Mesoscale devices and methods for analysis of motile cells
First Claim
1. A method of analyzing a fluid sample having cells characterized by their motility, comprising:
- a) providing a device comprising;
a solid substrate having a flow system which comprises at least one elongate flow channel of mesoscale cross-sectional dimension, and a receiving well communicating with said at least one channel and defining a starting point in said channel; and
a cover for said substrate closing said channel and having a first port in registry with said receiving well, for introducing said sample into said receiving well so as to enable the motile cells of the sample to travel from the receiving well to progress points along the at least one channel, said cover further defining a second port in registry with said at least one channel at a point therealong, said flow system being filled with a carrier fluid;
b) introducing said sample into said receiving well;
c) controlling the resident conditions of the combined carrier fluid and sample to assure motility of said cells in said carrier fluid;
d) observing the cells in the flow system;
e) collecting data based on said observation; and
f) completing the analysis using said data.
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Accused Products
Abstract
Devices and methods are provided to facilitate the rapid, accurate analysis of a sample having cells characterized by their motility. The devices feature a solid substrate microfabricated to define a flow system including one or more ports or chambers, connected by elongate channels of various shapes having a mescoscale cross-sectional dimension on the order of 0.1 μm to 1000 μm. In one embodiment, the devices are fitted with various flow-regulating features to facilitate unimpeded movement of the motile cells of interest along the flow channels. In another embodiment, devices are provided for conducting replicate motile cell assays, or for conducting a series of different assays using a single test sample. In another embodiment, preparative devices are provided for separating and collecting selected motile cell types of interest. In another embodiment, a device designed for performing an in vitro fertilization is provided in a portable incubator, which maintains the in vitro fertilization under optimum conditions. The devices of the invention may be used in a wide range of applications, and are particularly applicable for analyses and preparation of sperm, as well as in vitro fertilization. The devices and methods of the invention are also suitable for various analyses of a wide variety of motile cells, such as motile microorganisms and chemotactic cells, and can be used in clinical tests as well as laboratory and field tests.
560 Citations
13 Claims
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1. A method of analyzing a fluid sample having cells characterized by their motility, comprising:
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a) providing a device comprising; a solid substrate having a flow system which comprises at least one elongate flow channel of mesoscale cross-sectional dimension, and a receiving well communicating with said at least one channel and defining a starting point in said channel; and a cover for said substrate closing said channel and having a first port in registry with said receiving well, for introducing said sample into said receiving well so as to enable the motile cells of the sample to travel from the receiving well to progress points along the at least one channel, said cover further defining a second port in registry with said at least one channel at a point therealong, said flow system being filled with a carrier fluid; b) introducing said sample into said receiving well; c) controlling the resident conditions of the combined carrier fluid and sample to assure motility of said cells in said carrier fluid; d) observing the cells in the flow system; e) collecting data based on said observation; and f) completing the analysis using said data. - View Dependent Claims (2, 3, 5, 6, 7, 8, 9, 10)
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11. A method of performing an in vitro fertilization, comprising:
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a) providing a device comprising; a solid substrate having at least one elongate flow channel of mesoscale cross-sectional dimension; a receiving well communicating with said at least one channel and defining a starting point in said at least one channel; an egg nesting well communicating with said at least one channel and defining a terminating point in said at least one channel; and a cover for said substrate closing said at least one channel and having a first port for introducing a sperm sample into said receiving well to enable said sperm to travel from said receiving well through said at least one channel to said egg nesting well, said cover further comprising a second port in registry with said egg nesting well, said device containing in vitro fertilization medium; b) introducing at least one egg into said egg nesting well; c) introducing a sperm sample into said receiving well; and d) placing said device into a portable, sealable, environmental control chamber for a time and under conditions effective to enable said sperm to travel to said egg and to fertilize said egg. - View Dependent Claims (4, 12)
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13. A device for analyzing a sample having cells characterized by their motility, the device comprising:
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a solid substrate having a flow system which comprises at least one elongate flow channel of mesoscale cross-sectional dimension, and a receiving well communicating with said at least one channel and defining a starting point in said at least one channel, said at least one channel comprising a selection region, said selection region being adapted for selective separation of at least one motile cell type from a mixed population of cell types and comprising an electric field which selectively influences motility of said at least one motile cell type; and a cover for said substrate closing said at least one channel and having a first port in registry with said receiving well, for introducing a sample containing motile cells into said receiving well so as to enable the motile cells of the sample to travel from the receiving well to progress points along the channel, said cover defining a second port to said at least one channel at a point therealong.
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Specification