.
  • the sensor wafer and the microfluidic wafer are combined by a mechanically tight connection, for permanently maintaining their combination.
  • the integrated biosensor recesses and the microfluidic channel sections may be partitioned into a plurality of groups that are distributed across the wafer.
  • the microfluidic wafer may comprise, extending vertically from the front side to the back side of the microfluidic wafer, a fluid input opening and a fluid output opening. This allows implementing an input and output of fluid for surface functionalization from the backside of the sensor wafer, which helps avoiding contamination or required protective coating of the any electronic components the front side of the sensor wafer.
  • fluidic inlets and outlets are provided which bring any desired fluidic substances in direct contact with the biosensor surface, via fluidic channels established only with the wafer arrangement.
  • the design and arrangement of the fluidic microstructures for the groups i.e., the biosensor recesses and the fluidic-channel sections associated with the groups, is not necessarily, but preferably symmetrical to enable a uniformly distributed supply of fluid for coating the biosensor surface.
  • the microfluidic wafer may comprise on its front surface a sealing film which is chemically inert, for sealing an interface between the back surface of the sensor wafer and the front surface of the microfluidic wafer and limiting flow of fluid to the respective recesses.
  • a sealing film which is chemically inert, for sealing an interface between the back surface of the sensor wafer and the front surface of the microfluidic wafer and limiting flow of fluid to the respective recesses.
  • suitable materials for the sealing film are Polydimethylsiloxane (PDMS) and Polyurethane.
  • the microfluidic wafer of the biosensor wafer arrangement may be some embodiments made of a transparent material, for allowing an optical inspection of fluid transport.
  • the particular structure of the sensor wafer in biosensor wafer arrangement of the present invention provides components (i.e., electronic, optical, optoelectronic or photonic devices) on the front side of the sensor wafer.
  • components i.e., electronic, optical, optoelectronic or photonic devices
  • This allows providing the biosensor surfaces on the back side of the wafer connected to sensing devices on the sensor wafer that are configured, in operation of a biosensor to be fabricated from the wafer arrangement, to detect changes in a physical quantity of the biosensor surface in response to its capturing of the one or more types of biochemical or biological particles, and to provide an electrical signal indicative thereof to the one or more of the components integrated on the front side of the sensor wafer.
  • the physical quantity can be any optical or electrical quantity that is indicative of the presence of a captured particle under test on the functionalized biosensor surface.
  • the front side of the wafer can also be used for electrical or optical contacts and for process control.
  • a second aspect of the present invention is a biosensor chip that is cut from a biosensor wafer arrangement with a suitable functionalization of the biosensor surface in place.
  • a third aspect of the present invention is biosensor wafer kit for fabricating a biosensor wafer arrangement according to any of the described embodiments of the first aspect of the invention, or a biosensor of the second invention.
  • the wafer kit is an intermediate product in the fabrication of biosensor chips and provides a commercial customer specializing in the chemical functionalization of the biosensor surface a corresponding set of wafers for further processing.
  • the wafer kit of the third aspect comprises
  • each of the sensor wafers has a first lateral extension, a front side and a back side, the front side comprising monolithically integrated electronic circuit components, and the back side comprising integrated biosensor recesses that
  • each of the microfluidic wafers has a second lateral extension, a front side and a back side, the front side comprising integrated microfluidic channel-section recesses that
  • microfluidic-channel sections are formed and arranged in a second pattern that is complementary to the first pattern when the sensor wafer and the microfluidic wafer are combined back-surface-to- front-surface and positioned relative to each other such that given microfluidic-channel sections on the microfluidic wafer overlap with respective pairs of biosensor recesses on the sensor wafer and have a lateral extension that establishes a microfluidic interconnection between the respective pairs of biosensor recesses via the microfluidic-channel sections.
  • the wafer kit may comprise a plurality of the sensor wafers and a number of the microfluidic wafers that is smaller than the number of sensor wafers, for multiple re-use of any given microfluidic wafer in the fabrication of biosensor wafer arrangements using a detachable combination between the sensor wafer and the microfluidic wafer.
