High throughput methods, systems and apparatus for performing cell based screening assays
DCFirst Claim
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1. A computer implemented method of determining a level of function of cells, comprising:
- receiving first signals corresponding to a first detectable property of the cells in a suspension flowing along a fluid channel;
receiving second signals corresponding to a second detectable property produced by the cells upon activation of the function of the cells; and
determining the level of the function of the cells by comparing the first and second signals.
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Abstract
Methods for determining a function of cells, which comprises a suspension of cells flowing along a first fluid channel. The cells have a first detectable property associated therewith, and wherein the cells produce a second detectable property upon activation of the function of the cells, the first and second detectable properties being distinguishable from each other. Levels of the first and second detectable properties are measured. The level of the second detectable property is compared to the level of first detectable property to determine the relative function of the cells.
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Citations
42 Claims
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1. A computer implemented method of determining a level of function of cells, comprising:
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receiving first signals corresponding to a first detectable property of the cells in a suspension flowing along a fluid channel;
receiving second signals corresponding to a second detectable property produced by the cells upon activation of the function of the cells; and
determining the level of the function of the cells by comparing the first and second signals. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18)
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19. A computer program product for determining a level of function of cells, comprising:
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computer code that receives first signals corresponding to a first detectable property of the cells in a suspension flowing along a fluid channel;
computer code that receives second signals corresponding to a second detectable property produced by the cells upon activation of the function of the cells;
computer code that determines the level of the function of the cells by comparing the first and second signals; and
a computer readable medium that stores the computer codes. - View Dependent Claims (20)
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21. A system, comprising:
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a microfluidic device having a fluid channel;
at least one detector for measuring at least one detectable property in the fluid channel; and
a computer system that controls the flow of a suspension of cells along the fluid channel and receives signals from the at least one detector, the computer system executing a program stored on a computer readable medium comprising;
computer code that receives first signals corresponding to a first detectable property of the cells in a suspension flowing along a fluid channel;
computer code that receives second signals corresponding to a second detectable property produced by the cells upon activation of the function of the cells; and
computer code that determines the level of the function of the cells by comparing the first and second signals. - View Dependent Claims (22)
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23. A computer implemented method of determining a binding function of cells, comprising:
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receiving first signals corresponding to a detectable property of the cells in a suspension flowing along a binding region of a fluid channel in the presence of a test compound, the binding region having a binding moiety immobilized on an interior surface of the fluid channel and the cells including on their surfaces a moiety bound by the binding moiety;
calculating a velocity of the cells flowing through the binding region by analyzing the first signals; and
determining an effect of the test compound on the binding function of the cells by comparing the velocity to a reference velocity. - View Dependent Claims (24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38)
receiving second signals corresponding to the detectable property of the cells in the suspension flowing along the non-binding region of the fluid channel in the presence of the test compound; and
calculating the reference velocity by analyzing the second signals.
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27. The method of claim 23, further comprising flowing the suspension of cells along the fluid channel.
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28. The method of claim 27, wherein flowing the suspension of cells along the fluid channel includes pulsing groups of cells through the fluid channel.
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29. The method of claim 27, wherein flowing the suspension of cells along the fluid channel includes applying a pressure differential across the length of the fluid channel.
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30. The method of claim 29, wherein applying the pressure differential includes applying a hydrostatic pressure to one end of the fluid channel.
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31. The method of claim 29, wherein applying the pressure differential includes applying an electroosmotically driven pressure to one end of the fluid channel.
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32. The method of claim 23, wherein calculating a velocity of the cells flowing through the binding region includes:
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determining a time difference between when the first signals indicate the cells passed first and second points on the fluid channel, the first and second points being spaced apart along the fluid channel; and
calculating the velocity from the time difference and a distance along the fluid channel between the first and second points.
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33. The method of claim 23, further comprising introducing the test compound into the fluid channel.
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34. The method of claim 23, further comprising displaying the effect of the test compound on the binding function of the cells to a user.
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35. The method of claim 23, wherein the effect is that the test compound is an inhibitor of the binding function of the cells if the velocity is less than the reference velocity and the effect is that the test compound is an enhancer of the binding function of the cells if the velocity is less than the reference velocity.
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36. The method of claim 23, further comprising determining effects of a plurality of different test compounds on the binding function of the cells by analyzing velocities of cells flowing serially through the binding region in the presence of each of the different test compounds.
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37. The method of claim 36, further comprising displaying the effect of each of the different test compounds to a user.
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38. The method of claim 36, further comprising introducing the different test compounds serially into the fluid channel.
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39. A computer program product for determining a binding function of cells, comprising:
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computer code that receives first signals corresponding to a detectable property of the cells in a suspension flowing along a binding region of a fluid channel in the presence of a test compound, the binding region having a binding moiety immobilized on an interior surface of the fluid channel and the cells including on their surfaces a moiety bound by the binding moiety;
computer code that calculates a velocity of the cells flowing through the binding region by analyzing the first signals;
computer code that determines an effect of the test compound on the binding function of the cells by comparing the velocity to a reference velocity; and
a computer readable medium that stores the computer codes. - View Dependent Claims (40)
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41. A system, comprising:
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a microfluidic device having a fluid channel;
at least one detector for measuring at least one detectable property in the fluid channel; and
a computer system that controls the flow of a suspension of cells along the fluid channel and receives signals from the at least one detector, the computer system executing a program stored on a computer readable medium comprising;
computer code that receives first signals corresponding to a detectable property of the cells in a suspension flowing along a binding region of a fluid channel in the presence of a test compound, the binding region having a binding moiety immobilized on an interior surface of the fluid channel and the cells including on their surfaces a moiety bound by the binding moiety;
computer code that calculates a velocity of the cells flowing through the binding region by analyzing the first signals; and
computer code that determines an effect of the test compound on the binding function of the cells by comparing the velocity to a reference velocity. - View Dependent Claims (42)
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Specification