Bomsztyk lab receives three new U.S. patents for tools to accelerate research

Dr. Karol Bomsztyk is a professor of medicine (Allergy and Infectious Diseases), an adjunct professor in the departments of bioengineering and pharmacology, and a faculty member in the Institute for Stem Cell and Regenerative Medicine (ISCRM). His lab develops tools to help researchers understand what goes wrong inside cells as people age or when they develop diseases like cancer, diabetes, and kidney disease — and to use that information to help create better tools for diagnostics and treatments.

A major area of interest for the lab has been epigenetics – the system that controls when genes are turned on or off. Even though nearly every cell in the body contains the same DNA, cells look and behave differently because different genes are activated in different situations. All of this adds up to a vast amount of information to sift through in the quest for clarity about the origins of disease – and how it affects a unique individual.

The Bomsztyk Lab develops technologies that let scientists analyze hundreds or even thousands of biological signals simultaneously. They combine information from DNA, RNA, proteins, metabolites and chemical modifications inside cells — an approach often called “multi-omics.” The goal is to create a much more complete picture of disease biology.

The need for high-throughput technologies is only increasing as the field of medicine recognizes the high degree of variation possible in tumors, even from an individual patient, and shifts from relying on single-sample biopsies to multiple samples, which can lead to more effective treatments, but requires far more analysis.

In recent years, the lab has invented several high-throughput research tools and robotic workflows that allow scientists to process large numbers of tissue samples quickly and consistently.

These include one system called CryoGrid, for storing and sampling tissues, and a 96-well plate PIXUL instrument for preparing samples for genetic, epigenetic, transcriptomic, proteomic and metabolomic analysis. These multi-omics technologies help researchers to study human tissues more efficiently and to generate harmonized (i.e. from the same sample) large datasets that can be analyzed using machine learning and other computational tools.

The CryoGrid system was described in two articles published in 2023. One write-up appeared in the journal BMC Genomics. The first author of that paper, Scott Schactler, worked as a research scientist in the Bomsztyk Lab and is now a UW Pharmacology PhD candidate as well as a recent recipient of an ISCRM Fellowship. Daniel Mar, who is currently a research scientist in the lab, is the first author of the other paper, which was published in the journal Laboratory Investigation.

New patents

Now, Dr. Bomsztyk, his team, and their collaborators at Matchstick Technologies, a UW startup company, have recently received several patents for a set of tools that represent an upgrade to these high-throughput systems.

The centerpiece of this toolset is a next-generation version of the PIXUL, a 96-well thermosonicator dubbed the PIXUL H&C (for heating and cooling), that will allow researchers around the world to use high intensity focused ultrasound (HIFU) and heat – either separately or together (for example, by cycling between the two modalities) to analyze a wide range of tissues and other biological specimens with unprecedented detail.

Traditional sonicators generate sound waves that pass through a liquid medium and breakdown and mix microscopic biological materials, including proteins, DNA, and other structures. Introducing an option to apply heat and ultrasound at the same time gives researchers a new dial to turn – providing greater control, accuracy, and efficiency as they attempt to understand why diseases affect people differently, how to diagnose and treat diseases more effectively, and to use big data for personalized medicine.

Bomsztyk draws on an ancient analogy to describe the significance of incorporating heat to this modern technology.

“Humans have used heat to extract substances since the discovery of fire,” he says. “Cooking transforms the chemical composition of foods, breaks down cell walls, and unlocks nutrients and flavors. Espresso and cappuccino machines work in similar fashions. In our case, we want to apply the same principles to the millions of biospecimens that are sitting in drawers and freezers all around the world, waiting to be studied.”

But how best to extract samples from the preserved tissues? The second patent offers a solution that mimics the way geologists or engineers might remove sections of sediment for closer examination.

The hand-held equivalent in this case is a tissue sample coring system that allows researchers to drill into tissues at a desired depth and then eject cores of a specimen directly into a well of a PIXUL plate for extracting DNA, chromatin, RNA, protein, and metabolites.

The third patent is for a tool to help researchers with another part of the workflow that centers around the PIXUL Thermosonicator: moving the plate that holds those 96 wells of tissue samples.

“Normally people use their fingers to carry plates,” explains Bomsztyk. “But this method is awkward for the PIXUL and can lead to unsafe spills. So, I went to Lowe’s tool section to get ideas for a solution, which is a plate handle.”

The plate handling device Bomsztyk has patented has a grip and an expanding base to make it compatible with the microwell plates of various shapes and sizes that are used in research and diagnostic fields. The goal of the suite of Plate Handles is to protect lab technicians and to avoid contamination of tissue samples – more opportunities to improve the accuracy and efficiency of tissue analysis and to accelerate the study of disease.

While prototypes exist for all three devices, additional work and funding will be needed to bring the products to market. Still Bomsztyk is excited about the potential of the upgraded toolset to help researchers everywhere speed up the process of studying, diagnosing, and treating disease.

Patent Numbers

PIXUL H&C: US-12611645
CryoCore: US-12625038
PlateHandle: US-12472643