Technologies

Technologies for Potential Startup Companies

As part of its ongoing mission to move inventions created by University of Wisconsin researchers to the marketplace, WARF is eager to help startup companies succeed and advance UW–Madison technologies for public use and benefit.

Many of WARF’s more than 1,500 available technologies may serve as the basis for a startup company. Below is a sampling of those technologies.

These technologies also are available for license by an existing company. WARF licensing managers and associates are leaders in their field and will work with you to custom tailor an agreement to meet your specific needs.

Technologies

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.
P07308US02

Understanding and Treating Nervous System Dysfunction Using Modified Fly Models

UW–Madison researchers have developed new methods to study such time-dependent neurological mechanisms and to screen for potentially therapeutic small molecules using extended third instar stage (ETI) Drosophila larvae. These flies have been genetically modified to remain in the larval period for up to 30 days but are otherwise normal. Given the longer time window, these ETI larvae can be utilized to identify agents that stimulate nerve regeneration, confer neuroprotection or prevent synaptic degeneration.

For such studies, the ETI larvae are fed test compounds (e.g., from a chemical library) and the functional consequences of the test agent on processes such as neuronal survival, axonal regrowth, and synaptic maintenance are assessed in appropriate assays.
P120334US02

Vaccine for Fungal Infections

UW–Madison researchers have developed a vaccine that could prevent infection by many strains of pathogenic fungi.

The vaccine contains calnexin, a common folding protein found in fungi and other eukaryotes. Administered in an effective amount, the vaccine helps a patient’s immune system recognize and destroy fungus it may encounter.
P130116US02

DNA Sequencing with Piezoelectric Nanopore

UW–Madison researchers have developed a method for adjusting in situ the diameter of a nanopore used in a DNA sequencing device via piezoelectric tuning. The ability to control pore dimensions helps control the speed of the material passing through.

The substrate of the device is made of a piezoelectric material like quartz, which physically strains in response to an electric field. The substrate is positioned between reservoirs of conductive fluid and forms a nanoscale opening for DNA and ions. When an electrical signal is applied by a pair of electrodes on either side, the diameter of the opening changes due to piezoelectric shear strain. This constriction slows the passage of DNA through the pore long enough to identify one nucleotide at a time.
P130036US01

Eardrum Nanomembrane Offers Tinnitus Care

UW–Madison researchers have developed a flexible membrane that attaches to the eardrum and detects vibrations. Alternatively, it can be signaled to excite the eardrum.

The nano-thin membrane is made of piezoelectric material. This type of material generates electricity in response to motion, or the reverse, generating motion in response to electricity.

Given this phenomenon, the membrane can be coupled to an antenna and electrodes to act as a transducer, transforming one form of energy into another. Thus, when sound waves strike the eardrum, the shaken membrane produces electrical energy that may be sent out and detected by a transceiver. Conversely, an ingoing radio frequency signal can be received by the electrodes and passed on as audio stimulation to the membrane, causing it to vibrate.
P120327US01

Portable Carbon Monoxide Source for Therapy and Organ Delivery

UW–Madison researchers have developed a portable carbon monoxide generator for medical use that creates precise, therapeutically relevant, concentrations of medical grade CO out of the surrounding air in real time. The device is inherently safe, as it produces only the amount of CO needed for therapy. The device is incapable of producing enough CO to pose a safety hazard.

The heart of the generator is a reaction chamber holding a small cartridge of purified carbon. The CO is produced by heating the carbon in the presence of air that is fed continuously into the reaction chamber. The carbon can be heated by any controllable energy source, such as an electrical filament or laser.

The amount of CO in the output stream is monitored by a sensor. Using feedback on both the gas flow rate and the heat source, the amount of CO generated is controlled to match the prescribed, adjustable value.
P120148US01

Improving Drug Delivery with Boronic Acids

UW–Madison researchers have developed methods for boronating cargo molecules to mediate their entry into mammalian cells via the glycocalyx. ‘Cargo’ molecules include drugs, proteins, labels, amino acids or any other desired molecule.

Boronation methods include ligating, crosslinking or otherwise bonding phenylboronic acids/oligopeptides to the cargo molecule. It is believed that the boronates undergo complexation with glycans on the cell surface. This facilitates the molecule’s entry into cell endosomes, where the cargo is released by enzyme action.
P110315US02

GFAbs – GFP-Based Biosensors with the Binding Properties of Antibodies

UW-Madison researchers have developed a GFP-based scaffold that maintains its fluorescence properties in the presence of two inserted binding loops.  The scaffold is capable of accepting a diverse loop repertoire from which fluorescent binding proteins could be isolated.

