Method and Microfluidic Device for Studying Cell Deformations
US-2024210301-A1 · Jun 27, 2024 · US
US10488320B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-10488320-B2 |
| Application number | US-201414579441-A |
| Country | US |
| Kind code | B2 |
| Filing date | Dec 22, 2014 |
| Priority date | Jul 16, 2013 |
| Publication date | Nov 26, 2019 |
| Grant date | Nov 26, 2019 |
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A microfluidic chip orients and isolates components in a sample fluid mixture by two-step focusing, where sheath fluids compress the sample fluid mixture in a sample input channel in one direction, such that the sample fluid mixture becomes a narrower stream bounded by the sheath fluids, and by having the sheath fluids compress the sample fluid mixture in a second direction further downstream, such that the components are compressed and oriented in a selected direction to pass through an interrogation chamber in single file formation for identification and separation by various methods. The isolation mechanism utilizes external, stacked piezoelectric actuator assemblies disposed on a microfluidic chip holder, or piezoelectric actuator assemblies on-chip, so that the actuator assemblies are triggered by an electronic signal to actuate jet chambers on either side of the sample input channel, to jet selected components in the sample input channel into one of the output channels.
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What is claimed is: 1. A microfluidic chip system in conjunction with selected and/or unselected components, comprising: a sample input channel into which a sample fluid mixture of the selected and/or unselected components is inputted; a first plurality of sheath fluid channels into which sheath fluids are inputted, said first plurality of sheath fluid channels which intersect said sample input channel at a first intersection in a first plane; a second plurality of sheath fluid channels, into which sheath fluids are inputted, said second plurality of sheath fluid channels which intersect from above and below said sample input channel at a second intersection in a vertical second plane downstream from the first intersection; wherein at least a portion of said second plurality of sheath fluid channels which intersect said sample input channel is at substantially a 90 degree angle relative to said sample input channel; wherein the first plane is different from the vertical second plane; wherein said first plurality of sheath fluid channels and said second plurality of sheath fluid channels compress said components in said sample fluid mixture such that said components are oriented in a predetermined direction in said sample fluid channel; an interrogation apparatus which interrogates and identifies said selected and/or unselected components in said fluid mixture, as said selected and/or unselected components flow through an interrogation chamber disposed in said sample fluid channel, said interrogation chamber located downstream from said second intersection; a focused energy device which emits a focused energy beam which kills said selected components in said sample fluid mixture; and at least one output channel at one end of the sample input channel, downstream from said interrogation chamber, said at least one output channel through which both the killed, selected components and the unselected components exit. 2. The microfluidic chip system according to claim 1 , wherein said interrogation chamber comprises: an opening cut through a structural layer in the microfluidic chip, through which said focused energy beam passes to reach said selected components. 3. The microfluidic chip system according to claim 2 , further comprising: a computer which displays said components in a field of view acquired by a CCD camera disposed over said opening in the micro fluidic chip. 4. The microfluidic chip system according to claim 1 , wherein said interrogation apparatus comprises: a light source configured to emit a light beam which illuminates and excites said components in said sample fluid mixture. 5. The microfluidic chip system according to claim 1 , further comprising: a pumping mechanism which pumps said sample fluid from a reservoir into said sample input of said microfluidic chip, and pumps said sheath fluids into sheath inputs of said first and said second plurality of sheath fluid channels. 6. The microfluidic chip system according to claim 5 , further comprising: a computer which controls pumping of said one of said sample fluid mixture or said sheath fluids into the microfluidic chip. 7. The microfluidic chip system according to claim 6 , further comprising: a computer which displays said components in a field of view acquired by a CCD camera disposed over the microfluidic chip. 8. The microfluidic chip system according to claim 1 , wherein said components are cells. 9. The microfluidic chip system according to claim 8 , wherein said cells include at least one of viable and motile sperm from non-viable or non-motile sperm; sperm distinguished by gender and other sex sorting variations; stem cells distinguished from cells in a population; one or more labeled cells distinguished from un-labeled cells including sperm cells; cells, including sperm cells, distinguished by desirable or undesirable traits; genes distinguished in nuclear DNA according to a specified characteristic; cells distinguished based on surface markers; cells distinguished based on membrane integrity or viability; cells distinguished based on potential or predicted reproductive status; cells distinguished based on an ability to survive freezing; cells distinguished from contaminants or debris; healthy cells distinguished from damaged cells; red blood cells distinguished from white blood cells and platelets in a plasma mixture; or any cells distinguished from any other cellular components into corresponding fractions. 10. A method of distinguishing components in a fluid mixture, comprising: inputting a sample fluid mixture containing components into a sample input channel of a microfluidic chip; inputting sheath fluids into a plurality of first sheath fluid channels of the microfluidic chip, the sheath fluids from the plurality of first sheath fluid channels which join the sample fluid mixture in the sample input channel at a first intersection between the plurality of first sheath fluid channels and the sample input channel in a horizontal plane; compressing the sample fluid mixture on all sides in a horizontal direction and a vertical direction with the sheath fluids from the plurality of first sheath fluid channels to focus the components in the sample fluid mixture to a center of said sample input channel; and inputting sheath fluids into a plurality of second sheath fluid channels of the microfluidic chip, the sheath fluids from the plurality of second sheath fluid channels which join the sample fluid mixture in the sample input channel from above and below at a second intersection between the plurality of second sheath fluid channels and the sample input channel, downstream from the first intersection, wherein the plurality of second sheath fluid channels intersect the sample input channel at the second intersection in a vertical plane above and below the sample input channel and wherein at least a portion of said second plurality of sheath fluid channels which intersect said sample input channel is at substantially a 90 degree angle relative to said sample input channel; further compressing the sample fluid mixture at the second intersection in the vertical direction with the sheath fluids from the plurality of second sheath fluid channels, such that the components are focused and aligned in the center of the sample input channel as the components flow through the sample input channel; interrogating and identifying the components in the fluid mixture, as said components flow through an interrogation chamber disposed in said sample fluid channel, said interrogation chamber located downstream from said second intersection; killing selected components in the sample fluid mixture with a focused energy device which emits a focused energy beam; and exiting both selected components and the unselected components through at least one output channel at one end of the sample input channel, downstream from said interrogation chamber.
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