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Tom Matula

Senior Principal Physicist

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

Email

matula@apl.washington.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

Ultrasound-based cell sorting with microbubbles: A feasibility study

Matula, T.J. O.A. Sapozhnikov, L.A> Ostrovsky, A.A. Brayan, J. Kocewicz, B.E. MacConaghy, and D. De Raad, "Ultrasound-based cell sorting with microbubbles: A feasibility study," J. Acoust. Soc. Am., 144, doi:10.1121/1.5044405, 2018.

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1 Jul 2018

The isolation and sorting of cells is an important process in research and hospital labs. Most large research and commercial labs incorporate fluorescently or magnetically labeled antibodies adherent to cell surface antigens for cell identification and separation. In this paper, a process is described that merges biochemical labeling with ultrasound-based separation. Instead of lasers and fluorophore tags, or magnets and magnetic particle tags, the technique uses ultrasound and microbubble tags. Streptavidin-labeled microbubbles were mixed with a human acute lymphoblastic leukemia cell line, CCL 119, conjugated with biotinylated anti-CD7 antibodies. Tagged cells were forced under ultrasound, and their displacement and velocity quantified. Differential displacement in a flow stream was quantified against erythrocytes, which showed almost no displacement under ultrasound. A model for the acoustic radiation force on the conjugated pairs compares favorably with observations. This technology may improve on current time-consuming and costly purification procedures.

Inactivation of planktonic Escherichia coli by focused 2-MHz ultrasound

Brayman, A.A., B.E. MacConaghy, Y.-N. Wang, K.T. Chan, W.L. Monsky, A.J. McClenny, and T.J. Matula, "Inactivation of planktonic Escherichia coli by focused 2-MHz ultrasound," Ultrasound Med. Biol., 43, 1476-1485, doi:10.1016/j.ultrasmedbio.2017.03.009, 2017.

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1 Jul 2017

This study was motivated by the desire to develop a non-invasive means to treat abscesses, and represents the first steps toward that goal. Non-thermal, high-intensity focused ultrasound (HIFU) was used to inactivate Escherichia coli (~1 x 109

Histotripsy liquefaction of large hematomas

Khokhlova, T.D., W.L. Monsky, Y.A. Haider, A.D. Maxwell, Y.-N. Wang, and T.J. Matula, "Histotripsy liquefaction of large hematomas," Ultrasound Med. Biol., 42, 1491-1498, doi:10.1016/j.ultrasmedbio.2016.01.020, 2016.

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1 Jul 2016

Intra- and extra-muscular hematomas result from repetitive injury as well as sharp and blunt limb trauma. The clinical consequences can be serious, including debilitating pain and functional deficit. There are currently no short-term treatment options for large hematomas, only lengthy conservative treatment. The goal of this work was to evaluate the feasibility of a high intensity focused ultrasound (HIFU)-based technique, termed histotripsy, for rapid (within a clinically relevant timeframe of 15–20 min) liquefaction of large volume (up to 20 mL) extra-vascular hematomas for subsequent fine-needle aspiration. Experiments were performed using in vitro extravascular hematoma phantoms—fresh bovine blood poured into 50 mL molds and allowed to clot. The resulting phantoms were treated by boiling histotripsy (BH), cavitation histotripsy (CH) or a combination in a degassed water tank under ultrasound guidance. Two different transducers operating at 1 MHz and 1.5 MHz with f-number = 1 were used. The liquefied lysate was aspirated and analyzed by histology and sized in a Coulter Counter. The peak instantaneous power to achieve BH was lower than (at 1.5 MHz) or equal to (at 1 MHz) that which was required to initiate CH. Under the same exposure duration, BH-induced cavities were one and a half to two times larger than the CH-induced cavities, but the CH-induced cavities were more regularly shaped, facilitating easier aspiration. The lysates contained a small amount of debris larger than 70 μm, and 99% of particulates were smaller than 10 μm. A combination treatment of BH (for initial debulking) and CH (for liquefaction of small residual fragments) yielded 20 mL of lysate within 17.5 minutes of treatment and was found to be most optimal for liquefaction of large extravascular hematomas.

More Publications

Inventions

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

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.

Patent Number: 9,645,080

Tom Matula, Andrew Brayman, Oleg Sapozhnikov, Brian MacConaghy, Jarred Swalwell, Camilo Perez

Patent

9 May 2017

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

Patent Number: 9,645,080

Tom Matula, Andrew Brayman, Oleg Sapozhnikov, Brian MacConaghy, Jarred Swalwell, Camilo Perez

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Patent

9 May 2017

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.

Dynamic Characterization of Particles with Flow Cytometry

Patent Number: 8,264,683

Tom Matula, Jarred Swalwell

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Patent

11 Sep 2012

Flow cytometry concepts are modified to enable dynamic characterizations of particles to be obtained using optical scattering data. Particles in flow will be introduced into a sample volume. Light scattered by a particle in the sample volume is collected and analyzed. What differentiates the concepts disclosed herein from conventional flow cytometry is the use of an acoustic source that is disposed to direct acoustic energy into the sample volume. As the particle passes through the sample volume, it responds to the acoustic energy, causing changes in the light scattered by the particle. Those changes, which are not measured during conventional flow cytometry, can be analyzed to determine additional physical properties of the particle.

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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