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Tom Matula

Senior Principal Physicist

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

Email

matula@uw.edu

Phone

206-685-7654

Education

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

M.S. Physics, Washington State University, 1990

Ph.D. Physics, Washington State University, 1993

Projects

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.

Videos

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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Publications

2000-present and while at APL-UW

Comparative study of histotripsy pulse parameters used to inactivate Escherichia coli in suspension

Ambedkar, P.A., Y.-N. Wang, T. Khokhlova, M. Bruce, D.F. Leotta, S. Totten, A.D. Maxwell, K.T. Chan, W.C. Liles, E.P. Dellinger, W. Monsky, A.A. Adedipe, and T.J. Matula, "Comparative study of histotripsy pulse parameters used to inactivate Escherichia coli in suspension," Ultrasound Med. Biol., 49, 2451-2458, doi:10.1016/j.ultrasmedbio.2023.08.004, 2023.

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1 Dec 2023

Bacterial loads can be effectively reduced using cavitation-mediated focused ultrasound, or histotripsy. In this study, gram-negative bacteria (Escherichia coli) in suspension were used as model bacteria to evaluate the effectiveness of two regimens of histotripsy treatments: cavitation histotripsy (CH) and boiling histotripsy (BH).

The results of this study suggest that both CH and BH can be used to inactivate E. coli in suspension, with the optimal regimen depending on the attainable peak negative focal pressure at the target.

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.

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Inventions

Real-Time Cell-Surface Marker Detection

Cell-separation systems and methods utilizing cell-specific microbubble tags and ultrasound-based separation are described. The methods are useful for simplification of time consuming and costlyu cell purification procedures and real time apoptosis detection.

Patent Number: 11,698,364

Tom Matula, Oleg Sapozhnikov

Patent

11 Jul 2023

Ultrasound System for Shearing Cellular Material in a Microplate

Patent Number: 11,592,366

Tom Matula, Adam Maxwell

Patent

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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Patent

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.

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
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