Implantable Microdevice for Multiplex Drug Screening
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Solution Overview
Problem
Current methods for testing cancer therapies lack the ability to maintain tissue original complexity with an intact immune system, limiting the development of precision medicine tools that can efficiently assess multiple drugs simultaneously and predict durable treatment responses.
Innovation Solution
A novel pre-clinical model system using implantable microdevices with microwell reservoirs for localized intratumoral drug delivery and multiplex immunohistochemistry analysis to assess tumor cell responses, incorporating biomarkers like Galectin-3 and Neuropilin-1 to predict treatment efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If ex vivo tissue samples are used for drug testing, then tissue original complexity and intact immune system are maintained, but the ability to efficiently assess multiple drugs simultaneously is limited
Solution Approach 1:
The system divides the drug delivery function into multiple independent microwell reservoirs (at least 8 reservoirs) within a single implantable device. Each reservoir can hold different anticancer agents, allowing simultaneous testing of multiple drugs in different regions of the same tissue sample without requiring multiple separate devices or complex external delivery systems.
Solution Approach 2:
The implantable microdevice serves multiple functions: it acts as both the drug delivery system and the structural framework for organizing multiple test conditions within a single device. The device can deliver multiple drugs, maintain tissue viability, and enable spatially-resolved analysis all through a single integrated platform.
2Productivity
If implantable microdevices with multiple reservoirs are used, then multiple drugs can be tested simultaneously, but device complexity increases
Solution Approach 1:
The device is segmented into multiple independent microwell reservoirs that can be individually loaded with different drugs. This segmentation allows parallel testing of multiple anticancer agents simultaneously in different regions of the tissue sample, dramatically increasing assessment throughput compared to sequential testing methods.
Solution Approach 2:
The microwell reservoirs are arranged in arrays with each reservoir serving as a replicate testing unit. This copying approach allows the same basic reservoir structure to be repeated multiple times, enabling high-throughput screening while using a standardized, manufacturable design for each individual reservoir unit.
3Manufacturing precision
If localized intratumoral drug delivery is implemented, then spatial resolution of drug effects is improved, but manufacturing precision requirements increase
Solution Approach 1:
The delivery system is segmented into discrete microwell reservoirs that are pre-formed during manufacturing. Each reservoir acts as a predefined delivery zone with controlled dimensions and positioning, ensuring consistent spatial resolution of drug effects without requiring complex post-manufacturing assembly or calibration procedures.
Solution Approach 2:
The microwell reservoirs are designed with specific geometric parameters (volume, depth, opening size) that control drug release characteristics and spatial distribution. By optimizing these parameters during manufacturing, the system achieves high spatial resolution for detecting drug effects while using standard fabrication techniques.
Data Source
AI summary
Provided is an ex vivo system allowing for assessment of tumor and other cell responses to pluralities of agents or agent combinations using a microdose delivery microdevice implanted into an ex vivo tissue sample. The microdevice permits localized intra-tissue sample agent delivery and provides the ability to predict the drug efficacy within days after application. Systems for maintaining tissue samples ex vivo over hours to weeks are provided, which can be used to house tissue samples during exposure of the tissue to microdoses of agents applied using the delivery microdevices. Also provided are biomarkers (galectin and/or neuropilin) useful in evaluating the efficacy of agents.