Microfluidic Co-Culture SELEX for High-Specificity Aptamer Selection
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Solution Overview
Problem
Conventional SELEX techniques for developing aptamers suffer from insufficient specificity, especially when applied to personalized cancer therapy, as they fail to adequately discriminate between cancerous and non-cancerous cells, and in vivo animal models distort target affinities.
Innovation Solution
A microfluidic device platform is used to model individual systemic models of patients by co-culturing cancerous and non-cancerous cells, allowing for the selection of aptamers with greater specificity through a method that includes modular device arrangements, controlled fluid circulation, and the SELEX technique, mimicking physiological conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional SELEX techniques are used for aptamer selection, then the process is simple and fast, but the specificity for discriminating between cancerous and non-cancerous cells is insufficient
Solution Approach 1:
The selection system is divided into multiple independent microfluidic chambers, each containing different cell populations (cancerous and non-cancerous cells). This segmentation allows parallel selection processes to occur simultaneously, improving specificity while managing complexity through modular design
Solution Approach 2:
A microfluidic device serves as an intermediary platform that facilitates controlled interaction between the combinatorial library and different cell populations. The device enables precise delivery, exposure, and capture steps while maintaining isolation between different selection environments, thereby enhancing specificity without proportionally increasing operational complexity
2Measurement precision
If in vivo animal models are used for SELEX, then specificity is improved, but the target affinities are distorted by the xeno-animal model
Solution Approach 1:
The invention creates an in vitro copy of the in vivo selection environment using patient-derived cancerous and non-cancerous cells cultured in microfluidic chambers. This copying approach maintains the physiological relevance of human cells while avoiding the distorting effects of xeno-animal models, thereby preserving target affinity accuracy without sacrificing model versatility
Solution Approach 2:
The system changes the selection environment from xeno-animal organisms to human cell cultures in controlled microfluidic conditions. By adjusting parameters such as cell source (patient-derived), culture conditions, and microfluidic flow rates, the system achieves accurate target affinity measurement while maintaining broad applicability to different cancer types and patients
3Measurement precision
If negative selection steps are introduced in SELEX, then non-target binding is reduced, but the degree of specificity remains insufficient to discriminate cell populations in practice
Solution Approach 1:
The invention merges positive selection (enrichment of target-binding species) and negative selection (removal of non-target binding species) into a unified microfluidic platform. Multiple cell populations are simultaneously presented in different chambers, allowing the combinatorial library to undergo both selection pressures in parallel, thereby achieving superior discrimination without proportionally increasing process complexity
Solution Approach 2:
The system transitions from sequential selection steps to a multi-dimensional parallel selection approach. By organizing different cell populations in spatially separated but functionally integrated microfluidic chambers, the system adds a spatial dimension to the selection process, enabling simultaneous positive and negative selection that dramatically improves cell population discrimination
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 enhances aptamer specificity for personalized cancer therapy by improving discrimination between cell populations and reducing the need for animal experimentation, enabling more precise targeting and predicting therapeutic efficacy.
Implementation Method 1
circulate the fluid in the system for an adequate period
Implementation Method 2
the affinity of a combinatorial library of nucleic acids is enriched by SELEX from consecutive steps of exposure, capture and amplification of the species most capable of binding to the target of interest
Data Source
AI summary
This invention consists of a method for the development of personalized target anticancer therapies based on aptamers and through the systemic modeling of an individual in microfluidic devices. This invention is embodied in microfluidic devices, connections, systems, and methods for the development specific aptamers for the relevant complex biological environment targets. In a first mode, the invention provides methods for the development of target therapies which involves the maintenance of target cancerous cells in co-culture with non-target and non-cancerous cells by using microfluidic devices modularly arranged in closed systems for the development of aptamers. In a second mode, the invention provides a method for the development of target therapies, which includes the maintenance of target cells in co-culture with non-target cells by using microfluidic devices modularly arranged in closed systems. In this case, the invention provides the development of aptamers for the relevant target in homeostatic balance with the components of the fluid conditioned by the co-culture with non-target cells.