Inserting multiple loops into the scaffold yields fluorescent biosensors known as GFAbs.  The researchers have developed expression libraries consisting of multiple fluorescent biosensors, which are capable of detecting and isolating antigens or other molecules of interest, to provide a resource for identifying binding ligands.
P09101US03

One-Step DNA Extraction from Dried Blood Spots for Newborn Screening

A Wisconsin researcher has developed a one-step method for eluting DNA from a blood sample. The method involves using a DNA elution solution and agitating the blood sample in the solution with heat. The purified DNA is suitable for use in techniques such as enzymatic DNA amplification and real-time PCR.
P100253US02

Treating X-Linked Hypophosphatemia (XLH), Bone Deformity and Other Renal Phosphate Wasting Disorders

UW–Madison researchers have developed methods to treat XLH, and potentially other renal phosphate wasting disorders, using polyarginine peptides. The peptides stimulate the 7B2-SPC2 protein complex, overcoming a primary abnormality resulting from the PHEX gene mutation responsible for the cascade of abnormal protein functions that lead to the XLH phenotype.

Administered alone or with other pharmaceutical agents, the arginine peptides work by enhancing FGF-23 degradation into inactive fragments and suppressing FGF-23 production. The resultant normalized levels of FGF-23 and other proteins completely rescue the HYP phenotype, including the abnormalities in the serum phosphate and bone mineralization.
P100323US02

Gravity- and Pressure-Controlled Valve System for Controlling Cerebrospinal Fluid in the Ventricular System

UW–Madison researchers have developed a system that allows drainage of excess CSF and prevents CSF overdrainage. A key insight is that cardiac pulsations can be transmitted inside the shunt tubing, creating a pulsatile pressure wave that propagates down the tubing. When this pressure wave hits a pressure differential valve, it can force the valve open during the systolic phase of the pressure wave, pumping some CSF through the valve with each systolic phase. In this way, CSF can be pumped across a valve as long as the peak pressure within the shunt tubing exceeds the preset pressure differential threshold for that valve, even if the mean pressure is below that same threshold. Overdrainage then occurs. The improved system and valve design prevent slit ventricle syndrome by addressing both gravity siphon effects and cardiac pulsations.

The improved system consists of tubing that leads from the ventricular system into a valve system that has two arms, a forward flow arm and a return flow arm. A one-way low threshold pressure differential valve is located in the forward flow arm. CSF that passes this first valve can either exit the valve system through a one-way higher threshold exit valve that leads into the peritoneal cavity, or it can flow through the return flow arm via a one-way low threshold valve that returns CSF back to the inlet side of the valve system. By choosing appropriate pressure differentials for the three valves, one can bracket the pressures on the inlet side between a set minimum and maximum value. If the ICP rises above the set maximum, then CSF will flow through the inlet valve and out the exit valve. If the ICP drops below the set minimum, then CSF will flow through the return valve and back towards the inlet side of the valve system, thus preventing overdrainage. The high threshold pressure differential exit valve also incorporates a gravity compensation unit that negates the gravity siphoning effect, regardless of the orientation of the patient. Thus, the net effect is to allow for drainage of excess CSF while preventing overdrainage due to either the cardiac pulsation or gravity siphon effect.
P110042US01

Algorithm Improves Resolution of Time-Frequency Analysis for Medical Diagnostics, Telecommunications

UW-Madison researchers have developed a pseudo-wavelet algorithm known as the “damped-oscillator oscillator detector” (DOOD). This algorithm is unique among all wavelet and pseudo-wavelet algorithms in that it is the only algorithm that is explicitly based on modeling data as a “driving force” that interacts with a hypothetical set of mathematical oscillators. In the DOOD algorithm, an entirely new spectral density can be defined as the time rate of change in the energy specifically due to interaction with the data driving force, referred to as the data power. The data power measure is more sensitive to the presence or absence of data oscillators than traditional energy measures.

The DOOD algorithm allows an enormous frequency range to be spanned over as many orders of magnitude as desired. The instantaneous phase of oscillation and correlation functions can be calculated easily. The inverse of the DOOD transform is accomplished readily, which means that the DOOD algorithm also can be used to compress data. Any time-frequency or correlation analysis that can be accomplished by conventional means also can be accomplished using the DOOD algorithm, with the advantages of greater flexibility in defining the frequency range and better time resolution.
P100227US01

Double-Strand DNA Break Repair in Vitro – Forensic and Genomic Applications

UW–Madison researchers have developed a method for the in vitro joining of two DNA fragments that have homologous DNA sequences through a simplified process of DNA double-strand break repair.  This approach enables the sequencing of poor quality or minimally available DNA that may be in a complex mixture of contaminating DNA sequences.  It requires only three proteins or their homologues: RecA protein, single-stranded DNA binding protein (SSB) and DNA polymerase I.  The proteins preferably are obtained from E. coli