  • a fourth aspect of the present invention is formed by a method for fabricating a biosensor wafer arrangement according to the first aspect of the invention.
  • the method comprises: providing a wafer kit according to the third aspect of the invention; selecting one sensor wafer and one microfluidic wafer; and positioning relative to each other and combining the sensor wafer and the microfluidic wafer back-surface-to-front-surface such that given microfluidic-channel sections on the microfluidic wafer overlap with respective pairs of biosensor recesses on the sensor wafer and have a lateral extension that establishes a microfluidic interconnection between the respective pairs of biosensor recesses via the microfluidic-channel sections.
  • the positioning is done, whether temporarily or permanently, by a device for pressing the microfluidic wafer and sensor wafer together after a fine adjustment of their relative orientation and position with respect to each other.
  • a device for pressing the microfluidic wafer and sensor wafer together after a fine adjustment of their relative orientation and position with respect to each other.
  • one or more marks on the wafer edge of the sensor wafer and the microfluidic wafer may be used.
  • silicon or SOI wafers used in the industry have a notch providing orientation assistance in the positioning process.
  • the method suitably further comprises providing and conducting to the biosensor surface of the biosensor recesses, through the input opening on the microfluidic wafer and via the microfluidic interconnections between the respective pairs of biosensor recesses established by the microfluidic-channel sections, a functional fluid comprising the chemical compound for chemical functionalization, for adhering to the biosensor surfaces.
  • a fluid pump may be used to apply the fluid from a fluid reservoir, using either overpressure on the input side of the microfluidic wafer or under pressure on the output side of the microfluidic wafer.
  • the method may further comprise, prior to providing the functional fluid, providing and conducting to the biosensor surface of the biosensor recesses, through the input opening on the microfluidic wafer and via the microfluidic interconnections between the respective pairs of biosensor recesses established by the microfluidic-channel sections, a cleaning fluid comprising a cleaning agent for cleaning the biosensor surfaces.
  • a fifth aspect of the present invention is a method for fabricating a biosensor chip.
  • the method comprises
  • Fig. 1 shows a plan view of an exemplary layout of a group, here referred to as test field, of fluidically mutually isolated integrated biosensor recesses, here referred to as LBE (local backside etching) windows, to be provided on a back side of an exemplary sensor wafer;
  • LBE local backside etching
  • Fig. 2 shows a plan view of a back side of an exemplary sensor wafer partitioned into groups of fluidically mutually isolated integrated biosensor recesses as in Fig. 1 , pertaining to an embodiment of the invention
  • Fig. 3 shows a schematic cross-sectional view of the wafer of Fig. 2 along a central horizontal line Ill-Ill in Fig. 2;
  • Fig. 5 shows a plan view of a front side of an exemplary microfluidic wafer partitioned into groups of fluidically mutually isolated channel-section recesses as in Figs. 4A to 4C, pertaining to an embodiment of the invention
  • Figs. 1 to 3 in parallel to describe an exemplary a sensor wafer 200 for use in a biosensor wafer arrangement, which comprises the sensor wafer and a microfluidic wafer (cf. Figs. 4 to 6).
  • Fig. 1 is a plan view of an exemplary layout of a group, here referred to as test field 100, of fluidically mutually isolated integrated biosensor recesses 102, that may also be referred to as LBE (local backside etching) windows, to be provided on a back side BS of an exemplary sensor wafer 200.
  • test field 100 of fluidically mutually isolated integrated biosensor recesses 102, that may also be referred to as LBE (local backside etching) windows, to be provided on a back side BS of an exemplary sensor wafer 200.
  • LBE local backside etching
  • Fig. 3 is a schematic cross-sectional view of the wafer 200 of Fig. 2 along a central horizontal line Ill-Ill shown in Fig. 2. The illustration of Fig. 3 is aligned with that of Fig. 2 in terms of the lateral extension of the sensor wafer 200.
