# US 12,758,976 B2 · Ultra high efficiency microfluidic platform

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- Number: US 12,758,976 B2
- Document ID: US12758976B2
- Status: Granted
- Kind: B2
- Application number: 18/820,655
- Filed: 2024-08-30
- Published: 2024-12-19
- Granted: 2026-10-13
- Earliest claimed: 2020-04-23
- Assignees: The Texas A&M University System
- Applicants: The Texas A&M University System
- Inventors: Arum Han; Adrian Guzman; Han Zhang; Jose Wippold; Jing Dai
- Web page: https://patentgrep.com/patent/US12758976B2

## CPC

- B01L 3/502784: {specially adapted for droplet or plug flow, e.g. digital microfluidics}
- B01L 2200/027: for microfluidic devices
- B01L 2200/0647: Handling flowable solids, e.g. microscopic beads, cells, particles
- B01L 2200/12: Specific details about manufacturing devices
- B01L 2200/16: Reagents, handling or storing thereof
- B01L 2400/086: using baffles or other fixed flow obstructions
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE

## Abstract

A combination micro/macro-fluidic analysis system with one or more of a droplet transition unit, a droplet cleaving unit, a droplet synchronization, and a merging unit to enable highly efficient complex droplet microfluidic assays.

## Claims

### Claim 1

A droplet production system, comprising:
a droplet cleaving unit comprising two or more microfluidic channels, wherein a first continuous-phase fluid flows in a first microfluidic channel, a second fluid comprising a first set of multi-phase emulsion droplets flows in a second microfluidic channel, and wherein the first continuous-phase fluid in the first microfluidic channel is cleaved into a second set of droplets through the use of the multi-phase emulsion droplets in the second microfluidic channel;
a droplet auto-synchronization unit configured to places the first set of multi-phase emulsion droplets in close proximity to the second set of droplets generated from cleaving of the continuous-phase flow to form paired droplets, wherein a pairing ratio between the first set and second set of droplets varies depending on the conditions utilized in the droplet production system; and
a merging unit that merges the paired droplets into a single droplet;
and wherein the droplet production system is configured to achieve high-efficiency droplet pairing and merging.

### Claim 2 (depends on 1)

The droplet production system of claim 1, wherein the paired droplets are merged using an electric field, acoustic wave, convective heating, or other droplet merging methods.

### Claim 3 (depends on 2)

The droplet production system of claim 2, wherein one or more meandering channels or merging zones are present and are placed to allow the paired droplets to be merged at more than one location.

### Claim 4 (depends on 1)

The droplet production system of claim 1, wherein flow of the second fluid is adjusted to vary size of the multi-phase emulsion droplets, rate of flow, and spacing between the multi-phase emulsion droplets.

### Claim 5 (depends on 1)

The droplet production system of claim 1, wherein size of the second set of droplets is varied by adjusting one or more of flow of the continuous-phase fluid or the second fluid, dimensions of the first microfluidic channel, or dimensions of the second microfluidic channel.

### Claim 6 (depends on 1)

The droplet production system of claim 1, wherein various pairing ratios are obtained by adjusting flow parameters of the continuous-phase fluid or the second fluid or both.

### Claim 7 (depends on 1)

The droplet production system of claim 1, wherein the one or more of droplet cleaving and the droplet auto-synchronization units are connected in series to create two or more paired droplets for merging.

### Claim 8 (depends on 1)

The droplet production system of claim 1, wherein the continuous-phase fluid, the second fluid, or both contain one or more reagents, microparticles, microbeads, and/or cells.

### Claim 9 (depends on 1)

The droplet production system of claim 1, wherein the two or more microfluidic channels are stacked in any spatial direction with respect to a base plane of the system.

### Claim 10

A fluid sample testing system, comprising:
the droplet cleaving unit comprising two or more microfluidic channels, wherein a fluid sample flows in a first microfluidic channel, a first fluid comprising a first set of multi-phase emulsion droplets flows in a second microfluidic channel, and wherein the fluid sample in the first microfluidic channel is configured to be cleaved into a second set of droplets through the use of the multi-phase emulsion droplets in the second microfluidic channel;
a droplet auto-synchronization unit configured to places the first set of multi-phase emulsion droplets from the first fluid in close proximity to the second set of droplets generated from the fluid sample by cleaving to form paired droplets, wherein a pairing ratio between the first set of droplets and second set of droplets varies depending on the conditions utilized in the fluid sample testing system; and
a merging unit that merges the paired droplets into a single merged droplet-, wherein the fluid sample testing system is configured to achieve high-efficiency droplet pairing and merging.

### Claim 11 (depends on 10)

The fluid sample testing system of claim 10, wherein the paired droplets are merged using an electric field, acoustic wave, convective heating, or other merging methods.

### Claim 12 (depends on 10)

The fluid sample testing system of claim 10, wherein one or more meandering channels or merging zones are present and are placed to allow the paired droplets to be merged at more than one location.

### Claim 13 (depends on 10)

The fluid sample testing system of claim 10, wherein flow of the first fluid is adjusted to vary size of the multi-phase emulsion droplets, rate of flow, and spacing between the multi-phase emulsion droplets.

### Claim 14 (depends on 10)

The fluid sample testing system of claim 10, wherein size of the second set of droplets is varied by adjusting one or more of flow of the fluid sample or the first fluid, dimensions of the first microfluidic channel, or dimensions of the second microfluidic channel.

### Claim 15 (depends on 10)

The fluid sample testing system of claim 10, wherein various droplet pairing ratios are obtained by adjusting flow parameters of the fluid sample or the first fluid or both.

### Claim 16 (depends on 10)

The fluid sample testing system of claim 10, wherein the fluid sample, the first fluid, or both contains one or more reagents, microparticles, microbeads, cells, or combinations thereof.

### Claim 17 (depends on 10)

The fluid sample testing system of claim 10, wherein the merged droplet contains two or more reagents, hydrogels, beads, particles, cells, or combinations thereof.

### Claim 18 (depends on 10)

The fluid sample testing system of claim 10, wherein the two or more microfluidic channels are stacked in any spatial direction with respect to a base plane of the system.
