# US 12,109,565 B2 · Microfluidic device and a method for provision of emulsion droplets

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- Number: US 12,109,565 B2
- Document ID: US12109565B2
- Status: Granted
- Kind: B2
- Application number: 17/426,554
- Filed: 2020-01-31
- Published: 2022-04-07
- Granted: 2024-10-08
- Earliest claimed: 2019-01-31
- Assignees: Samplix Aps
- Applicants: Samplix Aps
- Inventors: Thomas Kvist; Soléne Cherre; Marie Just Mikkelsen
- Web page: https://patentgrep.com/patent/US12109565B2

## CPC

- B01F 23/41: Emulsifying
- B01L 3/502769: {characterised by multiphase flow arrangements}
- B01F 23/4144: {Multiple emulsions, in particular double emulsions, e.g. water in oil in water; Three-phase emulsions}
- B01F 33/3011: using a sheathing stream of a fluid surrounding a central stream of a different fluid, e.g. for reducing the cross-section of the central stream or to produce droplets from the central stream
- B01F 33/813: {mixing simultaneously in two or more mixing receptacles}
- B01L 2200/0673: Handling of plugs of fluid surrounded by immiscible fluid
- B01L 2300/0883: Serpentine channels
- B01F: MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING (mixing paints B44D3/06)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE

## Abstract

A microfluidic device (100) comprises an emulsification section (101) comprising one or more emulsification units (170); and a container section (102) comprising one or more groups of containers comprising one group of containers for each emulsification unit; each emulsification unit (170) comprising a fluid conduit network (135) comprising: a plurality of supply conduits comprising a primary supply conduit (103) and a secondary supply conduit (106); a transfer conduit (112); and a first fluid junction (120) providing fluid communication between the primary supply conduit (103), the secondary supply conduit (106), and the transfer conduit (112); each group of containers (103) comprising a plurality of containers comprising an intermediate chamber (174), a collection container (134), and one or more supply containers (131) comprising a secondary supply container, the secondary supply container (131) defining a secondary supply cavity, the secondary supply container (131) comprising a secondary orifice (177) extending from the secondary supply cavity and a primary orifice (176) extending from the secondary supply cavity, the collection container (134) being in fluid communication with the transfer conduit (112) of the corresponding emulsification unit (170) via a collection orifice of the collection container (134), the secondary supply container (131) being in fluid communication with the secondary supply conduit (106) of the corresponding emulsification unit (170) via the secondary orifice (177), the secondary supply container (131) being in fluid communication with the intermediate chamber (174) of the same group of containers (103) via the primary orifice (176), the intermediate chamber (174) being in fluid communication with the first fluid junction (120) of the corresponding emulsification unit (170) via the primary supply conduit (103) of the corresponding emulsification unit (170). Furthermore a method of manufacturing said device and a method for providing emulsion droplets using such a microfluidic device.

## Claims

### Claim 1

A microfluidic device comprising:
an emulsification section comprising one or more emulsification units; and a container section comprising one or more groups of containers comprising
one group of containers for each emulsification unit;
each emulsification unit comprising a fluid conduit network comprising: a plurality of supply conduits comprising a primary supply conduit and a secondary supply conduit;
a transfer conduit; and
a first fluid junction providing fluid communication between the primary supply conduit, the secondary supply conduit, and the transfer conduit; each group of containers comprising a plurality of containers comprising an intermediate chamber, a collection container, and one or more supply containers comprising a secondary supply container,
the secondary supply container defining a secondary supply cavity,
the secondary supply container comprising a secondary orifice extending from the secondary supply cavity and a primary orifice extending from the secondary supply cavity,
the collection container being in fluid communication with the transfer conduit of the corresponding emulsification unit via a collection orifice of the collection container,
the secondary supply container being in fluid communication with the secondary supply conduit of the corresponding emulsification unit via the secondary orifice,
the secondary supply container being in fluid communication with the intermediate chamber of the same group of containers via the primary orifice, the intermediate chamber being in fluid communication with the first fluid junction of the corresponding emulsification unit via the primary supply conduit of the corresponding emulsification unit.

### Claim 2 (depends on 1)

The microfluidic device according to claim 1, wherein the primary orifice is configured for accommodating a distal end zone of a pipette tip and is configured for forming a seal with the pipette tip when the distal end zone is accommodated by and pressed against the primary orifice.

### Claim 3 (depends on 2)

The microfluidic device according to claim 2, wherein a surface tangent of the primary orifice is conical and tapering in a direction away from the secondary supply cavity.

