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WO2025123049A1 - Résonance plasmonique de surface avec manipulation microfluidique mécanique - Google Patents

Résonance plasmonique de surface avec manipulation microfluidique mécanique Download PDF

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Publication number
WO2025123049A1
WO2025123049A1 PCT/US2024/059240 US2024059240W WO2025123049A1 WO 2025123049 A1 WO2025123049 A1 WO 2025123049A1 US 2024059240 W US2024059240 W US 2024059240W WO 2025123049 A1 WO2025123049 A1 WO 2025123049A1
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WO
WIPO (PCT)
Prior art keywords
sheet
metal
gap
cartridge
microfluidics
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Pending
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PCT/US2024/059240
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English (en)
Inventor
Mais J. Jebrail
Rohit LAL
Foteini CHRISTODOULOU
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Integra Biosciences AG
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Integra Biosciences AG
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Publication of WO2025123049A1 publication Critical patent/WO2025123049A1/fr
Pending legal-status Critical Current
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    • 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
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/55—Specular reflectivity
    • G01N21/552—Attenuated total reflection
    • G01N21/553—Attenuated total reflection and using surface plasmons
    • 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
    • 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
    • B01L3/50273—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 means or forces applied to move the fluids
    • 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
    • B01L3/502769—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 multiphase flow arrangements
    • B01L3/502784—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 multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
    • B01L3/502792—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 multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics for moving individual droplets on a plate, e.g. by locally altering surface tension
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366—Apparatus specially adapted for solid-phase testing
    • G01N33/54373—Apparatus specially adapted for solid-phase testing involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/566—Immunoassay; Biospecific binding assay; Materials therefor using specific carrier or receptor proteins as ligand binding reagents where possible specific carrier or receptor proteins are classified with their target compounds
    • 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
    • B01L2300/12—Specific details about materials
    • B01L2300/123—Flexible; Elastomeric
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • B01L2400/0427—Electrowetting
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/06—Investigating concentration of particle suspensions
    • G01N15/0606—Investigating concentration of particle suspensions by collecting particles on a support
    • G01N15/0612—Optical scan of the deposits

Definitions

  • Microfluidics deal with very small volumes of fluids, down to femtoliters (fL) which is a quadrillionth of a liter. Fluids behave very differently on the micrometric scale than they do in everyday life: these unique features are the key for new scientific experiments and innovations.
  • Microfluidics devices may include micro-channels and require microminiaturized devices containing chambers and tunnels through which fluids flow or are confined.
  • DMF digital microfluidics
  • reagents no pumps, valves, or tubing required
  • facile handling of both solids and liquids no channels to clog
  • compatibility with even troublesome reagents e.g., organic solvents, corrosive chemicals
  • hydrophobic surfaces typically Teflon-coated
  • conventional DMF devices use relatively large electric fields selectively applied to an array of electrodes to manipulate the droplets. The generation and control of these electric fields requires specialized and complex circuitry capable of withstanding the relative high voltages.
  • SPR Surface plasmon resonance
  • a SPR microfluidics device may offer improved SPR analysis by using precise sample control and reduced sample consumption.
  • an SPR microfluidics device can include a mechanically actuated microfluidics system that further includes a light source, a light detector, and a thin metal plate.
  • the thin metal plate may reflect light from the light source to the light detector. Analysis of the reflected light may determine the presence of any feasible analyte in contract with the metal plate. Preparation of the metal plate or metal layers may be performed with the mechanically actuated microfluidics system.
  • the mechanically actuated microfluidics system may include a cartridge.
  • the cartridge may include two hydrophobic or oleophobic sheets and/or coatings applied to sheets. At least one sheet may be flexible and responsive to forces, such as compressive forces which can be applied to the cartridge to manipulate (move) liquid droplets.
  • the cartridge may also include multiple sensor regions (areas) that include a thin metal layer or plate. A sample containing an analyte may be manipulated into the sensor regions where SPR analysis can take place. The multiple sensor regions may advantageously enable parallel SPR analysis for multiple analytes.
  • any of the methods described herein may perform surface plasmon analysis with a microfluidics device.
  • the methods may include introducing a ligand into a gap formed between an elastically deformable first sheet and a second sheet, wherein the first sheet is disposed a predetermined distance from the second sheet to form the gap, moving the ligand into a sensor region of the microfluidics device, wherein the moving includes translating a mechanical force applicator along an outer surface of a first sheet to form a locally reduced gap within the gap, wherein the ligand follows the mechanical force applicator, moving a sample droplet into the sensor region with the mechanical force applicator, illuminating the sensor region with a light source, illuminating the sensor region with a light source, and determining a presence of an analyte within the sample based on the detected light.
  • the ligands may be any feasible ligand that can bond with any feasible analyte.
  • the ligand may be immobilized with respect to the sensor region.
  • an analyte can bond with a ligand and affect how light is reflected from the sensor region.
  • Any of the methods described herein can include washing the sensor region with ethanol prior to introducing the ligand. Ethanol may help clean the sensor region.
  • any of the methods described herein can include immobilizing the ligand to a thin metal sheet in the sensor region.
  • the thin metal sheet (sometimes referred to as a thin metal layer) may be used to immobilize a ligand and reflect light. For example, light from the light source directed towards the thin metal sheet may be reflected toward the light detector.
  • the thin metal sheet may be disposed within the gap.
  • the thin metal sheet may be composed substantially of gold, silver, copper, platinum, or aluminum. Still further, the thin metal sheet may be approximately between 30 to 70 nanometers in thickness. Any of the methods described herein may further include activating at least one carboxyl group on the thin metal sheet prior to moving the ligand into the sensor region.
