Apparatus and method for real-time measurement of cellular response
First Claim
1. An apparatus for automatically measuring the effect of a plurality of test compounds on living cells, comprising:
- a test compound sampler for sequentially and automatically providing samples of multiple test compounds;
a cell suspension source for providing a suspension of living cells;
a mixing chamber, coupled to the test compound sampler and the cell suspension source, for receiving the samples of the test compounds from the test compound sampler, receiving the suspension of living cells from the cell suspension source, and for mixing each test compound with the suspension of living cells so as to provide a respective test solution for each test compound;
a detector, coupled to the mixing chamber, for receiving each respective test solution and for measuring a cellular response of the suspended cells for each said test solution; and
a conduit establishing a flow channel between the mixing chamber and the detector, such that each said test solution flows from the mixing chamber to the detector.
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Abstract
An apparatus and method for real-time measurement of a cellular response of a test compound or series of test compounds on a flowing suspension of cells in which a homogeneous suspension of living cells is combined with a concentration of a test compound, directed through a detection zone, and a cellular response of the living cells is measured in real time as the cells in the test mixture are flowing through the detection zone. The apparatus may be used in automated screening of libraries of compounds, and is capable of real-time variation of concentrations of test and standard compounds and generation of dose/response profiles within a short timespan.
251 Citations
50 Claims
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1. An apparatus for automatically measuring the effect of a plurality of test compounds on living cells, comprising:
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a test compound sampler for sequentially and automatically providing samples of multiple test compounds; a cell suspension source for providing a suspension of living cells; a mixing chamber, coupled to the test compound sampler and the cell suspension source, for receiving the samples of the test compounds from the test compound sampler, receiving the suspension of living cells from the cell suspension source, and for mixing each test compound with the suspension of living cells so as to provide a respective test solution for each test compound; a detector, coupled to the mixing chamber, for receiving each respective test solution and for measuring a cellular response of the suspended cells for each said test solution; and a conduit establishing a flow channel between the mixing chamber and the detector, such that each said test solution flows from the mixing chamber to the detector. - 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, 38)
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39. An apparatus for measuring the effect of a test compound on living cells, comprising:
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a test compound source; a cell suspension reservoir providing a suspension of living cells; a first channel, coupled to the test compound source, through which the test compound can flow; a second channel, coupled to the cell suspension source, through which the suspension of living cells can flow; a mixing zone, coupled to the first and second channels, so that the test compound and cell suspension can flow into the mixing zone to provide a desired mixture of the test compound and the cell suspension in said mixing zone; a fluid flow path through which said mixture can flow from the mixing zone; and a detector, coupled to the fluid flow path, which measures a cellular response of the suspended cells to the test compound, wherein the desired mixture of the test compound and the cell suspension flows along the fluid flow path from the mixing chamber to the detector. - View Dependent Claims (40, 41, 42, 43, 44)
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45. An apparatus for measuring the effect of a test compound on living cells, comprising:
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a test compound source; a first gradient device, coupled to the test compound source, for automatically adjusting the concentration level of a test compound transferred to said mixing chamber from said test compound source; a cell suspension source; a mixing chamber, coupled to the first gradient device and the cell suspension source, which receives the test compound and a suspension of living cells from the cell suspension source and mixes the test compound with the suspension of living cells; and a detector, coupled to the mixing chamber, for measuring a cellular response of the suspended cells to the test compound. - View Dependent Claims (46, 47, 48, 49, 50)
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Specification