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US 12,723,228 B2Granted
Differential flow micro-valve sampling in integrated sensor platform for cell or tissue culture and analysis
AssigneeColorado State University Research Foundation
InventorThomas Chen
Life of this patent
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Abstract
Electrochemical sensing devices and methods of using thereof employs a set of one or more sensor-integrated sampling wells or containers that operates with a pressure differential micro-valve to move controlled volume of sampled fluid within a controlled cell-growing environment. The differential micro-valve can be integrated into an instrumented well having one or more sensors to provide a high-throughput smart well plate platform for use in automation operation in diagnostics and drug discovery.
Claims21
An electrochemical sensing device comprising:
- one or more substrates joined to form:
- a culture container configured to retain an electrochemical sample, the one or more substrates forming a bottom surface and a side wall surface for the culture container that terminates at a top to define the culture container;
- a set of two or more sample containers in operative connection with the culture container through a set of respective channels defined in the one or more substrates, the one or more substrates forming a second bottom surface and a second side wall surface that terminates at a second top to define each of the sample containers, wherein each of the first set of channels has a cross-sectional area at a first end that expands to form each respective sample container and has a cross-sectional area at a second end that expands to form the culture container;
- a port in operative connection with the sample containers through a second set of channels defined in the one or more substrates,
- wherein the first set of channels and the second set of channels are interconnected through the sample container and the culture container to form a differential micro-valve controlled by application of differential pressure and without mechanical moving parts in the channels;
- and
- a controller configured to generate a first command to control application of the differential pressure and initiate an analysis sequence of the electrochemical sample;
- wherein the controller is configured to control the actuation of a pump to apply a single negative pressure at the port to induce a first pressure differential along a path defined between the first set of channels, through the set of two or more sample containers, to the second set of channels, to cause a portion of the electrochemical sample to flow from the culture container through the first set of channels to the two or more sample containers,
- wherein the set of two or more sample containers are instrumented to conduct electrochemical analyses of the electrochemical sample and provide signals corresponding to measurements of electrochemical analyses of the electrochemical sample to the controller, and
- wherein, subsequent to the measurements, the controller is configured to generate a second command to control the actuation of a pump to induce a second pressure differential along the path defined between the first set of channels and the second set of channels to clear the sample container.
7 more elements
A method of detecting culture parameters comprising:
- providing an electrochemical sensing device comprising:
- one or more substrates joined to form:
- a culture container configured to retain an electrochemical sample, the one or more substrates forming a bottom surface and a side wall surface for the culture container that terminates at a top to define the culture container;
- a set of two or more sample containers in operative connection with the culture container through a set of respective channels defined in the one or more substrates, the one or more substrates forming a second bottom surface and a second side wall surface that terminates at a second top to define each of the sample containers, wherein each of the first set of channels has a cross-sectional area at a first end that expands to form each respective sample container and has a cross-sectional area at a second end that expands to form the culture container;
- a port in operative connection with the sample container through a second set of channels defined in the one or more substrates,
- wherein the first set of channels and the second set of channels are interconnected through the sample container and the culture container to form a differential micro-valve controlled by application of differential pressure and without mechanical moving parts in the channels;
- and
- a controller configured to generate a first command to control application of the differential pressure and initiate an analysis sequence of the electrochemical sample;
- wherein the controller is configured to control the actuation of a pump to apply a single negative pressure at the port to induce a first pressure differential along a path defined between the first set of channels, through the set of two or more sample containers, to the second set of channels, to cause a portion of the electrochemical sample to flow from the culture container through the first set of channels to the two or more sample containers,
- culturing a cell, tissue, organ, or a combination thereof in the culture container;
- acquiring signals from at least one sensor or electrode located in proximity to, or in, the two or more sample containers, wherein the signals are subsequently analyzed to assess the culture parameters;
- and
- providing to the controller the acquired signals corresponding to measurements of electrochemical analyses of the electrochemical sample,
- wherein, subsequent to the measurements, the controller is configured to generate a second command to control the actuation of a pump to induce a second pressure differential along the path defined between the first set of channels and the second set of channels to clear the sample container.
11 more elements
Dependencies are inferred from the claim text.