Bioprinting Cells on Patterned Adhesive-Repulsive Substrates
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Solution Overview
Problem
The current fabrication of biological microelectromechanical systems (bioMEMs) results in significant cell loss due to cells not adhering to substrates or adhering in unintended locations, leading to wastage and increased costs associated with cell culture.
Innovation Solution
A bioprinting method that uses advanced surface chemistry and precise cell patterning techniques to print cells onto substrates with defined adhesive and repulsive regions, allowing for high-resolution, efficient placement of cells on microelectrode arrays and cantilevers without the need for hydrogels, thereby minimizing cell wastage and optimizing cell culture conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If traditional hand plating methods are used to plate cells onto substrates, then cells can be placed on the substrate, but significant cell loss occurs due to cells not adhering or adhering in unintended locations
Solution Approach 1:
The substrate surface is divided into distinct regions with different properties: cell adhesive regions (with high cell adhesion) and cell repulsive regions (with low cell adhesion). This local differentiation ensures cells adhere only where intended, eliminating wasted cells that fail to adhere or adhere in unintended locations.
Solution Approach 2:
The substrate is pre-patterned with cell adhesive and cell repulsive regions before cell plating. This preliminary surface preparation creates predetermined adhesion zones that guide cell placement, ensuring high precision cell positioning while minimizing cell loss during the subsequent plating process.
2Productivity
If cells are plated onto entire substrate surfaces, then cells can be placed, but cells adhere in locations not measured by sensors resulting in wasted cells
Solution Approach 1:
The substrate surface is segmented into cell adhesive regions positioned over sensor areas and cell repulsive regions in non-sensor areas. This local property differentiation ensures cells are directed only to sensor-measured regions, maximizing cell culture efficiency while eliminating wastage in unmonitored areas.
Solution Approach 2:
Cell adhesive and cell repulsive regions act as intermediary surface modifications that mediate between the cell suspension and the substrate. These intermediate layers guide cell attachment behavior, ensuring cells selectively adhere to sensor regions while being repelled from non-sensor regions, thereby preventing cell wastage.
3Reliability
If conventional cell plating is used, then cells can be placed on substrates, but high cost and extensive time are associated with cell culture
Solution Approach 1:
The substrate surface is pre-patterned with cell adhesive and cell repulsive regions before cell plating. This preliminary action creates ready-to-receive cell zones, eliminating the need for extended cell culture time to achieve proper adhesion patterns, thereby reducing overall experiment duration while maintaining reliable cell adhesion.
Solution Approach 2:
By creating local adhesion zones through surface patterning, cells rapidly attach to designated areas without requiring extended culture periods. This localized approach ensures reliable adhesion is achieved quickly, reducing the extensive time typically needed for conventional cell culture while maintaining high adhesion reliability.
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 method achieves high cell survivability and functionality, reducing the number of cells required by up to 80-90% compared to traditional hand plating, while maintaining precise cell positioning and promoting long-term cell confinement on substrates, thus enhancing the efficiency and cost-effectiveness of bioMEMs development.
Implementation Method 1
The substrate can include cell adhesive regions and cell repulsive regions. The cell adhesive regions can be positioned over the sensors.
Data Source
AI summary
The method of culturing cells disclosed herein includes printing cells onto a substrate that includes cell adhesive regions and cell repulsive regions. The cells are suspended in a printing medium to create a cell suspension, and a volume of the cell suspension is loaded into a printer. A cell adhesive region of the substrate is aligned beneath the printing channel of the printer, and droplets of the cell suspension are dispensed from the printing channel directly onto the cell adhesive region. Contact of the dispensed droplets with cell repulsive regions of the substrate is limited, either by targeting of the droplets to the cell adhesive regions, by repulsions generated by the cell repulsive areas, or both. The cells adhere to the cell adhesive regions to create a cell pattern, and are maintained thereafter in a physiologically suitable environment.