  • test fields 100 cover the entire sensor wafer. Some of the test fields that are arranged on the edge of the sensor wafer 200, such as the test field 104, have a different pattern of arrangement of their LBE windows 102. For this reason, they may be excluded from use in the formation of a biosensor. However, depending on the application they may be used for special purposes differing from those of the test field 100.
  • the biosensor recesses 102 are provided on the back side BS of the sensor wafer 200 to expose surface sections of the semiconductor material of the sensor wafer in the biosensor recesses, in particular silicon, as a biosensor surface.
  • the biosensor wafer arrangement cf. Fig. 7 with the microfluidic wafer (cf. Figs 4 to 6) that the surfaces in the biosensor recesses 102 on the sensor wafer 200 become fluidically connected with each other and thus accessible via microfluidic channels for a microfluidic supply of a fluid that provides a functionalization of the biosensor surface in the fabrication process.
  • the biosensor wafer arrangement also allows performing a chemical cleaning step of the biosensor surface before the functionalization, e.g. by etching with HF or KOH or with a plasma, e.g. Ozone, using the same microfluidic access.
  • Figs. 4 to 6 in parallel to describe an exemplary a microfluidic wafer 500 for use in a biosensor wafer arrangement, which comprises the sensor wafer 200 of Figs. 1 to 3 and the microfluidic wafer.
  • Figs. 4A to 4C show a plan view and two schematic cross-sectional views of a group 400 of fluidically mutually isolated channel-section recesses 402 (also referred to as channels or connector structures), and a fluid distributor channel section 404 (also referred to as reagent distributor channel) with an input hole 406, and a fluid collector channel section 408 with an output hole 410, to be provided in an elevated area 412 on a front side FS of an exemplary microfluidic wafer 500.
  • the wafer 500 may also be referred to as a stamp wafer.
  • a plan view of the front side FS of the exemplary microfluidic wafer 500 is shown in Fig. 5.
  • Figs 6 shows a cross-sectional view of the wafer 500 of Fig. 5 along a central horizontal dashed line VI-VI indicated in Fig. 5. The illustration of Fig. 6 is aligned with that of Fig. 5 in terms of the lateral extension of the microfluidic wafer 500.
  • microfluidic sensor arrangement 800 formed from the sensor wafer 200 and the microfluidic wafer 500 and refers to Figs. 7 to 10 in parallel.
  • FIG. 8 is a plan overlay view of the biosensor wafer arrangement 800 according, with a combination of the microfluidic wafer 500 partitioned into groups 400 of fluidically mutually isolated channel-section recesses 402 on the front side of the microfluidic wafer 500 and complementary groups 100 of fluidically mutually isolated biosensor recesses 102 on a backside of a sensor wafer 200.
  • their complementary arrangement on the wafer level establishes a microfluidic interconnection between the respective pairs of biosensor recesses via the microfluidic-channel sections within a respective group in a biosensor wafer arrangement.
  • Figs. 9 and 10 show schematic cross-sectional views of the biosensor wafer arrangement 800 of Fig. 8 along central horizontal and vertical dashed lines IX-IX and X-X in Fig. 8.
  • the overlay view of Fig. 8 illustrates the effect of an arrangement of the sensor wafer 200 and the microfluidic wafer 500 in a fluid-tight back-surface-to-front-surface combination.
  • the two wafers are precisely positioned relative to each other such that given microfluidicchannel sections 402 on the microfluidic wafer 500 overlap with respective pairs of biosensor recesses 102 on the sensor wafer 200 and have a lateral extension that establishes a microfluidic interconnection between the respective pairs of biosensor recesses 102 via the microfluidic-channel sections 402.
  • the microfluidic wafer 500 with microstructures in the form of channel-section recesses 402 on its front side FS is applied to a back side BS of the sensor wafer 200 to form the biosensor wafer arrangement 800.
  • the complementary arrangement of the pre-fabricated structures on the wafers establishes a microfluidic interconnection between the respective pairs of biosensor recesses 102 via the microfluidic-channel sections 402. This enables a subsequent processing of the biosensor wafer arrangement, in which the biosensor surface may be provided with a chemical compound that adheres to the biosensor surface of the biosensor recesses 102 and has a functional group suitable for capturing one or more types of biochemical or biological particles.
