Thomas P. Ryan

Overview of plasma technology used in medicine

Plasma Medicine is a growing field that is having an impact in several important areas in therapeutic patient care, combining plasma physics, biology, and clinical medicine. Historically, plasmas in medicine were used in electrosurgery for cautery and non-contact hemostasis. Presently, non-thermal plasmas have attained widespread use in medicine due to their effectiveness and compatibility with biological systems. The paper will give a general overview of how low temperature, non-equilibrium, gas plasmas operate, both from physics and biology perspectives. Plasma is commonly described as the fourth state of matter and is typically comprised of charged species, active molecules and atoms, as well as a source of UV and photons. The most active areas of plasma technology applications are in wound treatment; tissue regeneration; inactivation of pathogens, including biofilms; treating skin diseases; and sterilization. There are several means of generating plasmas for use in medical applications, including plasma jets, dielectric barrier discharges, capacitively or inductively coupled discharges, or microplasmas. These systems overcome the former constraints of high vacuum, high power requirements and bulky systems, into systems that use room air and other gases and liquids at low temperature, low power, and hand-held operation at atmospheric pressure. Systems will be discussed using a variety of energy sources: pulsed DC, AC, microwave and radiofrequency, as well as the range of frequency, pulse duration, and gas combinations in an air environment. The ionic clouds and reactive species will be covered in terms of effects on biological systems. Lastly, several commercial products will be overviewed in light of the technology utilized, health care problems being solved, and clinical trial results.

Utility and translatability of mathematical modeling, cell culture and small and large animal models in magnetic nanoparticle hyperthermia cancer treatment research

For more than 50 years, hyperthermia-based cancer researchers have utilized mathematical models, cell culture studies and animal models to better understand, develop and validate potential new treatments. It has been, and remains, unclear how and to what degree these research techniques depend on, complement and, ultimately, translate accurately to a successful clinical treatment. In the past, when mathematical models have not proven accurate in a clinical treatment situation, the initiating quantitative scientists (engineers, mathematicians and physicists) have tended to believe the biomedical parameters provided to them were inaccurately determined or reported. In a similar manner, experienced biomedical scientists often tend to question the value of mathematical models and cell culture results since those data typically lack the level of biologic and medical variability and complexity that are essential to accurately study and predict complex diseases and subsequent treatments. Such quantitative and biomedical interdependence, variability, diversity and promise have never been greater than they are within magnetic nanoparticle hyperthermia cancer treatment. The use of hyperthermia to treat cancer is well studied and has utilized numerous delivery techniques, including microwaves, radio frequency, focused ultrasound, induction heating, infrared radiation, warmed perfusion liquids (combined with chemotherapy), and, recently, metallic nanoparticles (NP) activated by near infrared radiation (NIR) and alternating magnetic field (AMF) based platforms. The goal of this paper is to use proven concepts and current research to address the potential pathobiology, modeling and quantification of the effects of treatment as pertaining to the similarities and differences in energy delivered by known external delivery techniques and iron oxide nanoparticles.

A tutorial on recent advances in Thermal Therapy Systems

Thermal therapy as a treatment for cancer is a dynamic treatment epicenter, with a variety of technologies available and undergoing continuous improvement. Recent advances in technology and applications for thermal therapy give clinicians more power to affect larger volumes of tissue in less time. New radiofrequency (RF) and microwave (MW) systems have appeared recently, giving powerful tools for cancer therapy. Novel therapeutic ultrasound (US) technologies are being explored, but are presently not commercialized. Thermal therapy applicators that deliver power to the target in the patient will be reviewed for shape, size, and features. The operation and performance of various applicators will be discussed. In the goal of performance increase, several features have been commercialized in the evolution of the technology, including cooling, multiple applicator arrays, power modulation, and applicator deployment and shape change. To place recent progress into perspective, a historical review of some RF and MW applicators will be given. The work will cover modeling and simulations, as well as in-vitro, in-vivo, and clinical results.

Developing an open platform for evidence-based microwave ablation treatment planning and validation

The clinical utility of current thermal ablation planning tools is severely limited by treatment variability. We discuss the development of an open platform for evidence-based thermal ablation treatment planning and validation. Improved predictive treatment modeling and consistent outcome analysis are crucial components for useful planning and guidance tools.

Histological evaluation and optimization of surgical vessel sealing systems

Surgical vessel sealing systems are widely used to achieve hemostasis and dissection in open surgery and minimally invasive, laparoscopic surgery. This enabling technology was developed about 17 years ago and continues to evolve with new devices and systems achieving improved outcomes. Histopathological assessment of thermally sealed tissues is a valuable tool for refining and comparing performance among surgical vessel sealing systems. Early work in this field typically assessed seal time, burst rate, and failure rate (in-situ). Later work compared histological staining methods with birefringence to assess the extent of thermal damage to tissues adjacent to the device. Understanding the microscopic architecture of a sealed vessel is crucial to optimizing the performance of power delivery algorithms and device design parameters. Manufacturers rely on these techniques to develop new products. A system for histopathological evaluation of vessels and sealing performance was established, to enable the direct assessment of a treatment’s tissue effects. The parameters included the commonly used seal time, pressure burst rate and failure rate, as well as extensions of the assessment to include its likelihood to form steam vacuoles, adjacent thermal effect near the device, and extent of thermally affected tissue extruded back into the vessel lumen. This comprehensive assessment method provides an improved means of assessing the quality of a sealed vessel and understanding the exact mechanisms which create an optimally sealed vessel.

