# US 11,998,912 B2 · Tubing-free, sample-to-droplet microfluidic system and chip

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- Number: US 11,998,912 B2
- Document ID: US11998912B2
- Status: Granted
- Kind: B2
- Application number: 17/954,000
- Filed: 2022-09-27
- Published: 2023-04-13
- Granted: 2024-06-04
- Earliest claimed: 2021-09-27
- Assignees: The Johns Hopkins University
- Applicants: The Johns Hopkins University
- Inventors: Tza-Huei Jeff Wang; Kuangwen Hsieh; Yi-Fan Frank Hsieh; Aniruddha Mrithinjay Kaushik; Fangchi Shao; Pengfei Zhang
- Web page: https://patentgrep.com/patent/US11998912B2

## CPC

- B01L 3/502738: {characterised by integrated valves (throttle valves in microfluidic sample containers B01L3/502746)}
- B01L 3/502784: {specially adapted for droplet or plug flow, e.g. digital microfluidics}
- B25J 9/1697: {Vision controlled systems}
- B01L 2300/0636: Integrated biosensor, microarrays
- B01L 2300/0816: Cards, e.g. flat sample carriers usually with flow in two horizontal directions
- B01L 2300/0883: Serpentine channels
- B01L 2400/02: Drop detachment mechanisms of single droplets from nozzles or pins
- B01L 2400/049: vacuum
- B01L 2400/0605: check valves
- B01L 2400/0655: pinch valves
- B01L 2400/0666: Solenoid valves
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B25J: MANIPULATORS; CHAMBERS PROVIDED WITH MANIPULATION DEVICES ({manipulators specially adapted for use in surgery A61B34/70; manipulators used in cleaning hollow articles B08B9/04}; manipulators associated with rolling mills B21B39/20; manipulators associated with forging machines B21J13/10; {manipulators associated with picking-up and placing mechanisms B23P19/007}; means for holding wheels or parts thereof B60B30/00; {vehicles with ground-engaging propulsion means, e.g. walking members B62D57/02, B62D57/032; devices for picking-up and depositing articles or materials between conveyors B65G47/90, B65G47/91; manipulators with gripping or holding means for transferring packages B65H67/065}; cranes B66C; {manipulators used in the protection or supervision of pipe-line installations F17D5/00; walking equipment adapted for nuclear steam-generators F22B37/006}; manipulators specially adapted for, or associated with, nuclear reactors G21C; {apparatus used for handling wafers during manufacture or treatment of semiconductor H10P72/50})

## Abstract

A tubing-free, sample-to-droplet microfluidic system includes a tubing-free, sample-to-droplet microfluidic chip; a valve control system connected to the tubing-free, sample-to-droplet microfluidic chip; a vacuum system fluidly connected to the tubing-free, sample-to-droplet microfluidic chip; and a droplet formation pressure system fluidly connected to the tubing-free, sample-to-droplet microfluidic chip. A microfluidic chip for a tubing-free, sample-to-droplet microfluidic system includes a tubing-free, sample-to-droplet interface section; a droplet mixing section in fluid connection with the tubing-free, sample-to-droplet interface section to received droplets therefrom; an incubation section in fluid connection with the droplet mixing section to receive droplets therefrom; and a detection section in fluid connection with the incubation section to receive droplets therefrom.