  • the chemical compound may for instance be one or more of an amine, an epoxide, a thiol, a carboxy-group, and polyethylene glycol.
  • the microfluidic wafer 500 can be removed after this fabrication step. In other applications, the microfluidic wafer 500 remains applied to the sensor wafer 200 permanently.
  • the biosensor wafer 200 or the arrangement of the biosensor wafer and the microfluidic wafer can subsequently be divided into individual biosensor chips comprising one or more of the groups or test fields 100.
  • biosensor wafer arrangement instead of using a single microfluidic wafer 500 as illustrated in Figs. 8 to 10, several smaller microfluidic wafers 500 forming small sub-stamps and covering different sections of the sensor wafer 200 can be used in the fabrication process of a biosensor wafer. The biosensor wafer can then be subsequently divided into individual biosensor chips.
  • Figs 8 to 10 thus also illustrate a biosensor wafer kit that may be provided by a wafer manufacturer to a biosensor manufacturer as an intermediate product for completing the fabrication of a biosensor wafer or a biosensor wafer arrangement as described.
  • the biosensor wafer kit comprises one or more of the sensor wafers 200 and one or more of the microfluidic wafers 500.
  • microfluidic wafer (stamp) 500 can be fabricated according to different production methods, as described in the following: First Option:
  • a polished, stable substrate made of polymer, glass, ceramic or metal is provided with fine, symmetrical channels of shallow depth (>10 pm, ⁇ 1000 pm) by precision machining, e.g. laser ablation, micro-CNC milling or electrochemical machining (ECM).
  • the substrate can also be drilled to allow reagents to be pumped or sucked in and out of the stamp via the rear side.
  • the surface of the stamp 500 that comes into contact with the sensor wafer 200 is coated with an elastic substance, e.g. silicone (Dow Sylguard 184), thermoplastic polyurethane (TPU) or fluororubber (FKM) thinly coated (1-500 pm), e.g. with spin coating or sprayed on.
  • silicone Dow Sylguard 184
  • TPU thermoplastic polyurethane
  • FKM fluororubber
  • a polished, stable substrate made of polymer, glass, ceramic or metal is coated with a thin layer of elastic, light-sensitive photoresist, e.g. by spin coating.
  • the resist is then selectively exposed with a laser (i.e. "maskless") or with a photo mask, so that the exposed material can then either be removed with solvent (positive) or the unexposed material is removed (negative) and a structure with fine, symmetrical channels is obtained. Holes for fluid input and output can then be drilled to contact the structures. Alternatively, an impression of the exposed microstructures can be made from elastic polymer and bonded to a stable support to obtain the stamp.
  • Additive manufacturing processes such as stereolithography (SLA) or two-photon polymerization (TPP) can be used to grow thin (1-500 pm) microstructures made of elastic material on stable substrates made of polymer, glass, ceramic or metal. Holes can then be drilled to contact the structures.
  • SLA stereolithography
  • TPP two-photon polymerization
  • microfluidic wafer 500 in the fabrication process of a biosensor wafer 200 with biosensor recesses:
  • An LBE process creates ordered cavities in the test fields 100 of the sensor wafer 200, which are delimited by a thin membrane consisting of the front end of line (FEOL) and the back end of line (BEOL) as well as by the surrounding bulk silicon of the wafer.
  • the stamp wafer 500 also has cavities, in particular microfluidic channels 402, which are arranged complementarily to the biosensor recesses 102 on the sensor wafer 200 when the stamp wafer 500 is correctly positioned relative to the sensor wafer 200. This leads to the (temporary or permanent, as desired) formation of microfluidic channels when the stamp (microfluidic wafer) is precisely positioned on the back of the wafer.
  • the stamp In addition to the LBE connection cavities, the stamp must also contain input and output transport channels for reagents.
  • These channels may not be arranged exclusively symmetrically in order to generate the same counterpressures through the same path lengths of the channels to enable a homogeneous coating, in particular with layer containing a chemical compound that adheres to the biosensor surface and has a functional group suitable for capturing one or more types of biochemical or biological particles.
