New Inventions

Algorithms to Classify T Cell Activation by Autofluorescence Imaging

Building on award-winning work, UW–Madison researchers have discovered that autofluorescence intensity images of NAD(P)H can accurately classify T cells as activated or not activated (‘naïve’ or ‘quiescent’), and have developed algorithms to classify T cell activation based on the images. Specifically, adapting pre-trained convolutional neural networks (CNNs) for the T cell activity classification task, T cells can be classified with 92 percent accuracy. These pre-trained CNNs perform better than classification based on summary statistics (e.g., cell size) or CNNs trained on the autofluorescence images alone.

This invention provides a way to non-invasively detect T cell activation by imaging NAD(P)H intensity. These algorithms can be applied to NAD(P)H images taken with commercial imaging flow cytometers / sorters, and fluorescence microscopes. If increased accuracy of T cell activation is needed for a specific application, additional measurements of the other NAD(P)H and FAD fluorescence endpoints can be obtained and used for classification.
(Aug 13, 2020) P190306US02

Stimuli-Responsive Smart Block Copolymers Improve Dispersion of Titanium Dioxide in Architectural Coatings

An associate professor of materials science and engineering at the University of Wisconsin-Eau Claire has synthesized a series of stimuli-responsive block copolymer dispersants optimized for use in architectural coating applications. These novel polymer dispersants are currently being developed as additives to existing coatings for improved dispersion of TiO2. Dispersant properties are tunable through modification of the polymer composition as a function of pH and temperature. Initial data shows that the addition of these polymers can decrease settling rate, control viscosity, and control interfacial activity, all of which are important for greater dispersant effectiveness and stability over time. These polymers have demonstrated the ability to interface with pigment particles, such as TiO2, resulting in improved dispersion of the pigment. Initial testing shows reduced TiO2 concentration while maintaining zero shear viscosity and shear thinning properties, which prevents drips in the coatings, and is comparable to commercially available formations. These properties are tunable and may be altered to tailor the product for a desired use or environment, or to readjust the properties of an aged existing product. New methods of synthesis to allow for the scaled-up production of these polymer additives are complete and new purification methods are in progress. Further development will also focus on maintaining additional properties like coverage and opacity, and testing of additional polymer compositions and particle surface coatings.
(Jul 22, 2020) T200004WO01

W8405-1R: A Red Skin White Flesh Potato for the Fresh Market

UW–Madison researchers have developed W8405-1R, a red potato variety with very smooth and uniform tubers, round-oval shape, shallow eyes and attractive coloring that maintains well in storage.

The new variety is available through the Wisconsin Crop Improvement Association.
(Jan 2, 2020) P120384US01

Gene Correction of Pompe Disease and Other Autosomal Recessive Disorders via CRISPR and other RNA-Guided Nucleases

UW–Madison researchers have developed a complexed CRISPR-Cas system (S1mplex; P170309US01) for treating patients with inherited autosomal recessive conditions. The work focuses on Pompe disease. The inventors identified new guide RNA target sites and repair templates that could be used for gene therapy strategies and cell therapeutic strategies.

The inventors demonstrated successful editing of fibroblast and induced pluripotent stem cells from three Pompe patients at UW Hospital having heterozygous mutations (each allele containing a different mutation, both leading to loss of function of the enzyme). Using their complexed CRISPR-Cas technology markedly increased editing precision (18.4-fold) in two different cell lines (HEK and hPSC), easing concerns about off-target effects. Importantly, rapid glycogen processing improvements were observed after gene correction – 24 hours and 96 hours, respectively.
(Nov 5, 2019) P190021US02

Oligolactic Acid-Paclitaxel and Oligolactic Acid-Docetaxel Prodrugs for Injection

UW–Madison researchers have developed oligolactic acid prodrugs based on PTX, DTX, rapamycin and selumetinib for PEG-PLA micelles for injection.
  • Oligolactic acid acts as a compatibilizer between anticancer drugs and PEG-PLA micelles, resulting in enhanced drug loading, physical stability and controlled release.
  • Oligolactic acid prodrugs are stable in PEG-PLA micelles and upon release convert back into parent drug by a combination of “backbiting” and esterase-based hydrolysis rather than by random hydrolysis.
  • Oligolactic acid-PTX prodrug injected in PEG-PLA micelles has higher plasma exposure than PTX injected in PEG-PLA micelles at an equivalent dose.
  • Oligolactic acid-PTX prodrug injected in PEG-PLA micelles has higher antitumor efficacy than PTX injected in PEG-PLA micelles at an equivalent dose.
  • Oligolactic acid-rapamycin prodrug injected in PEG-PLA micelles has higher antitumor efficacy than rapamycin injected in PEG-PLA micelles at an equivalent dose.
(Oct 25, 2019) P160169US03

