Biomicrofluidics and Photonics Lab

Joe Fujiou Lo, Ph.D.

Associate Professor

Department of Mechanical Engineering

Bioengineering Program

College of Engineering and Computer Science

University of Michigan-Dearborn

Research Focus

Innovate Microengineering to Transform Biomedical and Biophotonics Research

The theme of DBP lab's research centers on the application of novel technology and untapped physical phenomena to address critical biomedical needs, culminating in truly multidisciplinary engineering solutions. In turn, our work advances the understandings of wound healing and diabetes diseases.

I. Biomedical Devices

Oxygen Microfluidics: Our work in this area explores gas-based microfluidics, in contrast to conventional liquid microfluidics. There has been an unmet need in modulating oxygen concentrations for biological experiments involving cells and tissues. Our initial work began by applying hypoxia to cells and pancreatic islet for diabetes studies. We have demonstrated techniques for training islets for hypoxia, as well as a novel device to test an array of islets for transplant applications, in collaboration with the University of Illinois at Chicago. Additionally, We have applied oxygen microfluidics to improve neuroscience experiments and “smart bandages” for wound healing applications. Moreover, We’ve pushed the boundaries of oxygen microfluidics by demonstrating arbitrary and circular shaped gradients for wound healing.

Circular hypoxia modeling wound healing.

Smart Microgel Biosensors: Keeping with the theme of leveraging novel engineering, we applied optimal microfluidic manipulation of porous hydrogels for sensing biomolecules. Suspension assay, based on beads and hydrogel droplets, has been an active area of research. However, there is a mismatch between the microscaled beads/droplets versus the bulk fluid in which they are suspended. Boundary layer next to their surfaces prevents convective mass transport and reagent turnover, limiting reaction rates for biosensing. We addressed this issue by developing microfluidic arrays to handle porous hydrogel droplets, whose microchannel flow enhances reaction kinetics. Using this technique, a sensitive pg/mL vascular endothelial growth factor (VEGF, a cancer and disease marker) detection assay was achieved. Furthermore, sensitive detections can benefit diabetes screenings, and a multiplexed detection panel was further developed for three diabetes antibodies for clinical screening. The microfluidic biosensor technique we’ve developed can also enable novel biological experiments, where the assay itself can modify the target cell of interest and report the outcome in a single device.

Porosity tuned hydrogel for diabetes autoantibodies detections.

3D Printed MicroTesla Fluidics: Nichola Tesla patented the Tesla turbine for geothermal power generation in 1910. However, the boundary layer flow characteristics of its multi-disk rotor makes it well-suited to produce non-pulsatile microfluidic flow. There was a lack of an integrated, precise, non-pulsatile flow source for microfluidics, rendering tiny devices to be chained to a whole desk-full of pumps and accessories. Thus, we leveraged lithography-based 3D printing to miniaturize the Tesla pump (µTesla), allowing the creation of high resolution, smooth disks in microscales. The original concept of the µTesla pump was optimized for microfluidic flow. On-going work for µTesla version two (smaller than a penny) is looking at the transient responses of the pump to characterize its performance under different rotor noise conditions, important criteria for stable flows and modeling diffusion during long term (24 hours) biological experiments. The goal for these µTesla research is to create a novel integrated bioreactor for cell culture based assays, transforming microfluidic devices into real, practical solutions for clinical research.

Porosity tuned hydrogel for diabetes autoantibodies detections.

II. Biophotonics

Frequency Domain Fluorescence Lifetime Tissue Discrimination: Our work in this area arose from my experiences in applying oxygen “smart bandages” to wound healing, where the need for destructive tissue histology conflicts with the goal of healing itself. Collagen fibers, as a major structural component in tissue, undergo changes during healing that can only be investigated by histology. To address this issue, we have developed a biophotonic, non-invasive technique to quantity the types of collagen in tissue without any contact. We incorporated the concept of signal modulation of Linear Time Invariant (LTI) systems from engineering to extract photonic “response functions” from tissue, enabling the identification of different types of collagen just by shining light. This frequency domain (FD) fluorescence lifetime method can be applied to monitor wound healing, tumor fibrosis, and skin scaring, among other tissue applications.

Fluorescence Lifetime Tissue Histology: To extend the FD tissue discrimination technique, we’ve developed a compact LED based imaging microscopy system to replace imaging histology. This expanded our tissue discrimination technique to other extra-cellular-matrix (ECM) proteins and disease modified components such as glycated biomolecules. The cost-effective ($17k) system we developed utilized novel 100 MHz modulated LED light sources and infinity-corrected microscopy optics to create an integrated, low-complexity system that competes with bulky Fluorescence Lifetime Imaging Microscopy (FLIM) systems costing half of a million dollars. Furthermore, we are developing a biophotonic tissue model based on ECM and diseased biomolecules in order to quantify the changes during wound healing. Such quantitative model was previously suggested but unavailable, and its establishment means that a standardized “Biophotonic Collagen Biopsy” can be created to accelerate numerous tissue-based biomedical studies.