## Claims

### Claim 1

A sample-to-droplet microfluidic system, comprising:
a sample-to-droplet microfluidic chip;
a valve control system connected to said sample-to-droplet microfluidic chip;
a vacuum system fluidly connected to said sample-to-droplet microfluidic chip; and
a droplet formation pressure system fluidly connected to said sample-to-droplet microfluidic chip,
wherein said sample-to-droplet microfluidic chip comprises:
a sample-to-droplet interface section;
a droplet mixing section in fluid connection with said sample-to-droplet interface section to received droplets therefrom;
an incubation section in fluid connection with said droplet mixing section to receive droplets therefrom; and
a detection section in fluid connection with said incubation section to receive droplets therefrom;
wherein said sample-to-droplet interface section comprises:
a first sample input channel with a first open port configured to receive a sample input,
a vacuum channel fluidly connected to said first sample input channel when a pair of intermediate valves therein are open, a first droplet forming region being between said pair of intermediate valves,
a first fluid pressure channel arranged to intercept said first droplet forming region with a valve prior to said first droplet forming region, said first fluid pressure channel further intercepting a droplet channel with a valve therebetween, said droplet channel leading to said droplet mixing section,
wherein said sample-to-droplet interface section further comprises:
a second sample input channel with an open port configured to receive a sample input, said vacuum channel being further fluidly connected to said second sample input channel when a pair of intermediate valves therein are open, a second droplet forming region being between said pair of intermediate valves, and
a second fluid pressure channel arranged to intercept said second droplet forming region with a valve prior to said droplet forming region, said second fluid pressure channel further intercepting said droplet channel with a valve therebetween.

### Claim 2 (depends on 1)

The microfluidic system according to claim 1, further comprising a robotic system configured to acquire a selected amount of a sample and to deliver said selected amount of said sample to said open port of said first sample channel.

### Claim 3 (depends on 2)

The microfluidic system according to claim 2, wherein said robotic system is further configured to deliver said selected amount of said sample to said open port of said second sample channel.

### Claim 4 (depends on 1)

The microfluidic system according to claim 1, wherein said microfluidic chip comprises a fluid flow layer and a control layer constructed such that said first sample input channel, said vacuum channel, and said first fluid pressure channel are defined within said fluid flow layer.

### Claim 5 (depends on 4)

The microfluidic chip according to claim 4, wherein said second sample input channel, and said second fluid pressure channel are defined within said fluid flow layer.

### Claim 6 (depends on 4)

The microfluidic chip according to claim 4, wherein valve control channels are defined within said control layer, said valve control channels being suitable for carrying fluid for pneumatic control of said valves.

### Claim 7

A microfluidic chip for a sample-to-droplet microfluidic system, comprising:
a sample-to-droplet interface section;
a droplet mixing section in fluid connection with said sample-to-droplet interface section to received droplets therefrom;
an incubation section in fluid connection with said droplet mixing section to receive droplets therefrom; and
a detection section in fluid connection with said incubation section to receive droplets therefrom;
wherein said sample-to-droplet interface section comprises:
a first sample input channel with an open port configured to receive a sample input,
a vacuum channel fluidly connected to said first sample input channel when a pair of intermediate valves therein are open, a first droplet forming region being between said pair of intermediate valves,
a first fluid pressure channel arranged to intercept said first droplet forming region with a valve prior to said droplet forming region, said first fluid pressure channel further intercepting a droplet channel with a valve therebetween, said droplet channel leading to said droplet mixing section, and
wherein said sample-to-droplet interface section further comprises:
a second sample input channel with an open port configured to receive a sample input, said vacuum channel being further fluidly connected to said second sample input channel when a pair of intermediate valves therein are open, a second droplet forming region being between said pair of intermediate valves, and
a second fluid pressure channel arranged to intercept said second droplet forming region with a valve prior to said droplet forming region, said second fluid pressure channel further intercepting said droplet channel with a valve therebetween.

### Claim 8 (depends on 7)

The microfluidic chip according to claim 7, wherein said microfluidic chip comprises a fluid flow layer and a control layer constructed such that said first sample input channel, said vacuum channel, and said first fluid pressure channel are defined within said fluid flow layer.

### Claim 9 (depends on 8)

The microfluidic chip according to claim 8, wherein said second sample input channel, and said second fluid pressure channel are defined within said fluid flow layer.

### Claim 10 (depends on 9)

The microfluidic chip according to claim 9, wherein valve control channels are defined within said control layer, said valve control channels being suitable for carrying fluid for pneumatic control of said valves.