In this method, a single-stranded DNA probe with some homology to the target DNA is combined with RecA protein and SSB.  Then the target duplex DNA molecule, which has a double-strand break and is not super-coiled, is added to the mixture.  The single-strand probe invades the doubled-stranded target DNA.  When DNA polymerase is added with dNTPs, it extends both strands to create a double-stranded DNA molecule in which the two fragments have joined.  PCR reactions then can be carried out using primers that bind the probe and target DNA.  This will allow amplification of STRs, if there are lesions in the DNA close to an STR.
P090366US02

Microfluidic Reaction Cell with Optical Tweezers for the Parallel Synthesis of Oligonucleotides

UW-Madison researchers have developed a combinatorial chemistry reaction cell for the parallel synthesis of chain molecules, including oligonucleotides. Contrary to the common practice of one oligo synthesized on many beads, this technology creates a “one bead, one oligo” scenario. 

The reaction cell is a microfluidic system that relies on the manipulation of solid-phase carrier particles such as porous glass beads in a multi-stream laminar flow.  It uses a strongly focused laser beam, known as “optical tweezers,” to capture and move particles back and forth across the streams.

The system includes two or more fluid streams with “particle holders” in each stream.  A fluid stream consists of inert chemicals that do not react with the particles.  For instance, the particles start in the holders of the first fluid stream and then are moved to the second fluid stream using optical tweezers.  The second fluid stream contains reactant molecules–DNA bases–that attach to oligos on the particles, extending the oligos by one base.   Then the particles are moved back to the original inert chemical fluid stream to allow the reactant chemicals in the second fluid stream to be changed.  At this point, the entire process is repeated to continue extending the nucleic acid chain.

The method allows the synthesis of multiple DNA sequences in a simple, microfluidics environment without a complex, structured substrate.  This reduces the amount of reagents needed, improving efficiency and reducing operating costs.  The particle holders also allow for the trapping of complex particle sets using only a single laser.  Therefore, the system is extremely useful for the synthesis of high-yield and high-complexity oligonucleotides that can be used to produce DNA microarrays for genomics, drug discovery, combinatorial chemistry and other applications.
P09069US

Computational Algorithms for Identifying, Suppressing and Reversing Epilepsy

UW-Madison researchers have developed a protocol that accounts for each of the conditions required for the development of epileptogenesis and determines a treatment to reverse, or “unlearn,” epilepsy.  Because this protocol addresses factors in addition to neuronal hyperexcitability, it may prove more effective than current methods. 

The new technique involves acquiring and analyzing neural activity data from a subject to determine epileptic patterns based on neuronal hyperexcitability, spatial connectivity and temporal connectivity.  Treatment using an electrical stimulus then is focused based on the determined patterns and administered to the subject.
P08298US

Improved Brain-Computer Interface Technology for Long-Term Cortical Stimulation or Recording

UW-Madison researchers have developed a thin-film microelectrode array that is tailored specifically for long-term, minimally invasive cortical recording or stimulation.  The array includes a new type of electrode, called a “micro-electrocorticographic (μECoG) electrode,” which is significantly smaller, more flexible and less invasive than existing brain recording or stimulating electrodes. 

The microelectrode array is implanted in the cranium of an individual in a contracted configuration.  Then a predetermined stimulus, such as voltage, causes a flexible element to unfurl the electrode structure to its expanded configuration.  An array of contacts, which is linked to a control module, is included on the flexible element.  These contacts engage the cortical surface to record or stimulate brain signals when the microelectrodes are in the expanded position.
P08317US

Improved Wound Healing Using Patterned Gradients of Immobilized Biomolecules

UW-Madison researchers have developed a wound dressing with a patterned gradient of immobilized growth factors to accelerate wound healing. To create a platform that promotes directed migration of cells during dermal wound healing, growth factors are immobilized on a substrate in a pattern of increasing growth factor concentration, with the highest concentration typically at the center of the dressing. Cells migrate toward greater concentrations of growth factor, and their speed is determined by the slope of the gradient. The surface may also include an extracellular matrix protein, such as collagen, fibronectin or laminin, and/or a factor that promotes the formation of blood vessels.
P07291US

Patient Support Bench and Method for Diagnosing Spinal Abnormalities with MRI

UW-Madison researchers have developed an improved technique for diagnosing spinal abnormalities that employs magnetic resonance imaging (MRI) -- a more accurate and precise technique for assessing vertebral slippage. In this technique, MRI images are captured before and after controlled rotation of the lower spine in order to determine the relative rotation of each vertebra. To facilitate the use of MRI in assessing spinal problems, the researchers designed a support bench for patients that provides graded and highly controlled rotation of the lumbar vertebrae while minimizing spinal bending -- both of which are key to accurate diagnosis.
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Please contact our technology commercialization team at licensing@warf.org or 608.263.2500 for more information.