New Microfluidic System Advances Barrier Tissue Research

At a Glance

Researchers at Colorado State University have developed a groundbreaking system to study live tissue health and function in real time. This innovative technology maintains tissue viability for extended durations while providing continuous data on tissue integrity. The system combines microfluidic design with integrated sensors, offering a more accurate and dynamic model of tissue systems. It enables researchers to investigate tissue responses to various conditions, advancing studies in drug development and disease research.

Background

Understanding the health and function of tissue systems is essential for advancing research on diseases and developing new therapies. Many traditional methods struggle to replicate the natural complexity and environment of live tissues, limiting their accuracy and applicability. Tools that preserve tissue viability and provide real-time functional measurements are crucial for creating better physiological models and reducing reliance on animal testing. This technology bridges that gap, offering a comprehensive solution for studying tissue health and responses to stimuli, and is built on the foundation of CSU Tech 2019-084.

Overview

The CSU-developed microfluidic system is designed to preserve the viability and integrity of live tissue samples for up to 72 hours. It achieves this through an innovative chamber that mimics in vivo conditions using dynamic media flow, oxygen gradients, and nutrients that support the tissue’s microbiome and cellular health. Integrated electrodes within the system measure transepithelial electrical resistance (TEER), providing continuous, real-time feedback on tissue barrier integrity without disrupting the experiment.

Compared to traditional tools like Ussing chambers or organ-on-a-chip devices, this system combines long-term tissue viability with real-time monitoring, enabling more accurate and detailed studies. It supports multiple samples from the same tissue donor simultaneously, reducing variability and improving throughput. After 72 hours, tissue samples retain key biological features such as tight junctions and mucus layers, demonstrating its effectiveness as a physiological model.

Figure 1. Major components of the microphysiological system. Including the microfluidic chamber (a–f) and the system-level housing (g–h). a. Expanded view of a full chamber, with all components labeled. b. Closed chamber with a closeup view of the tissue and PDMS clamped between two chamber halves. c. Tissue explant before and after the experiment. d., e. The actual manufactured chamber assembled (front and back, respectively). f Flow simulation through the chamber’s microfluidics. g. Expanded view of the microphysiological system. h. The manufactured and fully assembled system with three chambers connected the system.

Figure 2. Tissue health was maintained over 72 hours in the device and monitored after media treatment. a. Control tissue after 72 h experiment. (i) Tol blue staining showing maintenance of colon morphology, MUC = mucus layer, m = mucosa, cr = crypt, sm = submucosa, me = muscularis externa. (ii) Claudin-1 immunoreactivity in vivo. (iii) Claudin-1 immunoreactivity in 72 h ex vivo shows maintenance of tight junctions between epithelial cells and crypts. (iv) UEA-1+ material in vivo. (v) UEA-1+ material ex vivo confirming maintenance of epithelial cells and mucus layer. (vi) Quantification of goblet cell number per apical crypt in in vivo vs. ex vivo tissue, n = 3, error bars show the standard error. b. Collagenase treated, and acidic luminal media resulted in alterations in goblet cell morphology and tight junction expression indicative of increased barrier permeability. (i) Goblet cells labeled with UEA-1 become circular after collagenase treatment. (ii) Acidic media resulted in loss of goblet cell shape and sloughing off of cells near the lumen. (iii) Alterations in tight junction protein expression (claudin-1) following collagenase treatment. (iv) Claudin-1 expression decreased considerably with exposure to acidic media indicative of substantial barrier disruption. (v) The bar graph shows a distinct reduction in transepithelial electrical resistance (TEER) after exposure to different media composition. The difference in TEER was measured from 24 to 48 h mark after the tissue was enclosed in the device, with the media change occurring at 24 h. The three media compositions consist of a control media, collagenase treated media, and low pH media (more details about media composition in “Animals, Tissue Collection, and Media Preparation”). L = lumen, TEER values are normalized to the membrane surface area of the chamber, 0.0314 cm2. Control: n = 4, Collagenase: n = 10, Low pH: n = 3, error bars show standard error, **p < 0.005; ***p < 0.0001.

Benefits

Maintains tissue viability for up to 72 hours, outperforming traditional systems.
Enables real-time TEER measurements for continuous barrier integrity data.
Mimics natural conditions with dynamic media flow and oxygen gradients.
Supports multiple simultaneous experiments from the same donor tissue.
Compact, reusable design compatible with standard laboratory setups.

Applications

Drug discovery and testing.
Research on diseases involving barrier dysfunction, such as inflammatory bowel disease or neurodegenerative disorders.
Academic and industrial research on tissue barrier mechanisms.

Publications

Way, et al (2024) “A microphysiological system for studying barrier health of live tissues in real time.” Nature. https://doi.org/10.21203/rs.3.rs-4078220/v1

Last Updated: March 2025

Opportunity

Available for Exclusive Licensing
TRL: 4

IP Status

US Provisional Patent

Inventors

Thomas Chen
Ryan Way

Reference Number

2024-049

Licensing Manager

Jessy McGowan
Jessy.McGowan@colostate.edu
970-491-7100