Layered structure for improved sealing of microwell arrays
Inventors
Anderson, Clifford • Lee, Kristen • Messner, Jacob • Kelbauskas, Laimonas • Ueberroth, Benjamin • Tian, Yanqing • Meldrum, Deirdre
Assignees
Arizona State University ASU • Arizona State University Downtown Phoenix campus
Publication Number
US-11369966-B2
Publication Date
2022-06-28
Expiration Date
2036-09-16
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Abstract
A multi-layer sealing structure for sealing a microwell array defined in or on a substrate includes at least one front compliant layer, a back compliant layer, and a flexural layer arranged between the at least one front compliant layer and the back compliant layer, wherein the at least one front compliant layer is closer than the back compliant layer to microwells of the microwell array. One or more front compliant layers may be optically reflective and/or may embody a sensor layer. The back compliant layer may include an adhesive or various types of rubber, and the flexural layer may include a polymeric material or metal. A multi-layer sealing structure may be separated from a microwell array by peeling. A multi-layer sealing structure allows local disruption of sealing where particle contaminants are present without compromising the sealing performance of an entire microwell array, and without requiring a large sealing force.
Core Innovation
The invention relates to a multi-layer sealing structure for sealing a microwell array defined in or on a substrate, especially for use in the analysis of single living cells or discrete groups of living cells. The structure includes at least one front compliant layer, a back compliant layer, and a flexural layer arranged between the two, wherein the front compliant layer is closer to the microwells. In certain embodiments, the front compliant layer may be optically reflective, may comprise aluminum, and may include or embody a sensor layer.
The problem addressed by the invention is the inability of conventional sealing structures to reliably seal microwell arrays in the presence of particulate contamination, especially small microscopic particles that are difficult to remove or detect. Existing methods either require excessive sealing force, which can affect cell viability, or are not compatible with measurements of single or small numbers of living cells. The art seeks improved structures that tolerate microscopic contaminants without compromising the sealing performance of the microwell array and without requiring a large sealing force.
This multi-layer sealing structure can be removed from the microwell array by peeling, allowing local disruption of sealing where particle contaminants exist, without affecting the performance of the entire array. Additionally, certain embodiments allow for integration of sensor layers and optical reflectivity to enhance analysis capabilities, improve the handling during fabrication, and maintain a robust, cost-effective sealing solution.
Claims Coverage
The patent includes three independent claims, each describing a core inventive feature covering the composition, device, and method aspects of the invention.
Multi-layer sealing structure with optically reflective front compliant layer
A sealing structure for microwell arrays comprising at least one front compliant layer, a back compliant layer, and a flexural layer positioned between these two, where the entire front compliant layer is closer to the substrate than the back compliant layer, and the entirety of the surface of the front compliant layer is optically reflective.
Microfluidic device comprising the multi-layer sealing structure
A microfluidic device includes a substrate that defines a microwell array, with the above-described multi-layer sealing structure arranged to seal the microwell array.
Method for arranging cellular material with multi-layer sealing structure
A method involving arranging cells or groups of cells in microwells of a microwell array with raised lips, and applying the multi-layer sealing structure over the raised lips to seal the cells or groups of cells within the microwells.
The inventive features provide a multi-layer sealing structure with an optically reflective compliant layer, its use within microfluidic devices, and methods for sealing microwell arrays containing biological material.
Stated Advantages
Allows local disruption of sealing where particle contaminants are present without compromising the sealing performance of the entire microwell array.
Does not require a large sealing force, making it suitable for live cell applications.
Is tolerant to microscopic particle contamination on microwell surfaces.
Is robust to handling during fabrication, such as during sensor deposition.
Is low in cost and compatible with inclusion of sensing capabilities and optical reflectivity.
The sealing structure can be removed by peeling, which improves cell retention and enables repeated assays on the same cells under different conditions.
Documented Applications
Use in microfluidic devices for analyzing single living cells or discrete groups of living cells.
Sealing microwell arrays in assays requiring the measurement of live-cell metabolism, including detection of analytes like oxygen concentration and pH.
Enabling repeated assay tests on the same cells under varying conditions such as drug treatment by allowing removal and resealing of the structure.
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