Platform for High-Throughput Analysis of Microbial Interactions

UW–Madison researchers have developed a research tool for large-scale mapping of interactions in microbiomes. Their method employs gene sequencing in a microfluidic system to increase throughput by several orders of magnitude (1,000-10,000 times).

Specifically, the researchers mixed groups of several species of bacteria in culture. They encapsulated cells into millions of picoliter droplets dispersed in an oil phase. The droplets were incubated to allow the microbes to interact, assemble into a community and perform functional activities. After incubation, the composition of the community within the droplet was analyzed using fluorescence microscopy or next-generation DNA sequencing.

The presence or absence of microbes in a drop can be indicative of different species preferentially interacting with other species in the bulk culture or droplet, and can be used to reconstruct the microbiome’s ecological network.
(Oct 25, 2019) P190033US02

Semiconductor Quantum Dot Computer-Aided Engineering (CAE) Simulation Tool

A Professor of Electrical Engineering at the University of Wisconsin – Platteville has developed a software simulation tool for the computer aided engineering (CAE) of Quantum Dots. The CAE simulation tool accepts input of the QD parameters and then computes and returns the resulting optical and electronic properties. This includes QD structures with an InAs core and a GaAs matrix, and can be extended to any III-IV materials. The CAE tool simulates the most popular pyramidal and half-ellipsoidal QD shapes and can be extended to any arbitrary geometric shape. Compared with the often-incomplete results reported in the literature, this CAE simulation tool returns all possible electronic states within the QD. The CAE simulation results also supported the experimental data for the corresponding QD. The simulation tool currently runs as an application in the COMSOL platform and does not require a supercomputer for calculations and processing.
(Oct 22, 2019) T180055US02

Bacterial Membrane Nanoparticles as an Immunotherapy System for Cancer Treatment

UW–Madison researchers have engineered a bacterial membrane-coated nanoparticle (BNP) capable of acting as a cancer treatment/vaccine. The BNP consists of a nanosized polyplex made up of a PC7A polymer, a CpG oligonucleotide inside the bacterial membrane and surface attached maleimide (Mal) groups. PC7A provides both a pH responsiveness, which allows for membrane interactions at neutral pH, and subsequent endosomal escape once internalized into the cell. CpG functions as an immunostimulatory molecule (as a toll-like receptor agonist). And Mal groups decorate the surface of the BNP to capture tumor remnants created by radiation treatment, accelerating cellular recognition of the tumor.

In combination with radiation therapy, the inventors show that BNP treatment led to significant tumor growth suppression and enhanced survival rate in a model of a B78 melanoma tumor, a hard cancer to treat. By enabling patients’ immune systems to recognize the unique antigens on their own tumors, this combination therapy may represent a universal approach to achieve personalized cancer immunotherapy using off-the-shelf agents.
(Sep 5, 2019) P180331US02

Method and Device to Screen and Sort Cancer Immunotherapy Cells

UW–Madison researchers have developed a highly accurate label-free method to non-invasively detect T cell activation by detection of free-NAD(P)H fraction, NAD(P)H α1. NAD(P)H α1 can be measured by fluorescence lifetime imaging or spectroscopy systems. The device could also sort T cells based on NAD(P)H α1. If increased accuracy of T cell activation is needed for a specific application, additional measurements of the other NAD(P)H and FAD autofluorescence endpoints can be obtained and used for classification.
(Aug 28, 2019) P180292US02

Novel Catalysts for Improved Remediation of Sulfur-Containing Pollutants

A professor of chemistry at the University of Wisconsin-La Crosse has developed a versatile suite of iron-based catalysts with the potential to promote rapid, efficient oxidation of deleterious sulfur-containing compounds present in crude oil, natural gas, and/or aqueous waste streams. With these novel catalysts, there is no need for corrosive base, elevated temperatures, expensive or dangerous oxidants, or high pressures.
(Aug 20, 2019) T190005WO01