  • the ligands may be bonded to the thin metal sheet.
  • the light source may provide at least one of monochromatic, white, or laser light.
  • a surface plasmon resonance device may include a microfluidics cartridge and a controller.
  • the microfluidics cartridge can include an elastically deformable first sheet, a second sheet, wherein the first sheet is disposed a predetermined distance from the second sheet to form a gap, and a thin layer of metal configured to receive a ligand.
  • the controller can include a mechanical force actuator configured to deform the first sheet and reduce the gap and thereby cause fluids to move within the reduced gap, a light source configured to provide light at a predetermined angle to the thin layer of metal, and a light detector configured to detect light from the light source reflected from the thin layer of metal.
  • the thin layer of metal may be disposed within the air gap and on the first sheet.
  • the first sheet may be transparent. A transparent first sheet may allow light to travel through the prism, and reflect off the thin layer of metal to the light detector.
  • the thin layer of metal may include gold, silver, copper, platinum, aluminum, or a combination thereof.
  • the microfluidics cartridge may include a heating element disposed on the second sheet on or near the second sheet opposite the thin layer of metal.
  • the mechanical force actuator is further configured to deform the first sheet except in regions that include the thin layer of metal.
  • the microfluidics cartridge can include a port to receive and convey fluids to the gap.
  • the controller may be configured to determine the presence of an analyte through changes in the light reflected from the thin layer of metal.
  • the microfluidics cartridge may include a prism disposed on the first sheet, opposite the thin layer of metal.
  • the mechanical force actuator may be further configured to avoid the prism.
  • a cartridge for performing microfluidic droplet manipulation and surface plasmon resonance may include an elastically deformable first sheet, a second sheet, wherein the first sheet is disposed a predetermined distance from the second sheet to form a gap therebetween, one or more thin layers of metal configured to receive a ligand, and an input port configured to receive a droplet and introduce the droplet to the gap.
  • the first sheet may be configured to receive a force from a mechanical force actuator to reduce the gap and cause fluids to move within the reduced gap.
  • the one or more thin layers of metal are disposed within the gap.
  • the cartridges may include a plurality of sensor areas where each sensor area includes one of the one or more thin layers of metal.
  • the thin layers of metal may include gold, silver, copper, platinum, aluminum, or a combination thereof.
  • the one or more thin layers of metal may be disposed on the first sheet.
  • the cartridge may further include a prism disposed on the first sheet opposite the thin layers of metal.
  • the cartridge may further include one or more heating elements disposed adjacent to the second sheet opposite the one or more thin layers of metal.
  • the one or more thin layers of metal may be between approximately 30 to 70 nanometers (nm) in thickness.
  • FIGS. 1A-1C show a portion of a microfluidics device configured to manipulate microfluidic droplets via a mechanical actuator.
  • FIG. 2 shows an example surface plasmon resonance microfluidics device.
  • FIGS. 3A-3D shows an example surface plasmon resonance microfluidics system.
  • FIG. 4 shows stages of operation of an example surface plasmon resonance microfluidics system.
  • FIG. 5 is a response graph showing a possible response of a metal sheet to an analyte over time.
  • FIG. 6 shows another example surface plasmon response microfluidics device.
  • FIG. 7 shows a simplified view of an example microfluidics cartridge.
  • FIG. 8 is a simplified block diagram of an example surface plasmon resonance micro fluidics device.
  • FIG. 9 is a flowchart showing an example method for performing surface plasmon resonance analysis with a surface plasmon resonance microfluidics device.
  • FIG. 10 shows a block diagram of a surface plasmon resonance microfluidics device that may be one example of any of the microfluidics devices described herein.
  • a microfluidic apparatus for controlled liquid manipulation may include a two-dimensional (planar) fluidic chamber.
  • the chamber may include a first sheet and a second sheet separated by a gap therebetween.
  • the gap may separate the first and second sheets by any feasible distance.
  • the first and second sheets may be hydrophobic or may include hydrophobic coatings.
  • the first and second sheet are hydrophobic and oleophobic and/or include a hydrophobic and oleophobic coating.
  • Microfluidic droplets may be manipulated through mechanical manipulation that applies forces directly or indirectly to the first sheet or second sheet selectively reducing the gap. This process may sometimes be referred to as mechanical actuation on the surface (MAOS), also described as the use of mechanical compression to change the capillary force.
  • the applied forces which may include compressive forces, may be applied near or adjacent to droplets within the gap. In some aspects, reducing the gap may cause the droplets to move, separate, combine, mix, incubate, or the like.
  • the forces may be applied by a stylus.
  • the stylus may include an electrode and/or a controllable magnet.
  • the microfluidic droplets may be manipulated with a combination of pressure, exerted by the stylus, in conjunction with a voltage provided by the electrode and/or a magnetic field provided by the magnet.
  • SPR analysis may be used to detect the presence of any feasible analyte within various droplets.
  • Conventional SPR analysis may be complex to set up, possibly limiting the use of SPR analysis.
  • Combining MAOS techniques with SPR analysis may make SPR analysis easier to perform and increase the accessibility to more researchers.
  • MO AS In MO AS, discrete droplets containing samples and reagents, typically in the range of pico- to micro-liters, are confined between two hydrophobic surfaces.
  • the top surface is designed to be flexible. When localized compressive forces are applied to this flexible surface, it triggers a capillary action phenomenon on one side of the droplet, allowing for precise manipulation of the droplet's behavior. This manipulation encompasses controlled movement, blending with adjacent droplets, and regulated dispensing from predetermined reservoirs, all of which facilitate meticulous handling for analytical purposes.
