University of Pittsburgh

Novel Microfluidic Device for High-Throughput Tissue Analysis

University of Pittsburgh researchers have developed a novel, modular microfluidic microwell bioreactor. Designed to hold biological tissue or samples of varying type and size in microwells, connected by microfluidic channels that can add different media to samples, these bioreactors could be vital research tools. With the possibility to modify the dimensions of these wells and arrange into arrays of various size, these optically transparent wells allow for monitoring of high-throughput samples to improve research.

Novel, modular microfluidic wells have been developed. These wells can have multiple inlets and outlets for perfusion or diffusion of media into wells to monitor real time reactions using optical monitoring. These microwells can be used as single wells or an array such as a 96-well plate. 

Description

High-throughput optical monitoring is a commonly used research technique in drug screening and monitoring cell morphology in response to stimuli (e.g., stress), typically using 96-well plates. The dimensions of these novel microwells can be adjusted during fabrication and customized to the samples being analyzed and to the unique experimental needs. These wells can be used as either a single well, or arranged into larger arrays, with lids and bases easily assembled using clip-in connections and screws to allow for use in high-throughput analysis. Together with the inclusion of microfluidic channels to deliver media to samples, these wells can act as bioreactors requiring only a small amount of tissue sample and could expand the application of high-throughput optical monitoring in research.

Applications

- Cell development research
- Stress response research
- Treatment response research

Advantages

Commercially available 96-well plates used in high-throughput screening typically require sample volumes between 40–280 µL. This requirement can limit the use of high-throughput optical monitoring in experiments when only smaller volumes (e.g., cells transfected with expensive reporter genes) are available, or when larger sample volumes are required (e.g., multiple 3D constructs including polymeric scaffolds and hydrogels).

This novel microfluidic device overcomes these limitations. The device consists of microwells, fabricated to different dimensions suited to the sample size, potentially as low as 1µL and large enough for polymeric structures. Additionally, microwells can be arranged into arrays, like 96-well plates, allowing for multiple sample analyses using high-throughput techniques. The bioreactor can also include multiple inlets and outlets to transport fluids to microwells using either diffusion, perfusion, or combined methods, enhancing the application of these bioreactors in in vitro research.

Invention Readiness

Prototype devices have been produced with a microwell volume of 10 µL. Each microwell can be sealed with a removable base and lid, equipped with O-rings. A small circular glass cover slip placed between each microwell and the lid, allows clear optical access to the microwell. In the prototype, components are held together by screws for ease of re-use, but future designs could include clip-in connections for rapid assembly.

IP Status

https://patents.google.com/patent/US20160201037A1/en