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EP-4739436-A1 - MICROFLUIDIC TWO-DIMENSIONAL CAPILLARY MANIPULATION DEVICES AND METHODS

EP4739436A1EP 4739436 A1EP4739436 A1EP 4739436A1EP-4739436-A1

Abstract

Methods and apparatuses 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 first and second sheets may be hydrophobic and oleophobic or may include hydrophobic and oleophobic coating.

Inventors

  • JEBRAIL, MAIS J.
  • CHRISTODOULOU, Foteini
  • LAL, Rohit
  • CERVANTES, Eduardo
  • CARVAJAL, Ana, Eugenia

Assignees

  • Integra Biosciences AG

Dates

Publication Date
20260513
Application Date
20240708

Claims (20)

  1. 1. A mechanical microfluidics actuator apparatus configure to couple to a liquid handling robot, the apparatus comprising: a seating region configured to couple to a cartridge; a stylus configured to deform an upper surface of the cartridge when the cartridge is seated in the seating region; an applicator driver subassembly coupled to the stylus and configured to control the movement of the stylus laterally along the upper surface of the cartridge while vertically deforming the upper surface of the cartridge; and a coupling configured to couple the microfluidics actuator apparatus to the liquid handling robot.
  2. 2. The apparatus of claim 1, further comprising a controller configured to control operation of the applicator drive assembly and the liquid handling robot.
  3. 3. The apparatus of claim 1, further comprising the liquid handling robot.
  4. 4. The apparatus of claim 1, wherein the seating regions comprises one or more suction ports configured to secure the cartridge thereto.
  5. 5. The apparatus of claim 1, wherein the applicator driver subassembly comprises one or more drivers.
  6. 6. The apparatus of claim 5, wherein the one or more drivers comprises an x and/or y motion driver, and/or a z-motion driver.
  7. 7. The apparatus of claim 1, wherein the applicator driver subassembly comprises a frame or gantry onto which the stylus may be driven to change position and/or to apply force to the cartridge.
  8. 8. The apparatus of claim 1, wherein the applicator driver subassembly is configured to move the stylus to apply a pinning compression force to divide a first fluidic droplet in the cartridge and to apply an actuation compression force proximate to the pinning compression force to elongate and form a second fluidic droplet from the first fluidic droplet and wherein the pinning compression force is greater than the actuation compression force.
  9. 9. The apparatus of claim 1, wherein the applicator driver subassembly is configured to move the stylus to apply a compression force to the cartridge between two or more separate fluidic droplets, and to release the compression force to combine the two or more separate fluidic droplets into a single fluidic droplet.
  10. 10. The apparatus of claim 1, wherein the applicator driver subassembly is configured to move the stylus alternately to apply a first compression force and a second compression force different than the first compression force to the cartridge to mix together two or more separate fluidic droplets.
  11. 11. The apparatus of claim 1, wherein the applicator driver subassembly is configured to move the stylus to mix together two or more fluidic droplets by repeatedly applying and releasing a compression force to the cartridge adjacent to the two or more fluidic droplets.
  12. 12. The apparatus of claim 1, wherein the applicator driver subassembly is configured to control a magnet to attract ferrous particles suspended within a fluidic droplet in the cartridge.
  13. 13. The apparatus of claim 1, wherein the applicator driver subassembly is configured to re-suspend one or more ferrous particles in a fluidic droplet in the cartridge by applying and releasing a compression force to the fluidic droplet and disabling a magnet.
  14. 14. The apparatus of claim 1, wherein the seating region comprises one or more projections configured to deform a film on the cartridge to form one or more channels.
  15. 15. The apparatus of claim 1, further comprising a thermal control region in the seating region.
  16. 16. A mechanical microfluidics actuator apparatus, the apparatus comprising: a seating region configured to couple to a cartridge; a stylus configured to apply mechanical pressure to deform an upper surface of the cartridge when the cartridge is seated in the seating region; an applicator driver subassembly coupled to the stylus and configured to control the movement of the stylus laterally along the upper surface of the cartridge while vertically deforming the upper surface of the cartridge; one or more well-forming surfaces extending proud of an upper seating surface of the seating region; and one or more suction ports configured to pull a lower surface of the cartridge against the upper searing surface so that the lower surface of the cartridge confirms with the well-forming surface.
  17. 17. The apparatus of claim 16, wherein the well-forming surface is configured to form a heating/cooling well in thermal contract with a thermally controlled region of the seating region.
  18. 18. The apparatus of claim 16, further comprising a controller configured to control operation of the applicator drive assembly and the thermally controlled region.
  19. 19. The apparatus of claim 16, further comprising the liquid handling robot.
  20. 20. The apparatus of claim 16, wherein the applicator driver subassembly comprises one or more drivers.

