This portfolio of microfluidic technologies improves cell culture techniques. Current cell culture techniques have several limitations: they are resource and process intensive, the culture environment is inconsistent, and manual manipulation is both time consuming and error prone.
These microfluidic inventions enable more consistent cell culture environments; allow use of high throughput devices which provide speed and consistency; conserve cell-cell factors to maintain cell-cell communication; and ultimately reduce operator error.
High Throughput In Vitro Fertilization (IVF) Device compatible with Multi-Head Flow Cytometry Systems
This invention consists of microchannels to incubate oocytes and embryos. Microchannels are aligned to match the multi-head pipettor of a fluid handling robot with the dispenser of flow cytometers. After a certain amount of incubation time, depending on species, sorted sperm are introduced into the microchannels using a flow cytometer. The microchannels direct the movement and location of the sperm toward the oocyte. Once fertilized, embryos are removed from the fluid handling root and are ready for downstream steps. This process is very low shear, can be easily scaled for high throughput and should improve the yield of current processes.
High Throughput Migration Device for Chemotaxis Studies
Most chemotaxis devices cannot be used in high throughput studies. The geometry and surface tension properties of this invention use fluidic resistance to provide convection and a flow barrier, which then enable the development of concentration gradients. Fluidic resistance ensures this gradient is not disturbed, preserving cell-cell factors. The chamber has a cell inlet, a chemoattractant is introduced in the source channel, and a blank medium is introduced in the sink channel.
Microfluidics Well Insert (MWI) for Oocyte/Embryo Culture
To facilitate culture microenvironments for embryos similar to in-vivo, this invention provides a ready-to-use culture system made using soft lithography technology. This invention has two versions: channel-less and channeled. The channel-less version is composed of wells of a size especially tailored for the characteristic size of the particular species of oocyte/embryo being cultured. This allows for a flexible platform that will accommodate a wide variety of animal species. The channeled version has microchannels networked between the wells of the channel-less version, so that cell-cell communication between oocytes/embryos can be maintained during medium change. This invention is particularly useful for culturing zona pellucida-free oocytes and embryos as the well holds the cells together much as the zona pellicuda would with intact oocytes or embryos. This invention is easily scalable and fits into standard culture dishes.
Automatic Top-Off System using a Surface Tension-Based Valve
This liquid handling system automatically fills culture wells to desired levels without operator handling. Liquid is passively added as surface tension drops, maintaining the medium at a constant level without manual manipulation. This has the following benefits:
Scalable to high-throughput
Culture environment not disrupted
Risk of operator error reduced
Open-Close-Open-Close-Open (OCOCO) Microchannel System
Microchannels provide good micro-environments for cell/embryo/oocyte culture and chemical analysis. However microchannels are very inconvenient for loading or accessing samples. This invention uses passive pumping to change mediums or reagents. This invention does not use any connecting channels or tubing, thus eliminating waste. It can be easily expanded for high-throuhput. The figure shows the liquid flowing from small drop to large drop by surface energy forces.
Dr. Yi Lu from the University of Illinois has designed a single protein to tune its electron-transfer ability across a 2-V range of physiological redox potentials. The design of azurin covers a range from +970 mV to -954 mV vs. standard hydrogen electrode (SHE), by mutating only five residues and using two metal ions. Given the wide range of potentials attainable from a single protein possessing the same overall fold and surface properties, these azurin variants enable scientists and engineers to take advantage of these water-soluble redox agents for biochemical and biotechnological applications, such as solar energy transfer and other alternative energy conversions. Since tuning the potentials of many inorganic, bioinorganic and organometallic catalysts can result in catalysts with different oxidation states with dramatically different catalytic efficiency for different substrates, this technology allows tuning of redox properties of numerous catalysts for even wider applications, such as small molecule activation and synthesis of important intermediates or products for pharmaceutical applications.
Ability to tune entire range of redox potentials
Tuned azurins can be used as water-soluble redox agents
Researchers from the University of Illinois have developed a new way to use surface plasmon resonance that allows for quantitative analysis using colorimetric techniques. The invention does not need any instrumentation other than a camera and can be integrated with a smartphone.
This research has received national attention, including coverage in Smithsonian Magazine and Wired.
Dr. Andrew Smith from the University of Illinois has developed new quantum dots with a multidentate polymer coating that minimizes size while maintaining stability and improving efficiency of conjugation. Quantum dots are promising agents for cellular and molecular imaging, but their bulky organic coatings have limited their use in cells. Dr. Smith's quantum dots are small, stable, and can be conjugated to targeting molecules and purified easily.
Dr. Chan has developed a novel fluorescent probe, NitroxylFluor, for the detection of HNO in living cells. This fluorescent probe is highly selective for HNO, is less toxic for use in living cells, and is capable of outcompeting biologic thiols, resulting in better fluorescent detection than existing probes.
NitroxylFluor: A Thiol-Based Fluorescent Probe for Live-Cell Imaging of Nitroxyl, Journal of the American Chemical Society Volume139 Issue 51- Published December 27, 2017
Dr. Chan from the University of IL has developed a highly selective fluorescent probe for cancer stem cells (CSCs) detection. This cell-permeable fluorescent probe is the first to allow direct detection of aldehyde dehydrogenase 1A1, a SCS biomarker, in cell lines and in vivo with high selectivity, low off-target effect and low background.
Dr. Jefferson Chan from the University of IL has developed CoxFluor™, the first “turn on”, isoform specific, fluorescent probe used to detect and image COX-2 activity in vivo and in vitro. The CoxFluor™ probe improves the quality of COX-2 assessments by providing more accurate and real-time measurements of enzyme activity and can be used as a basic science research tool/imaging probe for biological and pharmaceutical studies.
Basic science research tool/imaging probe for biological and pharmaceutical studies