### Claim 4 (depends on 3)

The microfluidic device according to claim 3, wherein the primary orifice extends from a first primary perimeter bordering the secondary supply cavity to at least a second primary perimeter, wherein the first primary perimeter is configured to enable the distal end of the pipette tip to pass
through, and wherein the second primary perimeter is circular and configured
to hold and form a seal with the distal end zone of the pipette tip when the distal end zone of the pipette tip is pressed against the second primary perimeter, and wherein the smallest diameter of the first primary perimeter is larger than the diameter of the second primary perimeter.

### Claim 5 (depends on 4)

The microfluidic device according to claim 4, wherein the smallest diameter of the first primary perimeter is between 9 mm and 0.5 mm, and wherein the diameter of the second primary perimeter is between 0.10 mm and 3.0 mm.

### Claim 6 (depends on 1)

The microfluidic device according to claim 1, wherein the intermediate chamber has an extension of at least 8 mm, a width of 100 μm to 9 mm, a depth of 50 μm to 5 mm, wherein the width to depth ratio is 0.3 to 5, and wherein the width multiplied by the length is at least 100 mm2.

### Claim 7 (depends on 1)

The microfluidic device according to claim 1, wherein the intermediate chamber extends along a curved line comprising at least two parts extending in opposite directions.

### Claim 8 (depends on 1)

The microfluidic device according to claim 1, wherein
the intermediate chamber has a serpentine-shaped part.

### Claim 9 (depends on 1)

The microfluidic device according to claim 1, wherein the collection container has a bottom part having an inclining surface, and
wherein the collection orifice is provided at the lowermost part of the collection container.

### Claim 10 (depends on 1)

The microfluidic device according to claim 1,
comprising a plurality of components forming the emulsification section and the container section, wherein each component of the plurality of components comprises at least one side facing and being attached to a side of another component of the plurality of components, such that each component is fixedly attached to at least one other component, and such that the plurality
of components forms a fixedly connected unit, and wherein the plurality of components comprises a first component and a second component being fixed to and facing each other, wherein the fluid conduit network of each emulsification section is formed in part by the first component and in part by the second component, and wherein the intermediate chamber of each group
of containers is formed in part by a first recess in one component of the
plurality of components, such as one of the first component and the second component, and in part by a first flat surface of another component of the plurality of components, such as another one of the first component and the second component.

### Claim 11 (depends on 10)

The microfluidic device according to claim 10, wherein the secondary supply container of each group of containers, the collection container of each group of containers, and the first recess of the intermediate chamber of each group of containers are provided in the same component of the plurality of
components, and wherein the secondary supply container and the collection container comprises respective top openings facing in the opposite direction than the first recess of the intermediate chamber.

### Claim 12 (depends on 11)

The microfluidic device according to claim 11, wherein the component comprising the first recess of the intermediate chamber comprises a plate-like section where the first recess is provided, wherein the thickness of the plate-like section immediately next to the recess is between 0.5 mm and 3 mm.

### Claim 13 (depends on 10)

The microfluidic device according to any of the claim 10, wherein the plurality of components comprises a third component, wherein the secondary supply container of each group of containers and the collection container of each group of containers are provided in the third component.

### Claim 14 (depends on 1)

An assembly comprising the microfluidic device according to claim 1, a thermal structure, and a holder configured to provide a thermal connection between the thermal structure and a bottom part of the microfluidic device, wherein most of the intermediate chamber of each group of containers is provided within 5 mm from the thermal structure.

### Claim 15 (depends on 1, 14)

A kit comprising:
one or more of the microfluidic device according to claim 1 and/or one or more of the assembly according to claim 14; and
a plurality of fluids configured for use with the microfluidic device;
the plurality of fluids comprising a sample buffer and an oil, the kit comprising an enzyme and nucleotides,
wherein the sample buffer has a lower density than the oil.

### Claim 16 (depends on 1)

A method for providing emulsion droplets, the method comprising use of:
the microfluidic device according to claim 1
the method comprising the following steps:
accommodating a distal end zone of a pipette tip into the primary orifice and injecting a first fluid from the pipette tip into the intermediate chamber of a first group of containers;
providing a second fluid to the secondary supply container of the first group of containers; and
providing a pressure difference between the secondary supply container of the first group of containers and the collection container of the first group of containers, such that the pressure within the
secondary supply container of the first group of containers is higher than within the collection container of the first group of containers.

### Claim 17 (depends on 10)

A method of providing a microfluidic device according to claim 10, the method comprising:
providing the plurality of components; and
assembling the plurality of components such that each component is fixedly
attached to at least one other component, and such that the plurality of components forms a fixedly connected unit, and such that each fluid conduit network is formed in part by the second component and in part by the first component, and wherein the first component faces the second component.