  • FIGS. 1A-1C show a portion of a microfluidics device configured to manipulate microfluidic droplets via a mechanical actuator.
  • the microfluidics device of FIGS. 1 A-1C may be in a SPR microfluidics device.
  • the mechanical actuator can selectively apply pressure to deform at least one sheet of a two-sheet microfluidics device and/or cartridge. The pressure can reduce a gap (air gap) between the two sheets and cause the microfluidic droplet to move through capillary action. Examples of such microfluidics devices are described in U.S. patent application Ser. No. 18/062,007 fded on December 5, 2022 and Ser. No. 18/062,011 filed on December 5, 2022 now U.S. Patent No. 11,772,093, all commonly assigned, the disclosures of which are incorporated by reference herein in their entireties.
  • FIG. 1A shows a portion of a microfluidics device 100. Any of the devices described herein may be implemented in part or in whole as a system or any other feasible apparatus.
  • the microfluidics device 100 may include a first sheet 110 and a second sheet 120 separated by a gap 130. In some examples, the gap 130 may generally be filled with air.
  • the microfluidics device 100 may be a cartridge that may be selectively coupled to a control unit or base station. As shown, the first sheet 110 may be a “top” sheet and the second sheet 120 may be a “bottom” sheet. That is, the first sheet 110 may be higher or “above” the second sheet 120. The second sheet 120 may be closer to the ground than the first sheet 110.
  • the second sheet 120 may be above the first sheet 110.
  • the first sheet 110 and the second sheet 120 may form a planar structure that occupies any feasible area.
  • the first sheet 110 and the second sheet 120 are shown in an initial position. In the initial position, the first sheet 110 and the second sheet 120 are relatively parallel to each other separated by a distance associated with and/or determined by the gap 130.
  • Each sheet may include two surfaces.
  • the first sheet 110 may include a first surface 111 and a second surface 112 and the second sheet 120 may include a first surface 121 and a second surface 122.
  • the first surfaces 111 and 121 may be disposed toward the gap 130, while the second surfaces 112 and 122 may be disposed on opposite sides of the first sheet 110 and the second sheet 120, respectively.
  • the second surfaces 121 and 122 may be disposed away from the gap 130.
  • the first surfaces 111 and 121 may be hydrophobic (water repelling).
  • the first and second sheets 110 and 120 (and thus the first surfaces 111 and 121) may be formed from a hydrophobic material.
  • the first surfaces 111 and 121 may be a hydrophobic coating or layer applied upon the first and second sheets 110 and 120, respectively.
  • a droplet 140 may be introduced into the gap 130.
  • the droplet 140 may be introduced in the gap 130 through a port or opening (not shown) on the first sheet 110 and/or the second sheet 120.
  • the droplet 140 may be mechanically manipulated by selectively reducing the gap near the droplet 140.
  • one or more of the sheets 110 and 120 may be flexible. Flexible sheets may deflect in response to one or more forces.
  • the first sheet 110 may be flexible and the second sheet 120 may be rigid or semirigid. Rigid or semi-rigid sheets may resist deflection in response to one or more forces.
  • the second sheet 120 may be flexible and the first sheet 110 may be rigid or semi-rigid.
  • both the first sheet 110 and the second sheet 120 may be flexible.
  • the term flexible may describe any material that may flex, deform, bend, move, or the like.
  • the droplet 140 may have a predetermined volume.
  • the droplet 140 may be a microfluidic droplet having a volume of the droplet 140 may be between 10' 6 and IO 15 liters, although in some examples the volume of the droplet 140 can have any other feasible volume.
  • the gap 130 may be determined, at least in part, by the volume of the droplet 140. In other words, the gap 130 may be chosen or selected such that the droplet 140 (e.g., the volume of the droplet 140) can touch both the first and second sheets 110 and 120.
  • FIG. IB shows another view of the microfluidics device 100.
  • the first sheet 110 may be deflected by a compression force near or adjacent to one side or end of the droplet 140.
  • the compression force may be provided by a mechanical actuator 113.
  • a position of the mechanical actuator 113 (sometimes referred to as a mechanical force actuator) may be controlled by a robotic arm or similar device.
  • the compression force creates a reduced gap 132 between the first sheet 1 10 and the second sheet 1 0 toward the end or side of the droplet 140.
  • the droplet 140 may deform asymmetrically and be drawn toward the reduced gap 132.
  • the droplet movement may be caused by differential capillary action and/or a differential pressure gradient within the droplet 140.
  • the compression force may be provided by any other feasible means.
  • an array of electro-mechanical, mechanical, and/or pneumatic actuators may be disposed next to the first sheet 110 and/or the second sheet 120 to selectively provide a compression force to form the reduced gap 132.
  • the compression force may be provided by a stylus that may contact the first sheet 110 and/or the second sheet 120.
  • the microfluidics device 100 may include one or more optical sensors (not shown).
  • the one or more optical sensors may detect the presence and/or position of the droplet 140. In this manner, data from the optical sensors may be used to assist the application of a compression force near or adjacent to the droplet 140.
  • FIG. 1C shows another view of the microfluidics device 100.
  • the compression force on the first sheet 110 has been removed or reduced and the first sheet 110 and the second sheet 120 have returned to an initial position (as shown in FIG. 1A).
  • the gap 130 may be similar to the gap 130 of FIG 1A.
  • the droplet 140 is shown in a second position having moved in response to the compression force described with respect to FIG. IB.
