Micro-pore Array for High-throughput Cell Screening
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Solution Overview
Problem
Current high-throughput assay screening technologies lack robustness and selectivity for large-scale diagnostic and therapeutic applications, particularly in selecting and characterizing specific interaction pairs from heterogeneous cell populations, due to limitations in existing display systems like phage display, ribosome display, and microengraving.
Innovation Solution
A high-density micro-pore array system where a micro-pore array is reversibly attached to a solid substrate, allowing for the screening and collection of cells from selected micro-pores, enabling direct selection and characterization of specific interaction pairs without the need for display on viruses or cells, with the array comprising micro-pores with diameters ranging from 1.0 micrometers to 500 micrometers and a pressure source for cell collection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If display systems like phage display, ribosome display, or microengraving are used for screening, then cell selection capability is provided, but robustness and selectivity for large-scale applications are insufficient
Solution Approach 1:
The invention segments the screening process into distinct functional components: a micro-pore array for parallel cell containment, a solid substrate for binding partner presentation, and a pressure source for selective cell ejection. This segmentation allows each component to be optimized independently, achieving both high reliability in cell selection and high productivity in large-scale screening of billions of cells.
Solution Approach 2:
The micro-pore array serves as an intermediary device that bridges the solid substrate (with binding partners) and the cell suspension. It enables parallel interaction assays between billions of cells and binding partners while maintaining individual cell containment, thereby achieving both selectivity through specific binding events and productivity through massive parallelization.
2Stability of the object's composition
If micro-pore array is permanently attached to substrate, then structural stability is improved, but cell collection from selected micro-pores becomes difficult
Solution Approach 1:
The attachment between micro-pore array and solid substrate is made dynamic rather than static. The array can be reversibly attached during the screening phase to maintain structural stability, then easily detached for cell collection. This dynamic attachment enables the system to switch between stable operation mode and easy cell recovery mode.
Solution Approach 2:
A pressure source is introduced to apply controlled pressure to the micro-pore array, enabling selective ejection of cells from identified micro-pores onto a collection surface. This pneumatic mechanism facilitates easy cell collection while maintaining the array's structural integrity during the screening process.
3Productivity
If high-density micro-pore array is used for parallel screening, then productivity is improved, but device complexity increases
Solution Approach 1:
The micro-pore array is designed as a universal platform that can screen billions of cells in parallel using the same basic structure and protocol. The system handles diverse cell types and binding partners through a standardized interface, achieving high productivity without proportionally increasing device complexity. The pressure source and collection mechanism are also multi-functional, serving both cell ejection and potential cell manipulation purposes.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach allows for the efficient and selective isolation of specific cells or compounds from large populations, reducing non-specific binding and enabling rapid analysis of billions of cells in parallel, with improved specificity and reduced assay time, overcoming the limitations of existing methods.
Implementation Method 1
a micro-pore array is reversibly attached to a solid substrate
Implementation Method 2
applying pressure to the micro-pore array with a pressure source
Data Source
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AI summary
The present invention describes a spatial addressing technique that uses a very high-density micro-pore array for high-throughput screening of biological interactions. The therapeutic, diagnostic and drug-discovery implications of being able to identify, select and characterize specific protein-protein, protein-DNA and/or protein-carbohydrate interactions from heterogeneous populations of millions (to billions) of cells is discussed. Importantly, this technique possesses the screening and selection capacity of current display-based screening systems (i.e. millions-billions) but with greater efficiency and shorter time.