THz in biology and medicine: toward quantifying and understanding the interaction of millimeter- and submillimeter-waves with cells and cell processes

As the application and commercial use of millimeter- and submillimeter-wavelength radiation become more widespread, there is a growing need to understand and quantify both the coupling mechanisms and the impact of this long wavelength energy on biological function. Independent of the health impact of high doses of radio frequency (RF) energy on full organisms, which has been extensively investigated, there exists the potential for more subtle effects, which can best be quantified in studies which examine real-time changes in cellular functions as RF energy is applied. In this paper we present the first real time examination of RF induced changes in cellular activity at absorbed power levels well below the existing safe exposure limits. Fluorescence microscopy imaging of immortalized epithelial and neuronal cells in vitro indicate increased cellular membrane permeability and nanoporation after short term exposure to modest levels (10-50 mW/cm2) of RF power at 60 GHz. Sensitive patch clamp measurements on pyramidal neurons in cortical slices of neonatal rats showed a dramatic increase in cellular membrane permeability resulting either in suppression or facilitation of neuronal activity during exposure to sub-μW/cm2 of RF power at 60 GHz. Non-invasive modulation of neuronal activity could prove useful in a variety of health applications from suppression of peripheral neuropathic pain to treatment of central neurological disorders

Thermal Monitoring: Raman Spectrometer System for Remote Measurement of Cellular Temperature on a Microscopic Scale

A simple setup was demonstrated for remote temperature monitoring of water, water-based media, and cells on a microscopic scale. The technique relies on recording changes in the shape of a stretching band of the hydroxyl group in liquid water at 3,100-3,700 cm^(-1). Rather than direct measurements in the near-infrared (IR), a simple Raman spectrometer setup was realized. The measured Raman shifts were observed at near optical wavelengths using an inverted microscope with standard objectives in contrast to costly near-IR elements. This allowed for simultaneous visible inspection through the same optical path. An inexpensive 671-nm diode pump laser (<100 mW), standard dichroic and lowpass filters, and a commercial 600-1,000 nm spectrometer complete the instrument

Impact of Low Intensity Millimeter-Waves on Cell Membrane Permeability

As the applications and commercial uses of millimeter- and submillimeter-waves grow, we should take a more detailed look at the impact this frequency range has on biological systems. This paper examines one specific effect of low-level (10-50 times the MPE - maximum permissible exposure) 60 GHz CW RF power on cells – the opening of voltage sensitive cation channels

Can Neurons Sense Millimeter Waves?

The applications and commercial use of millimeter-and submillimeter-wavelength radiation are becoming more and more widespread in our society. As such, there is a growing need to better understand and quantify both the coupling mechanisms and the impact of this long wavelength energy on biological function. Independent of the health impact of high doses of radio frequency (RF) energy on full organisms, there exists the potential for more subtle effects, which can best be quantified in studies which examine real-time changes in cellular function as RF energy is applied. In this paper we present the first real time examination of millimeter-wave induced changes in cellular activity at absorbed power levels well below the existing safe exposure limits of 1mW/cm^2. Using sensitive patch clamp measurements on pyramidal neurons in cortical slices of neonatal rats, the authors present the first direct evidence of millimeter-wave induced changes in action potential firing rates and membrane porosity. Non-invasive modulation of neuronal activity could prove useful in a variety of health applications from suppression of peripheral neuropathic pain to treatment of central neurological disorders

Millimeter wave-induced changes in membrane properties of leech Retzius neurons

This study evaluated a novel method for modulation of neuronal excitability using non-invasive delivery of millimeter waves. Millimeter waves at 60 GHz and incident power density of 100-600 μW/cm^2 were applied to three intact segmental ganglia of the adult leach, and intracellular neuronal activity was recorded from the Retzius neurons using intracellular glass electrode. Transient dosedependent increase in the plasma membrane permeability was observed. In addition, in one of the examined neurons, a decrease in the neuronal firing rate was also evident. The results provide strong evidence for the feasibility of modulating neuronal excitability using non-invasive delivery of millimeter waves, and will be explored further for applications in basic neuroscience and treatment of neurological disorders

