Arterial Coupler

Several different surgeries require the end-to-end anastomosis of blood vasculature. On larger blood vessels this can be accomplished by hand-suturing the two ends together. However, as the blood vessels shrink in size hand-suturing becomes more difficult. Current techniques involve intraoperative microscopes and ultra-thin needles. These techniques require specialized training and present serious potential complications. Our goal is to develop a mechanical device that would simplify the anastomosis of arteries 1 to 5mm in diameter and provide an alternative to hand-suturing. Several device design iterations have already been documented, and we are currently optimizing the design for effectiveness and ease of use.

Mechanical Leech

The Mechanical Leech (open image here) is a medical replacement for biological leeches, providing the necessary venous congestion relief that is needed for leech therapy.  Live leeches are currently used during post-surgical skin graft procedures to remove pooling blood at the surgical sites.

Leech therapy is the practice of introducing leeches onto reattached tissue post-surgery to relieve venous congestion in the region.  The primary function of the leech is to prevent the pooling of blood and reduce pressure in areas where arterial blood flow is adequate to supply blood but the venous blood flow is insufficient to remove it. This gives the body time to form new veins to handle the return blood flow. The leeching process accomplished naturally through the feeding process of leeches that create a small incision, secrete an anticoagulant, and remove the excess fluid.

In addition to eliminating a patient’s repulsion of biological leeches, the Mechanical Leech will provide more consistent, controllable performance over its parasitic counterpart, making it more desirable to doctors and surgeons to use during therapy.

Microfluidic Semen Preparation

Through this NSF-funded project, we work to create a device capable of performing the semen prep procedure required for intrauterine insemination (IUI). The technology is required to remove WBCs from the sample, and wash the cells from the seminal plasma. The project is done in collaboration with the Andrology Clinic at the University of Utah and with the Salt Lake-based startup company NanoNC.

Microneedles

Nerve Regeneration

Sperm Isolation from mTESE Samples

We are currently working to create a device capable of isolating sperm cells from microTESE samples. MicroTESE samples are testicular biopsy samples taken when no sperm are found in the ejaculate. The samples contain millions of cells, very few of which are the desired sperm cells. The current clinical practice of manually searching for the sperm cells could be greatly accelerated with a microfluidic hardware system capable of isolating the sperm cells from other contaminating cells and debris. The project is done in collaboration with the Andrology Clinic at the University of Utah and with the Salt Lake-based startup company NanoNC.

Exosomes

Exosomes are the smallest of the membrane bound vesicles that cells are known to shed. They are 30-100nm in diameter and partially overlap with microvesicles which are 100nm to 1000nm in size. Both groups of particles are biologically important. However their small size-especially for exosomes- makes them difficult to study with traditional light microscopes unless many are localized in a single area.

While not every study distinguishes between these two classes of microvesicles, some of their cell signaling features do suggest a direct role in cancer metastasis. For example, they contain growth
factors, mRNA, and miRNA; They have been shown to transfer onco-receptors to normal cells, promote angiogenesis, direct cancer growth, and make cancer worse. They also can be used to remove toxins from cells, and may serve as biomarkers themselves for disease states.

Current techniques for separation and isolation of exosomes remains time Consuming. These methods typically rely on overnight centrifugation, or on expensive affinity-capture techniques that can only target known proteins. Because there is a need for a reliable method to supply large volumes of
exosomes for further study, the Gale group is developing methods and devices based on Field Flow Fractionation to address these and other technical aspects of exosome harvesting and isolation.

The goal of this research is to develop a device capable of continuously harvesting exosomes from a biological sample.

Micro Field Flow Fractionation

Field flow fractionation (FFF) is a family of techniques used for the separation of nanoparticles, proteins, DNA, viruses, and other materials based on size, charge, or other physical properties.  We have primarily explored how miniaturization effects these systems.  We have explored microscale electrical and thermal systems, as well as the SPLITT versions.  We are also developing techniques using cyclical fields for these systems.  Specific projects included in this area:

  • Microscale Electrical FFF
  • Microscale Thermal FFF
  • Microscale Thermal Electrical FFF
  • Cyclical Electrical FFF
  • Microscale Electrical SPLITT
  • Reduction of End Effects in FFF

Note that the Center is organizing the 13th International Symposium on Field- and Flow- based Separations.

Exosomes are the smallest of the membrane bound vesicles that cells are known to shed. They are 30-100nm in diameter and partially overlap with microvesicles which are 100nm to 1000nm in size. Both groups of particles are biologically important. However their small size-especially for exosomes- makes them difficult to study with traditional light microscopes unless many are localized in a single area.

