New Inventions

Monomeric Fluorescent Protein-Ligand Complexes with Strong Fluorescence in the Far-Red Region

Research from the University of Wisconsin-Washington County in collaboration with the Institute for Stem Cell Biology and Regenerative Medicine in India, has resulted in the development of monomeric variants of the naturally occurring Sandercyanin Fluorescent Protein (SFP) using site-directed mutagenesis. This work has stemmed from earlier research focused on development of the tetrameric form of SFP, a biliverdin-binding lipocalin protein originally isolated from the mucus of the blue walleye fish, Sander vitreus. Monomeric variants of SFP (mSFPs) have been found to possess the same non-covalent, bili-binding characteristics of the tetramer but are one-quarter the size (~18.6kDa) and do not oligomerize. They are therefore anticipated to be more useful in a host of biotechnology applications. Like the tetrameric form, the mSFPs have a large stokes shift (375nm/675nm) and fluoresce in the far-red or near infrared region, which is advantageous for a wide range of applications including investigation of protein-protein interactions, spatial and temporal gene expression, assessing cell biology distribution and mobility, studying protein activity and protein interactions in vivo, as well as cancer research, immunology, and stem cell research and sub-cellular localization. In addition, the newly developed mSFP’s far-red fluorescence is particularly advantageous for in vivo, deep-tissue imaging.
(Dec 20, 2016) T150029WO01

Retinoic Acid: A New Treatment for Sleep Apnea and Hypopnea

UW–Madison researchers have developed a new method for treating sleep apnea and hypopnea with retinoic acid.

A patient can be given a retinoid or retinoic acid receptor agonist such as all-trans RA (ATRA), 13-cis RA (isotretinoin) or 9-cis RA (alitretinoin). These compounds target the mechanisms that cause sleep apnea in two ways. First, they increase the respiratory drive (urge to breathe). Additionally, they reduce the apneic threshold (the level of CO2 necessary for the induction of breath) to normal levels.
(Oct 13, 2016) P150330US02

Improved System for Stroke Therapy and Rehabilitation

UW-Madison researchers have developed an improved system for stroke therapy and rehabilitation.  This system collects movement intention signals from the brain in real-time via EEG and initiates functional electrical stimulation (FES) of the appropriate muscle(s) to assist the neurons in regrowing their connections from the brain to the muscles along the correct pathways.  Additional general sensory stimulation may be added to this therapy to further encourage proper neuron regrowth. 
(Oct 10, 2016) P09245US02

Temperature Gradient Handling System for Surface Plasmon Resonance (SPR) Measurements

Researchers in the Department of Chemistry and Biochemistry at the University of Wisconsin-La Crosse have developed a surface plasmon resonance (SPR) based method for measuring, in a single experiment, the temperature dependence of binding kinetics for biomolecular interactions. The method is based on a novel sample handling system that generates a spatial temperature gradient across an SPR sensor and is label free.
(Aug 17, 2016) T150042US03

High Accuracy Angle Measuring Device for Industrial, Medical, Scientific or Recreational Use

A UW-Stout researcher has developed a high-accuracy angle measurement system that addresses the problems inherent to commercially available systems. In this novel device, a high accuracy rotary optical encoder is controlled by a microprocessor. The encoder consists of rotating optical disks and sensors that are precisely formed and placed to read angles with 0.001 arc second sensitivity (average) and better than ±0.1 arc second accuracy (single readings), which is comparable to the accuracy of the high-end commercial encoders currently on the market. This accuracy is maintained with strategies that combat the mechanical sources of error that are known disadvantages of other devices. The system can also be adjusted to compensate for any asymmetrical shifts that may occur. Mechanical sources of error and noise are further minimized by precision placement of disks and sensors, as well as low-friction reference points that keep components centered and level during rotation. In addition, multiple sensor heads eliminate major readout errors and remove the need for recalibration. All of these features and benefits are contained within a design that is both compact and portable. Beyond high accuracy and portability, the cost of this new angle measurement system is substantially lower than a high-end commercial system because it is easily constructed from readily available industrial grade components, bringing the production cost to roughly $2,000. Strikingly, this cost is comparable to the advertised price of other rotary position encoders that are less than one tenth as accurate. Its high accuracy, low cost, and portability make this new angle measurement system a strong option for use in virtually any of the current applications for absolute rotary encoders.
(Aug 8, 2016) T130018US02

