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Tom Matula

Senior Principal Physicist

Affiliate Assistant Professor, Bioengineering and Affiliate Associate Professor, Electrical Engineering






B.S. Physics, California State University at Fresno, 1988

M.S. Physics, Washington State University, 1990

Ph.D. Physics, Washington State University, 1993


Sclerosing Foams Optimized with Ultrasound Preparation

Sclerotherapy is a procedure to treat varicose veins. uWAMIT researchers have discovered that ultrasound applied to therapeutic liquid solutions creates foams with smaller bubbles and a more uniform size distribution than traditional mechanical agitation methods. This technique may yield safer and more effective foam sclerosis treatments.

8 Jul 2016

Ultrasound Contrast Agents (Microbubbles) in the Microvasculature

High-speed images of oscillating micro-bubbles in small blood vessels are imaged to observe how the bubble oscillations might help induce permeation in the endothelium, allowing drugs to be transported across that barrier.

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23 Jan 2013

High-speed images of oscillating micro-bubbles in small blood vessels are imaged to observe how the bubble oscillations might help induce permeation in the endothelium, allowing drugs to be transported across that barrier.

We excise the mesentery, immerse it in a Krebs solution and place it on a microscope. A flash lamp is used to deliver enough light to obtain good images with 50 nsec exposure times. Microbubbles are perfused along with a saline solution. When a vessel is found containing microbubbles, the experiment is triggered, sending a very short ultrasound pulse (1 MHz) towards the tissue sample. 14 images are collected at pre-determined times (usually every 150 or 300 nsec). Quantification of the images gives us information about vessel deformations, bubble oscillations, and registration of the specific locations that are later used to correlate vessel motion with histological observations of vessel damage.


PIXUL: PIXelated ULtrasound Speeds Disease Biomarker Search

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26 Apr 2018

Accurate assessment of chromatin modifications can be used to improve detection and treatment of various diseases. Further, accurate assessment of chromatin modifications can have an important role in designing new drug therapies. This novel technology applies miniature ultrasound transducers to shear chromatin in standard 96-well microplates. PIXUL saves researchers hours of sample preparation time and reduces sample degradation.

Non-invasive Treatment of Abscesses with Ultrasound

Abscesses are walled-off collections of fluid and bacteria within the body. They are common complications of surgery, trauma, and systemic infections. Typical treatment is the surgical placement of a drainage catheter to drain the abscess fluid over several days. Dr. Keith Chan and researchers at APL-UW's Center for Industrial + Medical Ultrasound are exploring how to treat abscesses non-invasively, that is, from outside the body, with high-intensity focused ultrasound (HIFU). This experimental therapy could reduce pain, radiation exposure, antibiotic use, and costs for patients with abscesses. Therapeutic ultrasound could also treat abscesses too small or inaccessible for conventional drainage.

20 Jun 2016

Flow Cytometry Techniques Advance Microbubble Science

Researchers at the Center for Industrial and Medical Ultrasound (CIMU) are measuring the physical properties of ultrasound contrast agents — tiny gas bubbles several microns in diameter used to increase sonogram imaging efficiency in the body. When injected to the general circulation they can act as probes and beacons within the body, and can carry and deploy chemotherapeutic payloads.

CIMU researchers have developed a hybrid instrument that combines an off-the-shelf flow cytometer with an acoustic transducer. The cytometer's laser interrogation counts and measures the bubbles while the acoustic interrogation reveals the bubbles' viscosity and elasticity at megahertz frequencies.

5 Dec 2013

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2000-present and while at APL-UW

CryoGrid-PIXUL-RNA: high throughput RNA isolation platform for tissue transcript analysis

Schactler, S.A., and 10 others including T.J. Matula, "CryoGrid-PIXUL-RNA: high throughput RNA isolation platform for tissue transcript analysis," BMC Genomics, 24, doi:10.1186/s12864-023-09527-7, 2023.

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8 Aug 2023

Disease molecular complexity requires high throughput workflows to map disease pathways through analysis of vast tissue repositories. Great progress has been made in tissue multiomics analytical technologies. To match the high throughput of these advanced analytical platforms, we have previously developed a multipurpose 96-well microplate sonicator, PIXUL, that can be used in multiple workflows to extract analytes from cultured cells and tissue fragments for various downstream molecular assays. And yet, the sample preparation devices, such as PIXUL, along with the downstream multiomics analytical capabilities have not been fully exploited to interrogate tissues because storing and sampling of such biospecimens remain, in comparison, inefficient.

To mitigate this tissue interrogation bottleneck, we have developed a low-cost user-friendly system, CryoGrid, to catalog, cryostore and sample tissue fragments. TRIzol is widely used to isolate RNA but it is labor-intensive, hazardous, requires fume-hoods, and is an expensive reagent. Columns are also commonly used to extract RNA but they involve many steps, are prone to human errors, and are also expensive. Both TRIzol and column protocols use test tubes. We developed a microplate PIXUL-based TRIzol-free and column-free RNA isolation protocol that uses a buffer containing proteinase K (PK buffer). We have integrated the CryoGrid system with PIXUL-based PK buffer, TRIzol, and PureLink column methods to isolate RNA for gene-specific qPCR and genome-wide transcript analyses. CryoGrid-PIXUL, when integrated with either PK buffer, TRIzol or PureLink column RNA isolation protocols, yielded similar transcript profiles in frozen organs (brain, heart, kidney and liver) from a mouse model of sepsis.

RNA isolation using the CryoGrid-PIXUL system combined with the 96-well microplate PK buffer method offers an inexpensive user-friendly high throughput workflow to study transcriptional responses in tissues in health and disease as well as in therapeutic interventions.

