Systems, articles, and methods for flowing particles

Patent metadata

Field	Value
Publication number	US-11162886-B2
Application number	US-201815940001-A
Country	US
Kind code	B2
Filing date	Mar 29, 2018
Priority date	Mar 31, 2017
Publication date	Nov 2, 2021
Grant date	Nov 2, 2021

Abstract

Systems and methods for flowing particles, such as biological entities, in a fluidic channel(s) are generally provided. In some cases, the systems described herein are designed such that a single particle may be isolated from a plurality of particles and flowed into a fluidic channel (e.g., a microfluidic channel) and/or collected e.g., on fluidically isolated surfaces. For example, the single particle may be present in a plurality of particles of relatively high density and the single particle is flowed into a fluidic channel, such that it is separated from the plurality of particles. The particles may be spaced within a fluidic channel so that individual particles may be measured/observed over time. In certain embodiments, the particle may be a biological entity. Such article and methods may be useful, for example, for isolating single cells into individual wells of multi-well cell culture dishes (e.g., for single-cell analysis).

First claim

What is claimed:

1. A method, comprising:
flowing a fluid comprising a first group of a plurality of particles in a first fluidic channel, the first fluidic channel in fluidic communication with a second fluidic channel, wherein a difference in pressure between the first fluidic channel and the second fluidic channel results in a single particle from the first group entering the second fluidic channel;
detecting, with a detector, the presence of the single particle in the second fluidic channel;
changing a flow rate of the fluid in the first fluidic channel such that at least a portion of remaining particles of said first group of the plurality of particles flow through the first fluidic channel, and
flowing the single particle through the second fluidic channel such that no additional particles from the first group of the plurality of particles enter into the second fluidic channel, wherein the single particle is maintained at a constant flow rate in the second fluidic channel while flowing additional particles through the first fluidic channel.

2. The method as in claim 1 , wherein the plurality of particles are a plurality of biological entities.

3. The method as in claim 2 , wherein the plurality of biological entities comprise virions, bacteria, protein complexes, exosomes, cells, or fungi.

4. The method as in claim 1 , wherein the first fluidic channel has an average cross-sectional dimension of greater than or equal to 5 microns and less than or equal to 2 mm.

5. The method as in claim 1 , wherein the second fluidic channel has an average cross-sectional dimension of greater than or equal to 50 microns and less than or equal to 2 mm.

6. The method as in claim 1 , wherein the average cross-sectional dimension of the first fluidic channel to the average cross-sectional dimension of the second fluidic channel is at least 1 and less than or equal to 10.

7. The method as in claim 1 , wherein a density of particles in the first fluidic channel is greater than or equal to 100 particles per milliliter and less than or equal to 1,000,000 particles per milliliter.

8. The method as in claim 1 , wherein a fluidic pressure at the intersection during the step of changing the flow rate is within less than or equal to 10% and greater than or equal to 0.01% of the fluidic pressure at the intersection during the step of flowing the fluid comprising the first group of the plurality of particles in the first fluidic channel.

9. The method as in claim 1 , wherein a flow rate of the fluid in the second fluidic channel during the step of changing the flow rate is within less than or equal to 10% and greater than or equal to 0.01% of the flow rate of the fluid in the second fluidic channel during the step of flowing the fluid comprising the first group of the plurality of particles in the first fluidic channel.

10. The method as in claim 1 , comprising flowing the fluid comprising the first group of the plurality of particles and a second group of the plurality of particles in the first fluidic channel, wherein a difference in pressure between the first fluidic channel and the second fluidic channel results in at least a second particle from the second group entering the second fluidic channel, the particles within the second fluidic channel may be spaced at an average spacing of at least 20 microns and less than or equal to 500 mm apart along a longitudinal axis of the second fluidic channel.

11. The method as in claim 1 , comprising flowing the fluid comprising the first group of the plurality of particles and a second group of the plurality of particles in the first fluidic channel, wherein a difference in pressure between the first fluidic channel and the second fluidic channel results in at least a second particle from the second group entering the second fluidic channel, wherein particles within the second fluidic channel may be separated such that at least 90% of the spacings between particles in the second fluidic channel differ by no more than less than 10% and greater than or equal to 0.1% of an average spacing between the particles.

12. The method as in claim 1 , comprising flowing the fluid comprising the first group of the plurality of particles and a second group of the plurality of particles in the first fluidic channel, wherein a difference in pressure between the first fluidic channel and the second fluidic channel results in at least a second particle from the second group entering the second fluidic channel, wherein an average velocity of the particles within the second fluidic channel along the longitudinal axis of the second fluidic channel is greater than or equal to 0.1 mm/second and less than or equal to 10 mm/second.

13. The method as in claim 1 , comprising flowing the fluid comprising the first group of the plurality of particles and a second group of the plurality of particles in the first fluidic channel, wherein a difference in pressure between the first fluidic channel and the second fluidic channel results in at least a second particle from the second group entering the second fluidic channel, wherein each particle enters the second fluidic channel from the first fluidic channel at a frequency of less than or equal to 1 particle per 10 seconds and greater than or equal to 1 particle per 120 seconds.

14. The method as in claim 1 , wherein the second fluidic channel is in fluidic communication with at least one suspended microchannel resonator.

15. The method as in claim 1 , comprising, flowing at least a portion of a fluid in which the single particle is suspended, out of the second fluidic channel and into the first fluidic channel, while maintaining the single particle in the second fluidic channel.

16. The method as in claim 1 , wherein the detector is selected from the group consisting of optical detectors, mass sensors, capacitive sensors, thermal sensors, resistive pulse sensors, electrical current sensors, MEMS-based pressure sensors, acoustic sensors, ultrasonic sensors and suspended microchannel resonators.

17. A method, comprising:
introducing a single particle into a second fluidic channel from a first fluidic channel containing a plurality of particles in a fluid, the second fluidic channel in fluidic communication with the first fluidic channel, wherein a difference in pressure between the first fluidic channel and the second fluidic channel results in the single particle entering the second fluidic channel;
detecting, with a detector, the presence of the single particle in the second fluidic channel; and
responsive to detecting the single particle, retaining the single particle at a constant flow rate through the second fluidic channel while changing a flow rate of the remaining particles from the plurality of particles through the first fluidic channel such that no additional particles from the plurality of particles enter into the second fluidic channel.

18. A method, comprising:
introducing a plurality of particles in a fluid into a first fluidic channel;
flowing a first group of particles from the plurality of particles in the first fluidic channel, wherein a difference in pressure between the first fluidic channel and a second fluidic channel results in a first particle from the first group of particles entering the second fluidic channel while the remaining particles in the first group of particles do not enter the second fluidic channel;
changing a flow rate of the fluid in the first fluidic channel;
flowing a second group of particles from the plurality of particles in the first fluidic channel, wherein a difference in pressure

Assignees

• Massachusetts Inst Technology

Inventors

• Kimmerling Robert J
• Calistri Nicholas L
• Manalis Scott R
• Olcum Selim
• Stevens Mark M

Classifications

• G01N2015/0288

  Sorting the particles · CPC title

• G01N15/0205

  by optical means · CPC title

• G01N2015/1006

  for cytology · CPC title

• B01L2300/0864

  comprising only one inlet and multiple receiving wells, e.g. for separation, splitting · CPC title

• B01L2300/0663

  Whole sensors · CPC title