Overview of current applications in plasma medicine

Plasma medicine is a rapidly growing field of treatment, with the number and type of medical applications growing annually, such as dentistry, cancer treatment, wound treatment, Antimicrobial (bacteria, biofilm, virus, fungus, prions), and surface sterilization. Work promoting muscle and blood vessel regeneration and osteointegration is being investigated. This review paper will cover the latest treatments using gas-based plasmas in medicine. Disinfection of water and new commercial systems will also be reviewed, as well as vaccine deactivation. With the rapid increase in new investigators, development of new devices and systems for treatment, and wider clinical applications, Plasma medicine is becoming a powerful tool in in the field of medicine. There are a wide range of Plasma sources that allows customization of the effect. These variations include frequency (DC to MHz), voltage capacity (kV), gas source (He, Ar; O2, N2, air, water vapor; combinations), direct/indirect target exposure, and water targets.

Corrosion and wear in plasma electrosurgical devices

Data were previously reported on studies of the effects of electrical discharges on the corrosion and wear of simple, single-wire test devices immersed in isotonic saline 1 . This work showed that there are a wide variety of mechanisms that can explain various aspects of electrode mass loss, even with very simple electrode geometries and operating conditions. It was found that the electrode material composition played an important role. Subsequently, our studies were expanded to include more realistic device geometries and operating conditions. This paper shows the results of studies on wear characteristics of electrodes made from a variety of highly corrosion resistant metals and alloys, including Waspaloy, Hastelloy, Inconel, Havar, Monel, and other pure metals such as Hafnium. All of these metals underwent wear testing under clinically relevant conditions. Depending on the operating conditions, multiple discrete physical and chemical effects were observed at different locations on the surface of an individual millimeter-scale device electrode. Scanning electron microscope (SEM) micrographs, Energy-dispersive X-ray spectroscopy (EDS) and area loss data will be presented for a variety of test conditions and electrode materials.

Antimicrobial outcomes in plasma medicine

Plasma is referred to as the fourth state of matter and is frequently generated in the environment of a strong electric field. The result consists of highly reactive species--ions, electrons, reactive atoms and molecules, and UV radiation. Plasma Medicine unites a number of fields, including Physics, Plasma Chemistry, Cell Biology, Biochemistry, and Medicine. The treatment modality utilizes Cold Atmospheric Plasma (CAP), which is able to sterilize and treat microbes in a nonthermal manner. These gas-based plasma systems operate at close to room temperature and atmospheric pressure, making them very practical for a range of potential treatments and are highly portable for clinical use throughout the health care system. The hypothesis is that gas based plasma kills bacteria, fungus, and viruses but spares mammalian cells. This paper will review systematic work which shows examples of systems and performance in regards to antimicrobial effects and the sparing of mammalian cells. The mechanism of action will be discussed, as well as dosing for the treatment of microbial targets, including sterilization processes, another important healthcare need. In addition, commercial systems will be overviewed and compared, along with evidence-based, patient results. The range of treatments cover wound treatment and biofilms, as well as antimicrobial treatment, with little chance for resistance and tolerance, as in drug regimens. Current clinical studies include applications in dentistry, food treatment, cancer treatment, wound treatment for bacteria and biofilms, and systems to combat health care related infections.

The differing behavior of electrosurgical devices made of various electrode materials operating under plasma conditions

Coblation® is an electrosurgical technology which employs electrically-excited electrodes in the presence of saline solution to produce a localized and ionized plasma that can cut, ablate, and otherwise treat tissues for many different surgical needs. To improve our understanding of how Coblation plasmas develop from devices made from different electrode materials we describe several experiments designed to elucidate material effects. Initial experiments studied simple, noncommercial cylindrical electrode test devices operating in buffered isotonic saline without applied suction. The applied RF voltage, approximately 300 V RMS, was sufficient to form glow discharges around the active electrodes. The devices exhibited significantly different operating characteristics, which we ascribe to the differing oxidation tendencies and other physical properties of the electrode materials. Parameters measured include RMS voltage and current, instantaneous voltage and current, temporally-resolved light emission and optical emission spectra, and electrode mass-loss measurements. We correlate these measured properties with some of the bulk characteristics of the electrode materials such as work functions, standard reduction potentials and sputter yields.

Clinical applications of plasma based electrosurgical systems

Over the past 18 years, several electrosurgical systems generating a low temperature plasma in an aqueous conductive solution have been commercialized for various clinical applications and have been used in over 10 million patients to date. The most popular utilizations are in arthroscopic surgery, otorhinolaryngology surgery, spine and neurosurgery, urology and wound care. These devices can be configured to bring saline to the tip and to have concomitant aspiration to remove by-products and excess fluid. By tuning the electrode geometry, waveform and fluid dynamic at the tip of the devices, tissue resection and thermal effects can be adjusted individually. This allows one to design products that can operate as precise tissue dissectors for treatment of articular cartilage or debridement of chronic wounds, as well as global tissue debulking devices providing sufficient concomitant hemostasis for applications like tonsillectomies. Effects of these plasma based electrosurgical devices on cellular biology, healing response and nociceptive receptors has also been studied in various models. This talk will include a review of the clinical applications, with product descriptions, results and introductory review of some of the research on the biological effects of these devices.