Microresonant sensors and methods of use thereof
First Claim
1. A method of monitoring density in a fluid, comprising:
- placing said fluid into contact with a micromechanical sensor assembly comprising a membrane having an upper surface facing toward said fluid and a lower surface facing away from said fluid, wherein said membrane vibrates in response to electrical current; and
monitoring a vibrational frequency of said membrane, wherein said vibrational frequency is related to density of a volume of said fluid at or near said membrane upper surface.
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Accused Products
Abstract
A sensor assembly for sensors such as microfabricated resonant sensors is disclosed. The disclosed assembly provides improved performance of the sensors by providing a thermally insensitive environment and short pathways for signals to travel to processing components. Further, the assembly provide modular construction for the sensors and housing modules, thereby allowing replacement of the sensors at a lower cost. The assembly includes a sensor module including a sensor formed on a conductive substrate with a cavity formed on one surface. The substrate has conductive vias extending from the cavity to a second surface of the substrate. A housing assembly accommodates the sensor and includes a rigid housing, preferably made from a ceramic. An electronic component, such as an amplifier, is mounted on the rigid housing. The electronic component electrically engages the vias substantially at the second surface of the substrate. The electronic component receive signals from the sensor through the vias. The signals are then processed through an amplifier and a digital signal processor using a modified periodogram.
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Citations
35 Claims
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1. A method of monitoring density in a fluid, comprising:
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placing said fluid into contact with a micromechanical sensor assembly comprising a membrane having an upper surface facing toward said fluid and a lower surface facing away from said fluid, wherein said membrane vibrates in response to electrical current; and
monitoring a vibrational frequency of said membrane, wherein said vibrational frequency is related to density of a volume of said fluid at or near said membrane upper surface. - 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)
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27. A method of screening a library of test molecules for the ability to bind to a population of cells, comprising:
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contacting an array comprising a plurality of discretely addressable micromechanical sensor assembly sites with said population of cells, wherein each site comprises a membrane having an upper surface facing toward an aqueous liquid environment comprising said population of cells and a lower surface facing away from said aqueous liquid environment, wherein said membrane vibrates in response to electrical current, and wherein each of said plurality of micromechanical sensor assembly sites comprise one or more test molecules from said library directly or indirectly affixed to said membrane upper surface; and
determining whether a change in vibrational frequency of said membrane occurs at each of said plurality of micromechanical sensor assembly sites, wherein said vibrational frequency at each individual micromechanical sensor assembly site is related to binding of one or more cells to said one or more test molecules affixed at said individual micromechanical sensor assembly site. - View Dependent Claims (28, 29)
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30. A method of screening a library of test molecules for the ability to inhibit binding of a ligand to a cell surface molecule, comprising:
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contacting an array comprising a plurality of discretely addressable micromechanical sensor assembly sites with a population of cells expressing said cell surface molecule and one or more test molecules, wherein each site comprises a membrane having an upper surface facing toward an aqueous liquid environment comprising said population of cells and a lower surface facing away from said aqueous liquid environment, wherein said membrane vibrates in response to electrical current, and wherein each of said plurality of micromechanical sensor assembly sites comprise said ligand directly or indirectly affixed to said membrane upper surface, and wherein each discretely addressable micromechanical sensor assembly site is contacted with different test molecules; and
determining whether a change in vibrational frequency of said membrane occurs at each of said plurality of micromechanical sensor assembly sites, wherein said vibrational frequency at each individual micromechanical sensor assembly site is related to binding of one or more cells to said ligand affixed at said individual micromechanical sensor assembly site. - View Dependent Claims (31, 32, 33, 34, 35)
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30-1. A method of sorting cells in a cell population according to the expression of a plurality of cell surface molecules on said cells, comprising:
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contacting a sensor array with one or more test molecules that bind one or more cell surface molecules on one or more cells in the cell population, wherein said sensor array comprises (i) a plurality of discretely addressable micromechanical sensor assembly sites, each site comprising a micromechanical sensor assembly comprising a membrane having an upper surface facing toward an aqueous environment and a lower surface facing away from said fluid, wherein said membrane vibrates in response to electrical current, wherein a vibrational frequency of said membrane is related to density of a volume of said fluid at or near said membrane upper surface, and (ii) one or more cells from said cell population bound to an immobilized receptor for a cell surface molecule, thereby immobilizing said one or more cells within the sensed volume of each of said plurality of discretely addressable micromechanical sensor assembly sites; and
monitoring a change in vibrational frequency of said membrane at each site resulting from one or more test molecules binding to said one or more cells within the sensed volume at each site.
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Specification