While not every study distinguishes between these two classes of microvesicles, some of their cell signaling features do suggest a direct role in cancer metastasis. For example, they contain growth
factors, mRNA, and miRNA; They have been shown to transfer onco-receptors to normal cells, promote angiogenesis, direct cancer growth, and make cancer worse. They also can be used to remove toxins from cells, and may serve as biomarkers themselves for disease states.

Current techniques for separation and isolation of exosomes remains time Consuming. These methods typically rely on overnight centrifugation, or on expensive affinity-capture techniques that can only target known proteins. Because there is a need for a reliable method to supply large volumes of exosomes for further study, the Gale group is developing methods and devices based on Field Flow Fractionation to address these and other technical aspects of exosome harvesting and isolation.

The goal of this research is to develop a device capable of continuously harvesting exosomes from a biological sample.

The Center has several projects related to using microfluidics for delivery of biopolymers, the physics of microflows, and ways to minimize unwanted microfluidic (or macroscopic) effects. For example, we have recently developed a promising technique for the manufacture of microneedles.

Detectors

To complement the Center’s separation capabilities, the lab has developed several microscale particle detectors that can be integrated into microfluidic systems. These detectors rely on either electrical impedance or optics for detection.

  • DC Conductivity Detector
  • AC Conductivity Detector
  • Impedance Spectroscopy Detector
  • Optical absorbance detection
  • Evanescent optical detection

Continuous Flow PCR

We work on the optimization of a microfluidic device for continuous flow polymerase chain reaction (PCR). PCR is the process by which copies of DNA are produced for analysis in a variety of lab applications including testing for disease, analyzing cancer, and other biological studies. PCR protocols currently take about one hour, however much faster systems have recently been theorized and developed. Our work aims to provide a device ready for commercialization that could perform PCR in less than five minutes. This type of device will not only reflect significant time savings, but will also be a significant contribution to point-of-care diagnosis and many other medical products. The project is done in collaboration with the Wittwer Lab and Andrology Clinic at the University of Utah.

Sperm Separations

  • Understanding the Bio-particle Behavior in Spiral Channels: The ultimate goal of this project is to unravel the physics of cell/sperm sorting in a device with spiral channels and understand how some bio-particles order themselves in the device. Sperm separation is a fundamental process for in-vitro fertilization (IVF) using sperm from testicular biopsies. For sperm preparation to start, we need to segregate sperm from unwanted particles (RBC, WBC, etc.) using inertial focusing technique. The mechanism by which sperm focuses is not known completely. Sperm cells show remarkably different focusing behavior compared to other cells (Ellipsoid, Cylinder, Red Blood cell, etc.). This phenomenon has fascinated our interests as researchers, raising questions like: How and why do various particle shapes find their equilibrium position and where does this difference come from? We have chosen spiral channels over other designs because of the property of curved channels to create an additional secondary flow effect known as Dean vortices. The dean vortices accelerate and modify particles’ inertial migration process for better cells focusing. By carrying out particle simulations that mimics the behavior of a living cell in the device coupled with experimental analysis, we (Brady Goenner and I) aim to elucidate physics principles governing sperm focusing to understand asymmetrical particle focusing behavior in the spiral channel.
    Particle sorting in a Straight Channel vs Spiral Channel [Sorting algal cells by morphology in spiral microchannels using inertial microfluidics, Allison Schaap, et al (2016)]
  • Automated Device for Sperm Purification: NSF funded microfluidics project. The work involves building and developing rapid, highly automated, and controllable instrumentation which will be capable of isolation and enrichment of Sperm cells from patients with low sperm counts for in-vitro fertilization (IVF). We aim for our system to both increase pregnancy rates of infertile couples and provide separations faster than anything that is currently available on the market. The project is done in collaboration with the Andrology Clinic at the University of Utah and with the Salt Lake-based startup company NanoNC.

Zebra Fish Genotyping

Professor Bruce Gale, his post doc, Raheel Samuel, and Ph.D. student Chris Lambert, in collaboration with the University of Utah’s medical school, have developed a microfluidic system that enables high throughput, non-destructive genotyping of live zebrafish embryos by making it possible to collect DNA samples from these tiny animals at an early stage. It may come as a surprise, but the common aquarium zebrafish (Danio rerio) is extensively used by biomedical researchers as a model organism for determination of genetic and biochemical pathways, identification of basic biological activity, and drug discovery. Their DNA collection system works by gently extracting genetic material from live zebrafish embryos (less than one mm in size) before they are 72 hours old. The genetic material from the embryo can then be characterized using a variety of DNA analysis tools. This system enables a single user to perform 96 DNA extractions from individual embryos without harming the embryo and within 30 minutes. That’s 95 percent faster than current methods. The technology has recently been licensed to a spinout company from the University of Utah, wFluidx, that is already finding great success in selling the systems.