Diagnosis and Treatment of Neurological Disorders by Millimeter-Wave Stimulation

Increasingly, millimeter waves are being employed for telecomm, radar, and imaging applications. To date in the U.S, however, very few investigations on the impact of this radiation on biological systems at the cellular level have been undertaken. In the beginning, to examine the impact of millimeter waves on cellular processes, researchers discovered that cell membrane depolarization may be triggered by low levels of integrated power at these high frequencies. Such a situation could be used to advantage in the direct stimulation of neuronal cells for applications in neuroprosthetics and diagnosing or treating neurological disorders. An experimental system was set up to directly monitor cell response on exposure to continuous-wave, fixed-frequency, millimeter-wave radiation at low and modest power levels (0.1 to 100 safe exposure standards) between 50 and 100 GHz. Two immortalized cell lines derived from lung and neuronal tissue were transfected with green fluorescent protein (GFP) that locates on the inside of the cell membrane lipid bi-layer. Oxonol dye was added to the cell medium. When membrane depolarization occurs, the oxonal bound to the outer wall of the lipid bi-layer can penetrate close to the inner wall where the GFP resides. Under fluorescent excitation (488 nm), the normally green GFP (520 nm) optical signal quenches and gives rise to a red output when the oxonol comes close enough to the GFP to excite a fluorescence resonance energy transfer (FRET) with an output at 620 nm. The presence of a strong FRET signature upon exposures of 30 seconds to 2 minutes at 5-10 milliwatts per square centimeter RF power at 50 GHz, followed by a return to the normal 520-nm GFP signal after a few minutes indicating repolarization of the membrane, indicates that low levels of RF energy may be able to trigger non-destructive membrane depolarization without direct cell contact. Such a mechanism could be used to stimulate neuronal cells in the cortex without the need for invasive electrodes as millimeter waves penetrate skin and bone on the order of 15 mm in depth. Although 50 GHz could not readily penetrate from the outer skull to the center of the cortex, implants on the outer skull or even on the scalp could reach the outer layer of the cerebral cortex where substantial benefit could be realized from such non-contact type excitation

Effects of millimeter wave irradiation and equivalent thermal heating on the activity of individual neurons in the leech ganglion

Many of today's radiofrequency-emitting devices in telecommunication, telemedicine, transportation safety, and security/military applications use the millimeter-wave (MMW) band (30-300 GHz). To evaluate the biological safety and possible applications of this radiofrequency band for neuroscience and neurology, we have investigated the physiological effects of low-intensity 60 GHz electromagnetic irradiation on individual neurons in the leech midbody ganglia. We applied incident power densities of 1, 2, and 4 mW/cm^2 to the whole ganglion for a period of 1 minute, while recording the action potential with a standard sharp-electrode electrophysiology setup. For comparison, the recognized U.S. safe exposure limit is 1 mW/cm^2 for 6 minutes. During the exposure to MMWs and gradual bath heating at a rate of 0.04 ºC/sec (2.4 ºC/min), the ganglionic neurons exhibited similar dose-dependent hyperpolarization of the plasma membrane and decrease in the action potential amplitude. However, narrowing of the action potential half-width during MMW irradiation at 4 mW/cm^2 was 5 times more pronounced, as compared to equivalent bath heating of 0.6 ºC. Even more dramatic difference in the effects of MMW irradiation and bath heating was on the firing rate, which was suppressed at all applied MMW power densities and was increased in a dose-dependent manner during gradual bath heating. The mechanism of enhanced narrowing of action potentials and suppressed firing by MMW irradiation, as compared to gradual bath heating, is hypothesized to involve specific coupling of MMW energy with the neuronal plasma membrane

Compact non-invasive millimeter-wave glucose sensor

The authors describe a compact non-invasive CMOS-circuit-based glucose monitor using millimeter-wave transmission for use on animal and human subjects. Using an earlier device, in vivo measurements were performed through the ear in anesthetized animals and correlated with blood glucose concentration from test strips. In addition, millimeter wave absorption through glucose-containing solutions was measured in specialized liquid transmission cells and is shown to correlate with the animal and separate in vitro data. Design and performance information on the CMOS transceiver are given

Comparison of the effects of millimeter wave irradiation, general bath heating, and localized heating on neuronal activity in the leech ganglion

The use of electrically-induced neuromodulation has grown in importance in the treatment of multiple neurological disorders such as Parkinson’s disease, dystonia, epilepsy, chronic pain, cluster headaches and others. While electrical current can be applied locally, it requires placing stimulation electrodes in direct contact with the neural tissue. Our goal is to develop a method for localized application of electromagnetic energy to the brain without direct tissue contact. Toward this goal, we are experimenting with the wireless transmission of millimeter wave (MMW) energy in the 10-100 GHz frequency range, where penetration and focusing can be traded off to provide non-contact irradiation of the cerebral cortex. Initial experiments have been conducted on freshly-isolated leech ganglia to evaluate the real-time changes in the activity of individual neurons upon exposure to the MMW radiation. The initial results indicate that low-intensity MMWs can partially suppress the neuronal activity. This is in contrast to general bath heating, which had an excitatory effect on the neuronal activity. Further studies are underway to determine the changes in the state of the membrane channels that might be responsible for the observed neuromodulatory effects. © (2013) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only

Bioelectronic medicines: a research roadmap

Realizing the vision of a new class of medicines based on modulating the electrical signalling patterns of the peripheral nervous system needs a firm research foundation. Here, an interdisciplinary community puts forward a research roadmap for the next 5 years