  • the stamp For the sealing of stamp and wafer, the stamp must have a planar surface with low roughness, which consists of a flexible material that is inert for the reagents used, such as PDMS or fluoropolymers.
  • a biosensor wafer arrangement comprises a sensor wafer and a microfluidic wafer.
  • the sensor wafer comprises integrated components. On its opposite back side, it has integrated biosensor recesses.
  • the biosensor recesses are fluidically isolated from each other and have a biosensor surface connected with one or more components on the front side for sensor signal communication through the sensor wafer.
  • the biosensor recesses are provided in a first pattern.
  • the microfluidic wafer on its front side, comprises microfluidic channel-section recesses that are fluidically isolated from each other, and are provided in a second pattern which is complementary to the first pattern.
  • the sensor wafer and the microfluidic wafer may be combined back-to-front and in a fluid-tight manner, and positioned relative to each other such that microfluidic-channel sections on the microfluidic wafer overlap with pairs of biosensor recesses on the sensor wafer to establish a microfluidic interconnection between the pairs of biosensor recesses via the microfluidic-channel sections.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

Un agencement de tranches de biocapteur comprend une tranche de capteur et une tranche microfluidique. La tranche de capteur comprend des composants intégrés. Sur son côté arrière opposé, elle comporte des évidements de biocapteur intégrés. Les évidements de biocapteur sont isolés fluidiquement les uns des autres et comportent une surface de biocapteur connectée à des composants sur le côté avant pour permettre une communication de signaux de capteur à travers la tranche de capteur. Les évidements de biocapteur sont formés selon un premier motif. La tranche microfluidique, sur son côté avant, comprend des évidements de sections de canaux microfluidiques qui sont isolés fluidiquement les uns des autres, et sont disposés selon un deuxième motif complémentaire du premier motif. La tranche de capteur et la tranche microfluidique peuvent être combinées dos à devant et de façon étanche aux fluides, et positionnées l'une par rapport à l'autre de sorte que des sections de canaux microfluidiques sur la tranche microfluidique se chevauchent avec des paires d'évidements de biocapteur sur la tranche de capteur pour établir une interconnexion microfluidique entre les paires d'évidements de biocapteur par l'intermédiaire des sections de canaux microfluidiques.
PCT/EP2024/085395 2023-12-28 2024-12-10 Biocapteur comprenant une tranche de capteur présentant des évidements, gravés côté arrière, complémentaires d'évidements gravés côté avant d'une tranche microfluidique Pending WO2025140846A1 (fr)

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EP24178430.5A EP4579216A1 (fr) 2023-12-28 2024-05-28 Biocapteur comprenant un wafer capteur avec des évidages gravés à l'arrière qui sont complémentaires à des évidages gravés sur le côté avant d'un wafer microfluidique
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WO2001089788A2 (fr) * 2000-05-25 2001-11-29 President And Fellows Of Harvard College Formation de motifs sur des surfaces, au moyen de tampons microfluidiques comprenant des reseaux de canaux disposes en trois dimensions
WO2005107938A2 (fr) * 2004-05-02 2005-11-17 Fluidigm Corporation Dispositif de réaction thermique et méthode d'utilisation de semblable
US20180221878A1 (en) * 2015-10-09 2018-08-09 Sysmex Corporation Specimen treatment chip, specimen treatment apparatus, and specimen treatment method

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WO2001089788A2 (fr) * 2000-05-25 2001-11-29 President And Fellows Of Harvard College Formation de motifs sur des surfaces, au moyen de tampons microfluidiques comprenant des reseaux de canaux disposes en trois dimensions
WO2005107938A2 (fr) * 2004-05-02 2005-11-17 Fluidigm Corporation Dispositif de réaction thermique et méthode d'utilisation de semblable
US20180221878A1 (en) * 2015-10-09 2018-08-09 Sysmex Corporation Specimen treatment chip, specimen treatment apparatus, and specimen treatment method

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