Hydrodynamic capture and release mechanisms for particle manipulation
First Claim
1. A cell manipulation apparatus comprising:
- an array of sites arranged across a substrate in a pattern, each site configured to hold one cell, wherein each site further comprises;
a cell capture mechanism associated with each site that is capable of capturing the cell, and a cell release mechanism comprising at least one microbubble actuator for selectively releasing the cell from the site.
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Abstract
A cell analysis and sorting apparatus is capable of monitoring over time the behavior of each cell in a large population of cells. The cell analysis and sorting apparatus contains individually addressable cell locations. Each location is capable of capturing and holding a specified number of cells, and selectively releasing that specified number of cells from that particular location. In one aspect of the invention, the cells are captured and held in wells, and released using vapor bubbles as a means of cell actuation. Disclosed are: a cell manipulation apparatus design; various resistive heater configurations for nucleating microbubbles; various well designs, each in communication with a nucleation chamber or channel, for capturing a specified number of cells; and methods of fabrication and cell population manipulation.
146 Citations
69 Claims
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1. A cell manipulation apparatus comprising:
an array of sites arranged across a substrate in a pattern, each site configured to hold one cell, wherein each site further comprises;
a cell capture mechanism associated with each site that is capable of capturing the cell, and a cell release mechanism comprising at least one microbubble actuator for selectively releasing the cell from the site. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 40, 41)
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38-39. -39. (canceled)
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42. A method of making a cell manipulating apparatus, comprising the steps of:
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forming a well on one surface of a substrate, the well being configured and dimensioned to hold one cell;
forming a bubble nucleation chamber on the same substrate or a second substrate;
forming a channel on the same substrate or the second substrate to connect the well and chamber together and permit fluid communication therebetween; and
coupling a heating element to the bubble nucleation chamber. - View Dependent Claims (43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64)
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65. A method for manipulating a cell population, the method comprising:
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providing a cell manipulation apparatus with an array of sites across at least one substrate in a pattern, each site configured to hold one cell, and each site including a capture mechanism capable of capturing one cell and a release mechanism comprising at least one microbubble actuator for selectively releasing the cell from the site, introducing a fluid medium containing a plurality of cells onto the apparatus, capturing a cell in at least one well, assessing at least one property of the captured cell, and selectively releasing the captured cell based on the assessment. - View Dependent Claims (66, 67, 68, 69)
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Specification