Description

MICROFLUIDIC TWO-DIMENSIONAL CAPILLARY MANIPULATION DEVICES AND METHODS CLAIM OF PRIORITY [0001] This patent application claims priority to U.S. provisional patent application no. 63/512,576, filed on July 7, 2023, and titled “MICROFLUIDIC TWO-DIMENSIONAL CAPILLARY MANIPULATION DEVICES AND METHODS,” herein incorporated by reference in its entirety. INCORPORATION BY REFERENCE [0002] All publications and patent applications mentioned in this specification are herein incorporated by reference in their entirety to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. BACKGROUND [0003] 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. Microfluidic devices may include micro-channels and require microminiaturized devices containing chambers and tunnels through which fluids flow or are confined. [0004] For example, digital microfluidics (DMF) is a powerful technique for simple and precise manipulation of microscale droplets of fluid. DMF has rapidly become popular for chemical, biological, and medical applications, as it allows straightforward control over multiple reagents (no pumps, valves, or tubing required), facile handling of both solids and liquids (no channels to clog), and compatibility with even troublesome reagents (e.g., organic solvents, corrosive chemicals) because hydrophobic surfaces (typically Teflon-coated) in contact with the droplets of fluid are chemically inert. However, 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. SUMMARY OF THE DISCLOSURE [0005] Described herein are methods and apparatuses for mechanically actuating (e.g., moving, mixing, etc.) on or more droplets within an air gap. These methods may include one or more wells, and one or more regions for cell culture (e.g., one or more hydrophilic regions), and method of using any of these cartridges in one or more medical or medically- related procedures. For example, the methods described herein may include amplifying polynucleotides, performing assays, culturing cells (and performing assays on the cultured cells), etc. [0006] The first sheet and the second sheet may each include hydrophobic and oleophobic surfaces facing the air gap. Either or both surfaces may be functionalized, e.g., to include hybridization regions, such as primer hybridization region). In general, these methods may include the use of a mechanical force actuator that can be driven to locally deform the first, elastically deformable sheet to form localized region of lower gap height (e.g., thickness) adjacent to a droplet and can be moved along the surface of the first sheet to pull the droplet after it to translate the region of locally reduced gap height. The droplet will follow the region of lower gap height within the air gap by capillary action. [0007] In general, these methods and apparatuses may be used for preparing, manipulating and/or analyzing fluidic droplets, such as microfluidic droplets. For example, described herein are microfluidic apparatuses that may be especially helpful for handling and analyzing a clinical, laboratory, biological, or chemical samples. These apparatuses may generally operate by applying a mechanical force, such as a compression force, to an elastically deformable sheet that at least partially covers an air gap over a subregion of the air gap, to reduce the height of the air gap in a region that is adjacent to a droplet, causing the droplet to move towards this region of reduced height. By controlling the relative height of the air gap near the droplet (e.g., by controlling the application of force to deform the elastically deformable sheet), a droplet may be efficiently and quickly moved around the air gap, allowing processing of the droplet including combining the droplet, dividing the droplet, mixing the droplet, cooling/heating the droplet (e.g., thermocycling the droplet), using magnetic particles within the droplet (e.g., to bind/remove materials from the droplet) and the like. [0008] Described herein are apparatuses (systems, devices, etc.) for controlling microfluidic movement, e.g., droplet movement) on a surface by mechanical means. These apparatuses may be referred to herein as mechanical microfluidics actuation devices (“mechanical microfluidics actuators”) and may include a force applicator for applying force to an elastically deformable sheet that at least partially encloses an air gap within which one or more droplets resides. The elastically deformable she