  • any droplet may be manipulated to any area within the microfluidics device 100 (in some cases, within a cartridge) by reducing the gap near one end of the droplet.
  • This method advantageously avoids the generation and control of high voltages as well as the need for a plurality of electrodes that are associated with conventional microfluidics devices.
  • the compression force described herein may be provided by any feasible source. For example, mechanical levers, balls, rollers, or the like may apply the compression force to at least one of the first or second sheets 110 and 120, respectively.
  • the compression force may be computer or processor controlled.
  • the manipulation of the droplet 140 may be computer and/or processor controlled.
  • the SPR microfluidics device 200 may include a first sheet 210, a second sheet 220, a metal sheet 211, a prism 213, a light source 250, and a light detector 255.
  • Other SPR microfluidics devices may include more or fewer elements.
  • the metal sheet 211 a very thin sheet that may be bonded, deposited, or otherwise attached to either sheet. Tn the example SPR microfluidics device 200, the metal sheet is shown attached to the first sheet 210, however in other examples, the metal sheet 211 may be attached to the second sheet 220. In some examples, the metal sheet 211 may be between 30 to 70 nanometers (nm) in thickness. The other dimensions of the metal sheet 211 may range from 0.05 cm x 0.05 cm to 2 cm x 2 cm. In some other examples, the metal sheet 211 may have any other feasible dimensions. The metal sheet 211 may include gold, silver, copper, platinum, or aluminum. In some examples, the first sheet 210 may be a dielectric.
  • the first sheet 210 may be spaced away from the second sheet 220 such that a gap 214 is formed therebetween.
  • the gap 214 may be filled with air.
  • the metal sheet 211 is disposed within the gap 214.
  • the prism 213 may be positioned opposite the metal sheet 211 with respect to the first sheet 210.
  • the first sheet 210 may be transparent. Therefore, the prism 213 may be outside of the gap 214, disposed on the first sheet 210, and opposite to the metal sheet 211.
  • Ligands may be disposed or deposited on the metal sheet 211. Light from the light source 250 may travel through the prism 213 and reflect toward the light detector 255.
  • light from the light source 250 may strike the metal sheet 211 at a particular angle of incidence such that some photons travel parallel to the surface of the metal sheet 211. Reflected light intensity is monitored through the light detector 255.
  • the ligands 212 which are introduced into the gap 214 and deposited to the metal sheet 211.
  • the reflective index of the metal sheet 211 changes. The change in reflective index causes a change in the light reflected to the light detector 255. In this manner, the presence of analytes within a droplet 240 can be detected by a change in the reflected light.
  • the SPR microfluidics device 200 may be replicated so that cartridge can include multiple SPR microfluidics devices 200.
  • Mechanical actuation may be used to move a microfluidic droplet to a sensor area.
  • compressive forces may be applied to the first sheet 210 and/or the second sheet 220 to move a droplet within the gap 214.
  • the compressive forces may come near, but not be applied to the prism 213.
  • the compressive forces may be applied near the metal sheet 211, but not deform the metal sheet 211 itself. Therefore, the compressive forces may deform the first sheet 210, but not the prism 213 nor the metal sheet 211.
  • compressive forces from a mechanical force actuator may be configured to avoid the prism 213 and/or the metal sheet 211.
  • a sensor area may be defined as a region near, adjacent to, or including the metal sheet 211.
  • compressive forces can advantageously draw droplets into the sensor area without damaging the prism 213 and/or the metal sheet 211.
  • various micro fluidic droplets may be tested for the presence of various analytes with SPR analysis using a SPR microfluidics system.
  • FIG. 3A shows an example SPR microfluidics system 300.
  • the SPR microfluidics system 300 may include a first sheet 310, a second sheet 320 and a metal sheet 311.
  • the first sheet 310 may be an example of the first sheet 210
  • the second sheet 320 may be an example of the second sheet 220
  • the metal sheet 311 may be an example of the metal sheet 211 described with respect to FIG. 2.
  • the SPR microfluidics system 300 may be prepared for SPR with a cleaning process.
  • a cleaning process may include actuating a 25 uL droplet of ethanol over the metal sheet 211 three times, effectively cleansing the metal sheet 311. Subsequently, these cleaned metal sheets 311 (sometimes referred to as sensors) are left to naturally air-dry at room temperature for approximately five minutes.
  • a self-assembled monolayer is formed on the metal sheet 311.
  • the SAM provides a uniform, one molecule thick layer of carboxyl (COOH) functional groups on the surface of the metal sheet 311 (gold sensor).
  • Formation of the SAM may include the use of 11-mercaptoundecanoic acid (MU A) as shown in FIG. 3B.
  • MU A 11-mercaptoundecanoic acid
  • a 25 uL microfluidic droplet of a 1-millimolar (ImM) MUA solution in ethanol is driven (manipulated with a mechanical actuator) over the metal sheet 311.
  • the MUA solution is allowed to interact with the metal sheet 311 over a span of 12 hours.
  • the ethanol may be periodically replenished.
  • Covalent bonding of ligands (IgGs) to the metal sheet 311 may include activating the carboxyl (COOH) groups present on the metal sheets 311. For example, a 25 uL droplet of a freshly prepared mixture (1:1 v/v) of 0.4M ethylene dichloride (EDC) and 0.1M N- Hydroxy succinimide (NHS) may be applied to the metal sheets 311 for a duration of 300 seconds. [0064] Following this activation, a 25 uL droplet of the ligand dissolved in a coupling buffer at a concentration of 150 g/ml. is applied over the activated metal sheets 311, resulting in immobilization of IgGs 340.