Sonographic features of abscess maturation in a porcine model

Lotta, D.F., M. Bruce, Y.-N. Wang, J. Kucewicz, T.K. Khokhlova, K. Chan, W. Monsky, and T.J. Matula, "Sonographic features of abscess maturation in a porcine model," Ultrasound Med. Biol., 47, 1920-1930, doi:10.1016/j.ultrasmedbio.2021.03.011, 2021.

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1 Jul 2021

Abscesses are walled-off collections of infected fluids that often develop as complications in the setting of surgery and trauma. Treatment is usually limited to percutaneous catheterization with a course of antibiotics. As an alternative to current treatment strategies, a histotripsy approach was developed and tested in a novel porcine animal model. The goal of this article is to use advanced ultrasound imaging modes to extract sonographic features associated with the progression of abscess development in a porcine model. Intramuscular or subcutaneous injections of a bi-microbial bacteria mixture plus dextran particles as an irritant led to identifiable abscesses over a 2 to 3 wk period. Selected abscesses were imaged at least weekly with B-mode, 3-D B-mode, shear-wave elastography and plane-wave Doppler imaging. Mature abscesses were characterized by a well-defined core of varying echogenicity surrounded by a hypoechoic capsule that was highly vascularized on Doppler imaging. 3-D imaging demonstrated the natural history of abscess morphology, with the abscess becoming less complex in shape and increasing in volume. Furthermore, shear-wave elastography demonstrated variations in stiffness as phlegmon becomes abscess and then liquefies, over time. These ultrasound features potentially provide biomarkers to aid in selection of treatment strategies for abscesses.

Treating porcine abscesses with histotripsy: A pilot study

Matula, T.J., Y.-N. Wang, T. Khokhlova, D.F. Leotta, J. Kucewicz, A.A. Brayman, M. Bruce, A.D. Maxwell, B.E. MacConaghy, G. Thomas, V.P. Chernikov, S.V. Buravkov, V.A. Khokhlova, K. Richmond, K. Chan, W. Monsky, "Treating porcine abscesses with histotripsy: A pilot study," Ultrasound Med. Biol., 47, 603-619, doi:10.1016/j.ultrasmedbio.2020.10.011, 2021.

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1 Mar 2021

Infected abscesses are walled-off collections of pus and bacteria. They are a common sequela of complications in the setting of surgery, trauma, systemic infections and other disease states. Current treatment is typically limited to antibiotics with long-term catheter drainage, or surgical washout when inaccessible to percutaneous drainage or unresponsive to initial care efforts. Antibiotic resistance is also a growing concern. Although bacteria can develop drug resistance, they remain susceptible to thermal and mechanical damage. In particular, short pulses of focused ultrasound (i.e., histotripsy) generate mechanical damage through localized cavitation, representing a potential new paradigm for treating abscesses non-invasively, without the need for long-term catheterization and antibiotics. In this pilot study, boiling and cavitation histotripsy treatments were applied to subcutaneous and intramuscular abscesses developed in a novel porcine model. Ultrasound imaging was used to evaluate abscess maturity for treatment monitoring and assessment of post-treatment outcomes. Disinfection was quantified by counting bacteria colonies from samples aspirated before and after treatment. Histopathological evaluation of the abscesses was performed to identify changes resulting from histotripsy treatment and potential collateral damage. Cavitation histotripsy was more successful in reducing the bacterial load while having a smaller treatment volume compared with boiling histotripsy. The results of this pilot study suggest focused ultrasound may lead to a technology for in situ treatment of acoustically accessible abscesses.

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Ultrasound System for Shearing Cellular Material in a Microplate

Patent Number: 11,592,366

Tom Matula, Adam Maxwell


28 Feb 2023

Ultrasound System for Shearing Cellular Material in a Microplate

Patent Number: 10,809,166

Tom Matula, Brian MacConaghy, Adam Maxwell

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20 Oct 2020

Disclosed embodiments include illustrative piezoelectric element array assemblies, methods of fabricating a piezoelectric element array assembly, and systems and methods for shearing cellular material. Given by way of non-limiting example, an illustrative piezoelectric element array assembly includes at least one piezoelectric element configured to produce ultrasound energy responsive to amplified driving pulses. A lens layer is bonded to the at least one piezoelectric element. The lens layer has a plurality of lenses formed therein that are configured to focus ultrasound energy created by single ones of the at least one piezoelectric element into a plurality of wells of a microplate disposable in ultrasonic communication with the lens layer, wherein more than one of the plurality of lenses overlie single ones of the at least one piezoelectric element.

Methods for Separating, Concentrating, and/or Differentiating Between Cells from a Cell Sample

Patent Number: 10,794,827

Tom Matula, Oleg Sapozhnikov, Brian MacConaghy

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6 Oct 2020

Embodiments are generally related to differentiating and/or separating portions of a sample that are of interest from the remainder of the sample. Embodiments may be directed towards separating cells of interest from a cell sample. In some embodiments, acoustic impedances of the cells of interest may be modified. For example, the acoustic properties of the cells of interest may be modified by attaching bubbles to the cells of interest. The cell sample may then be subjected to an acoustic wave. The cells of interest may be differentiated and/or separated from the remainder of the sample based on relative displacements and/or volumetric changes experienced by the cells of interest in response thereto. The cells of interest may be separated using a standing wave and sorted into separate channels of a flow cell. Optionally, the cells may be interrogated by a light source and differentiated by signals generated in response thereto.

More Inventions

Acoustics Air-Sea Interaction & Remote Sensing Center for Environmental & Information Systems Center for Industrial & Medical Ultrasound Electronic & Photonic Systems Ocean Engineering Ocean Physics Polar Science Center