“Green” Catalytic Systems for Solvent-Free Alcohol Oxidations

Research from the University of Wisconsin-La Crosse has led to the discovery and development of a novel suite of catalytic systems for industrially-relevant green oxidations including the oxidative conversion of primary and secondary alcohols to value-added aldehydes and ketones. Similar systems have been developed for the oxidation of olefins to produce important epoxides, and for the oxidation of alkanes to produce alcohols. Specifically the team has developed a series of iron-based catalysts known as ‘helmet’ phthalocyaninaoto complexes of iron(III). Preliminary studies have focused on the use of what is commonly referred to as the ‘diiPc’ iron(III) system. Notably, the team has shown that this system is capable of catalytically oxidizing a diverse array of substrates including five non-benzylic alcohols (1-pentanol, 2-pentanol and cyclohexanol as well as 2,4-dimethyl-3-pentanol and 5-hydroxymethylfurfural) in the absence of added organic solvent. The presence of water as the monodentate axial ligand in the diiPc complex allows for markedly increased solubility in non-aromatic alcohols, making it an ideal catalyst for use with a much wider and more diverse range of substrates under solvent free conditions. It is envisaged that modification of the diiPc and related ligands will be undertaken to impart further enhancements to catalyst solubility in substrates or water, and/or superior stability in substrate alcohols. In addition to the diiPc system, the team have also developed a means of forming derivatized catalysts utilizing what is commonly referred to as a “helmet naphthalocyaninato” iron(III) complex. Specifically, a sulfonated version has been produced that possesses excellent solubility in water due to the added hydrophilic groups. To date, the sulfonated helmet naphthalocyaninato complex has been shown to provide for efficient formation of acetone from isopropanol as well as conversion of 2-pentanol to 2-pentanone using hydrogen peroxide as the primary oxidant. As such we anticipate that the same system would also be effective in the oxidation of 2-butanol to produce methyl ethyl ketone (MEK), an important commodity scale industrial chemical, and in many other commercially important transformations. Furthermore, preliminary studies have shown this molecule can be immobilized on various solid supports including anion-exchange resins, thereby resulting in a heterogeneous catalyst that can be utilized in the development of catalytic transformations that occur under flow conditions. Additionally, we now know that the sulfonated catalyst efficiently catalyzes the oxidation of phenol with hydrogen peroxide to produce para-benzoquinone. This transformation, along with other related reactions, is very important in the treatment of wastewater.
(Jul 22, 2016) T150040US03

Nylon-3 Polymers Active Against Clostridium Difficile

UW–Madison researchers and collaborators at Emory Medical School have developed nylon-3 polymers and copolymers active against C. difficile. The polymers have been shown to inhibit outgrowth/growth of the bacteria in spore and vegetative form.
(Jun 30, 2016) P150214US02

New Synthetic Ligands Target RhlR Quorum Sensing Receptor

UW–Madison researchers have identified novel synthetic molecules, including agonists and antagonists, capable of modulating quorum sensing in Gram-negative bacteria. Several exhibit higher potency than the native ligand.
(Apr 29, 2016) P160350US01

DNA “Millichip” Enables Low-Cost, High Throughput Gene Expression Analysis

UW-Madison researchers have developed a DNA “millichip” designed for low-cost, high throughput gene expression analysis in whole genomes.  The millichips consist of 1,000 to 100,000 different oligonucleotides probes immobilized on small solid support arrays with relatively high density.  The probes, which range from 30 to 100 nucleotides long, occupy separate, known sites in the arrays. 

For example, a maskless array synthesizer (MAS) can be used to synthesize about 800,000 70-mer oligonucleotides on a glass microscope slide.  Then the slide is divided into 96 pieces, each containing about 30,000 of the 70-mer DNA sequences.  These small pieces can be used in any experiment that uses standard DNA chips.

Because the millichips are small, less than 10 cubic centimeters, small volumes of solutions can be used for analysis.  In addition, the small substrate size allows the arrays to be visualized using instrumentation readily available in research laboratories.
(Apr 4, 2016) P07308US02