  • COOH carboxyl
  • IgGs were covalently immobilized on the surface using an amine coupling strategy as shown in FIGS. 3C and 3D.
  • other coupling strategies such as Streptavidin-Bio tin Coupling, Carboxyl Coupling, Epoxide Coupling, Hydrophobic Interaction, His-Tag Coupling, and Acid/Base Coupling can be used.
  • any remaining activated COOH groups may be blocked by passing a 25 uL droplet of IM ethanolamine (pH 8.5) over the metal sheet 311. The metal sheet 311 is then washed twice with 25 uL of the coupling buffer. At this point, the IgGs 340 are ready to be exposed to any feasible analyte.
  • FIG. 4 shows stages of operation of an example SPR microfluidics system 400.
  • the SPR microfluidics system 400 may include a first sheet 410, a metal sheet 411, a plurality of IgGs 412, a prism 413, a second sheet 420, a light source 450, and a light detector 455.
  • a first stage 470 the SPR microfluidics system 400 has been prepared to detect an analyte.
  • the metal sheet 411 may be prepared as described with respect to FIGS. 3A-3D coupling IgGs 412 to the metal sheet 411.
  • the IgGs 412 are prepared to accept and bond with an analyte.
  • the IgGs described herein can be any feasible IgGs. Some IgGs may only bond with a particular analyte. Thus, the IgGs 412 may be selected to indicate the presence of a specific analyte. In some cases, the SPR microfluidics system 400 may include several different “sensor areas” that include different metal sheets 411. Thus, different sensor areas can be bonded with different IgGs in order to detected different (multiple) analytes.
  • a droplet 480 is moved to the sensor area.
  • the droplet 480 may include an analyte 481.
  • the analytes 481 are attracted to and bond with IgGs 412. As the analytes 481 begin to bond with the IgGs 412, changes in reflected light can be observed by the light detector 455.
  • the droplet 480 may be moved to the sensor area through mechanical manipulation as described with respect to FIG. 1A-1C.
  • a third stage 472 equilibrium may be reached as the association and dissociation rates of the analyte 481 with respect to the IgGs 412 balance.
  • a response of the analyte 481 to the ligand increases (where the response is detected by the light detector 455 through changes in reflected light from the light source 450).
  • a droplet of a running buffer 482 [Inventors: what is the difference between a running buffer (mentioned here) and a coupling buffer (mentioned above in paragraph 0025)? is manipulated over the metal sheet 411 to regenerate the sensor. Regeneration can prepare the metal sheet 411 to sense the analyte 481 in another microfluidic droplet. Analytes 481 may be flushed from the IgGs 412 by the running buffer.
  • FIG. 5 is a response graph showing a possible response of the metal sheet 411/IgGs 412 to an analyte over time with respect to the stages described in FIG. 4.
  • FIG. 6 shows another example SPR microfluidics device 600.
  • the SPR microfluidics device 600 may include a first sheet 610, a second sheet 620, a heating element 621, a metal sheet 611, a prism 613, a light source 650, and a light detector 655.
  • Other SPR microfluidics devices may include more or fewer elements.
  • the SPR microfluidics device 600 may be similar to the SPR microfluidics device 200 of FIG. 2. Thus, the first sheet 610 and the second sheet 620 may form a gap 614 which can receive a droplet 640.
  • Ligands 612 may be bonded to the metal sheet 611 and can receive an analyte 641 that may be present in the droplet 640. Presence of the analyte 641 may affect light reflected by the metal sheet 611 to the light detector 655.
  • the heating element 621 may provide a controllable, localized heat source that may be used before, during, or after SPR analysis.
  • the droplet 640 may be positioned into a sensor area and then heat applied from the heating element 621 as desired to perform or promote any feasible chemical reaction.
  • the heating element 621 may be replaced with a cooling element or a Peltier device. In this manner, localized cooling may also be provided to the droplet 640.
  • the heating element 621 may be attached to a base or controller unit that receives a cartridge that includes the elements of FIG. 6. In this manner, the heating elements be used with any cartridge attached to the base or controller unit.
  • FIG. 7 shows a simplified view of an example microfluidics cartridge 700.
  • the microfluidics cartridge 700 may include input ports 710, sensor regions 720, and output ports 730.
  • FIG. 7 shows a only a first sheet of the microfluids cartridge 700.
  • a second sheet (not shown) may be behind the first sheet.
  • the microfluidics cartridge 700 may include a first sheet, a second sheet, an airgap, one or more prisms, one or more metal sheets, one or more heating elements as described with respect to the SPR microfluidics device 600 of FIG.
  • the microfluidics cartridge 700 may be used for performing microfluidic droplet manipulation and surface plasmon resonance.
  • the microfluidics cartridge 700 can include any number of sensor regions 720.
  • Each sensor region 720 can include a thin layer of metal, disposed within the air gap, and a prism directly opposite to (on the other side of the sheet) the thin layer or metal.
  • the input ports 710 may allow fluids (droplets) to be introduced into the air gap.
  • the output ports 730 may allow fluids to be withdrawn from the air gap.
  • fluids may include any feasible fluid, including any fluids described herein to prepare the metal layer to receive ligands, fluids that include one or more analytes, and cleaning solutions.
  • a plurality of sensor regions may be used to test for the presence of a plurality of analytes.
  • different ligands may be immobilized with respect to the different sensor regions 720, where each ligand may be sensitive to different analytes.
  • the microfluidics cartridge 700 can function as a biosensor array and simultaneously test for the presence of several different analytes.
  • the microfluidics cartridge 700 can advantageously simultaneously monitor the binding kinetics and affinity of multiple molecular interactions in parallel, saving time and resources. This allows the simultaneous screening of various analytes for high-throughput applications.
  • FIG. 8 is a simplified block diagram of an example SPR microfluidics device 800.
  • the SPR microfluidics device 800 may include a controller 810, a microfluidics cartridge 820, and an actuator and sensing unit 830.
  • the microfluidics cartridge 820 can be any cartridge described herein, particularly the microfluidics cartridge 700 of FIG. 7.
  • the controller 810 may be configured to receive one or more microfluidics cartridge 820.
  • the controller 810 which is communicatively coupled to the actuator and sensing unit 830, can control one or more mechanical force actuators (not shown) to reduce an air gap within the microfluidics cartridge and move droplets of liquid within the microfluidics cartridge 820.
  • the controller 810 can cause the actuator and sensing unit 830 to provide liquid to input ports and extract liquid from output ports, such as the input ports 710 and the output ports 730 of FIG. 7.
  • the controller can manipulate ligands and test samples including analytes to any sensing areas of the microfluidic cartridge 820.
  • the actuator and sensing unit 830 can include one or more light sources and light detectors (not shown).
  • the light sources may direct light at a predetermined angle with respect to any sensor areas of the microfluidics cartridge 820.
  • the light detector may detect light reflected from the sensor areas.
  • the controller 810 can determine the presence of any feasible analyte in the sensor area based on reflected light detected by the light detectors.
  • FIG. 9 is a flowchart showing an example method 900 for performing surface plasmon resonance analysis with a SPR microfluidics device. Some examples may perform the operations described herein with additional operations, fewer operations, operations in a different order, operations in parallel, and some operations differently.
  • the method 900 is described below with respect to the SPR microfluidics system 800 of FIG. 8, however, the method 900 may be performed by any other suitable system or device.
  • the method 900 begins in block 902 as a sensor region of the SPR microfluidics system 800 is cleaned.
  • the sensor region may include a thin metal layer disposed within an air gap of a microfluidic cartridge.
  • a cleaning process may include manipulating, with a mechanical actuator, a droplet of ethanol over the thin metal layer a number of times, effectively cleansing the metal. Subsequently, the sensors are left to air-dry at room temperature for approximately five minutes. Manipulation of the ethanol may be in accordance with any of the methods described with respect to FIG. 1.
  • the metal layer is activated.
  • the metal layer may be activated to immobilize ligands that are placed in contact with the metal layer.
  • a self-assembled monolayer may be formed on the metal layer by manipulating an acid (including but not limited to a mercaptoundecanoic acid) to the metal layer and allowed to interact with the metal layer for a number of hours.
  • carboxyl groups on the metal layers may be activated with ethylene dichloride and N-Hydroxysuccinimide.
  • a ligand is moved to the sensor region.
  • a ligand may be introduced into the air gap and manipulated to the sensor region.
  • the ligands may then be immobilized with respect to the metal layers. The immobilization may be due to the preparation performed in block 904.
  • a sample is moved to the sensor region.
  • the sample may include an analyte.
  • the ligands, immobilized to the metal layer, can bond with particular analytes included in the sample.
  • the sample may be moved to the sensor region by a mechanical actuator providing a compression force to one layer of a microfluidic cartridge.
  • the sensor region may be heated or cooled. This step may be optional, as shown by the dashed lines in FIG. 9. In some cases additional heat or cooling may be desired in the sensor region.
  • a heating, cooling, or heating/cooling element may be disposed within the sensor region. Through this element, additional heat and/or cooling may be provided to liquids in the sensor region.
  • the liquids may include any samples and/or analytes in the sensor region.
  • the presence of an analyte may be determined using surface plasmon resonance.
  • a light source may provide light at a predetermined angle with respect to the metal layer (thin metal layer). Light reflected from the metal layer can be detected with a light detected. The presence of analytes in the sample may be determined based on the detected light.
  • multiple instances of the method of FIG. 9 may be performed serially or in parallel. For example, if a microfluidic cartridge similar to one described in FIG. 7 is used, then the presence of different analytes may be detected through the method 900 performed at different sensor regions.
  • FIG. 10 shows a block diagram of a SPR microfluidics device 1000 that may be one example of any of the microfluidics devices described herein.
  • the SPR microfluidics device 1000 may include a pressure actuator 1020, a light source 1021, a light detector 1022, a heater 1023, a processor 1030, and a memory 1040.
  • the pressure actuator 1020 which is coupled to the processor 1030, may be used to provide forces, including compression and actuation forces to one or more sheets of a microfluidic cartridge.
  • the pressure actuator 1020 may use mechanical, pneumatic, and/or electrical actuators to provide the compression and/or actuation forces.
  • the compression and/or actuation forces may be provided through a controllable stylus.
  • the pressure actuator 1020 may provide positive and/or negative pressure to a lumen of a stylus. In this manner a droplet may be aspirated from a gap of a microfluidic device and drawn into the stylus.
  • the light source 1021 which is coupled to the processor 1030, may provide light at a predetermined angle to any sensor area (any feasible metal layer or sheet).
  • the SPR microfluidics device 1000 may receive a microfluid cartridge, such as the microfluidics cartridge 700 of FIG. 7.
  • the light source 1021 may provide light to one or more sensor areas of the microfluidics cartridge 700.
  • the light source 1021 may be any feasible light source including, but not limited to, monochromatic, white, and laser (coherent) light.
  • the light detector 1022 which is also coupled to the processor 1030, may detect reflected light from any feasible sensor area.
  • the reflected light may change based on any analytes that are bound to the sensor area.
  • the reflected light can indicate the presence or absence of an analyte.
  • various ligands may be immobilized to a reflective metal within the sensor area. The ligands may form bonds with different analytes, that in turn can change the reflective property of the metal.
  • the heater 1023 which is also coupled to the processor 1030 may provide heat to various areas, including areas within or around a microfluidics cartridge.
  • the heater can include a cooler (cooling unit or pad) to reduce ambient temperature. Localized heating or cooling may be advantageous in certain instances, experiments, and/or processes.
  • the processor 1030 which is also coupled to the memory 1040, may be any one or more suitable processors capable of executing scripts or instructions of one or more software programs stored in the SPR microfluidics device 1000 (such as within memory 1040).
  • the memory 1040 may also include a non-transitory computer-readable storage medium (e.g., one or more nonvolatile memory elements, such as EPROM, EEPROM, Flash memory, a hard drive, etc.) that may store the following software modules: a pressure actuator control module 1042 to control the pressure actuator 1020, a heater control module 1044 to process control operations of the heater 1023.
  • each software module includes program instructions that, when executed by the processor 1030, may cause the SPR microfluidics device 1000 to perform the corresponding function(s).
  • the non-transitory computer-readable storage medium of memory 1040 may include instructions for performing all or a portion of the operations described herein.
  • the processor 1030 may execute the pressure actuator control module 1042 to manipulate one or more microfluidic droplets disposed between at least two hydrophobic and oleophobic sheets by applying forces through the pressure actuator 1020.
  • execution of the pressure actuator control module 1042 may cause compressive, pinning, and/or actuation forces to be applied to at least one of the hydrophobic and oleophobic sheets.
  • the forces may be selectively applied to move, separate, combine, and/or mix one or more microfluidic droplets.
  • execution of the pressure actuator control module 1042 may cause a stylus to move across at least one of the hydrophobic and oleophobic sheets, apply a compression force, and cause a droplet to move.
  • the processor 1030 may execute the heater control module 1044 to control temperatures, including localized temperatures in and around sensor areas of the SPR microfluidic device 1000.
  • execution of the heater control module 1044 can cause the heater 1023 to heat or cool (provide less heat) a region.
  • execution of the heater control module 1044 may cause the cooling element to actively cool a region.
  • Execution of the light source control module 1046 may control operations of the light source 1021. In some examples, execution of the light source control module 1046 may cause the light source 1021 to provide light to a sensor area. If the SPR microfluidics device 1000 includes two or more lights, then execution of the light source control module 1046 may enable the processor to control the two or more lights.
  • Execution of the light detector control module 1048 can enable the processor 1030 to receive and analyze data from the light detector 1022. In some examples, execution of the light detector control module 1048 enables the processor 1030 to perform surface plasmon resonance analysis regarding the presence of analytes in an sensor area. [0100] It should be appreciated that all combinations of the foregoing concepts and additional concepts discussed in greater detail below (provided such concepts are not mutually inconsistent) are contemplated as being part of the inventive subject matter disclosed herein and may be used to achieve the benefits described herein.
  • any of the methods (including user interfaces) described herein may be implemented as software, hardware or firmware, and may be described as a non-transitory computer-readable storage medium storing a set of instructions capable of being executed by a processor (e.g., computer, tablet, smartphone, etc.), that when executed by the processor causes the processor to control perform any of the steps, including but not limited to: displaying, communicating with the user, analyzing, modifying parameters (including timing, frequency, intensity, etc.), determining, alerting, or the like.
  • any of the methods described herein may be performed, at least in part, by an apparatus including one or more processors having a memory storing a non-transitory computer-readable storage medium storing a set of instructions for the processes(s) of the method.
  • the computing devices and systems described and/or illustrated herein broadly represent any type or form of computing device or system capable of executing computer-readable instructions, such as those contained within the modules described herein. In their most basic configuration, these computing device(s) may each comprise at least one memory device and at least one physical processor.
  • the term “memory” or “memory device,” as used herein, generally represents any type or form of volatile or non-volatile storage device or medium capable of storing data and/or computer-readable instructions. In one example, a memory device may store, load, and/or maintain one or more of the modules described herein.
  • RAM Random Access Memory
  • ROM Read Only Memory
  • HDD Hard Disk Drives
  • SSDs Solid-State Drives
  • optical disk drives caches, variations or combinations of one or more of the same, or any other suitable storage memory.
  • processor or “physical processor,” as used herein, generally refers to any type or form of hardware-implemented processing unit capable of interpreting and/or executing computer-readable instructions.
  • a physical processor may access and/or modify one or more modules stored in the above-described memory device.
  • Examples of physical processors comprise, without limitation, microprocessors, microcontrollers, Central Processing Units (CPUs), Field-Programmable Gate Arrays (FPGAs) that implement softcore processors, Application-Specific Integrated Circuits (ASICs), portions of one or more of the same, variations or combinations of one or more of the same, or any other suitable physical processor.
  • the method steps described and/or illustrated herein may represent portions of a single application.
  • one or more of these steps may represent or correspond to one or more software applications or programs that, when executed by a computing device, may cause the computing device to perform one or more tasks, such as the method step.
  • one or more of the devices described herein may transform data, physical devices, and/or representations of physical devices from one form to another. Additionally or alternatively, one or more of the modules recited herein may transform a processor, volatile memory, non-volatile memory, and/or any other portion of a physical computing device from one form of computing device to another form of computing device by executing on the computing device, storing data on the computing device, and/or otherwise interacting with the computing device.
  • computer-readable medium generally refers to any form of device, carrier, or medium capable of storing or carrying computer-readable instructions.
  • Examples of computer-readable media comprise, without limitation, transmission-type media, such as carrier waves, and non-transitory-type media, such as magnetic- storage media (e.g., hard disk drives, tape drives, and floppy disks), optical-storage media (e.g., Compact Disks (CDs), Digital Video Disks (DVDs), and BLU-RAY disks), electronic-storage media (e.g., solid-state drives and flash media), and other distribution systems.
  • transmission-type media such as carrier waves
  • non-transitory-type media such as magnetic- storage media (e.g., hard disk drives, tape drives, and floppy disks), optical-storage media (e.g., Compact Disks (CDs), Digital Video Disks (DVDs), and BLU-RAY disks), electronic-storage media (e.g., solid-state drives and flash media), and other
  • the processor as described herein can be configured to perform one or more steps of any method disclosed herein. Alternatively or in combination, the processor can be configured to combine one or more steps of one or more methods as disclosed herein.
  • the device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly.
  • the terms “upwardly”, “downwardly”, “vertical”, “horizontal” and the like are used herein for the purpose of explanation only unless specifically indicated otherwise.
  • first and second may be used herein to describe various features/elements (including steps), these features/elements should not be limited by these terms, unless the context indicates otherwise. These terms may be used to distinguish one feature/element from another feature/element. Thus, a first feature/element discussed below could be termed a second feature/element, and similarly, a second feature/element discussed below could be termed a first feature/element without departing from the teachings of the present invention.
  • any of the apparatuses and methods described herein should be understood to be inclusive, but all or a sub-set of the components and/or steps may alternatively be exclusive, and may be expressed as “consisting of’ or alternatively “consisting essentially of” the various components, steps, sub-components or sub-steps. [0119] As used herein in the specification and claims, including as used in the examples and unless otherwise expressly specified, all numbers may be read as if prefaced by the word "about” or “approximately,” even if the term does not expressly appear.
  • a numeric value may have a value that is +/- 0.1% of the stated value (or range of values), +/- 1% of the stated value (or range of values), +/- 2% of the stated value (or range of values), +/- 5% of the stated value (or range of values), +/- 10% of the stated value (or range of values), etc.
  • Any numerical values given herein should also be understood to include about or approximately that value, unless the context indicates otherwise. For example, if the value "10" is disclosed, then “about 10" is also disclosed.
  • any numerical range recited herein is intended to include all sub-ranges subsumed therein. It is also understood that when a value is disclosed that “less than or equal to” the value, “greater than or equal to the value” and possible ranges between values are also disclosed, as appropriately understood by the skilled artisan. For example, if the value "X” is disclosed the “less than or equal to X” as well as “greater than or equal to X” (e.g., where X is a numerical value) is also disclosed. It is also understood that the throughout the application, data is provided in a number of different formats, and that this data, represents endpoints and starting points, and ranges for any combination of the data points.

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Abstract

L'invention concerne un appareil, un système et un procédé pour effectuer une analyse par résonance plasmonique de surface avec une manipulation microfluidique à base mécanique. L'appareil/système peut comprendre deux feuilles séparées par un espace. Des fluides à l'intérieur de l'espace sont manipulés par l'application de forces de compression pour réduire localement l'espace, amenant les fluides à se déplacer. L'appareil/système peut comprendre une région de capteur ayant une feuille métallique mince disposée à proximité de l'espace. Des ligands peuvent être immobilisés par rapport à la feuille métallique et les ligands peuvent attirer des analytes. Les analytes peuvent être détectés sur la base de la lumière réfléchie par la feuille métallique. Des échantillons de test, des ligands et d'autres liquides sont déplacés dans la région de capteur par l'intermédiaire de forces de compression.
PCT/US2024/059240 2023-12-07 2024-12-09 Résonance plasmonique de surface avec manipulation microfluidique mécanique Pending WO2025123049A1 (fr)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6579721B1 (en) * 1999-07-30 2003-06-17 Surromed, Inc. Biosensing using surface plasmon resonance
US20100165784A1 (en) * 2008-12-31 2010-07-01 Microchip Biotechnologies, Inc., A California Corporation Instrument with microfluidic chip
US20170023477A1 (en) * 2006-03-10 2017-01-26 Reuven Duer Waveguide-based detection system with scanning light source
US20230219092A1 (en) * 2022-01-12 2023-07-13 Miroculus Inc. Methods of mechanical microfluidic manipulation
WO2023178432A1 (fr) * 2022-03-23 2023-09-28 Nicoya Lifesciences, Inc. Analyse optique sur des cartouches microfluidiques numériques (dmf)

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6579721B1 (en) * 1999-07-30 2003-06-17 Surromed, Inc. Biosensing using surface plasmon resonance
US20170023477A1 (en) * 2006-03-10 2017-01-26 Reuven Duer Waveguide-based detection system with scanning light source
US20100165784A1 (en) * 2008-12-31 2010-07-01 Microchip Biotechnologies, Inc., A California Corporation Instrument with microfluidic chip
US20230219092A1 (en) * 2022-01-12 2023-07-13 Miroculus Inc. Methods of mechanical microfluidic manipulation
WO2023178432A1 (fr) * 2022-03-23 2023-09-28 Nicoya Lifesciences, Inc. Analyse optique sur des cartouches microfluidiques numériques (dmf)

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