Sauer's non-linear voltage division.

The non-linearity of the electrode-tissue interface impedance gives rise to harmonics and thus degrades the accuracy of impedance measurements. Also, electrodes are often driven into the non-linear range of their polarisation impedance. This is particularly true in clinical applications. Techniques to correct for electrode effects are usually based on linear electrode impedance data. However, these data can be very different from the non-linear values needed. Non-linear electrode data suggested a model based on simple assumptions. It is useful in predicting the frequency dependence of non-linear effects from linear properties. Sauer's treatment is a first attempt to provide a more general and rigorous basis for modelling the non-linear state. The paper reports Sauer's treatment of the non-linear case and points out its limitations. The paper considers Sauer's treatment of a series arrangement of two impedances. The tissue impedance is represented by a linear voltage-current characteristic. The interface impedance is represented by a Volterra expansion. The response of this network to periodic signals is calculated up to the second-order term of the series expansion. The resultant, time-dependent current is found to contain a DC term (rectification), as well as frequency-dependent terms. Sauer's treatment assumes a voltage clamp across the impedances and neglects higher-order terms in the series expansion. As a consequence, it fails adequately to represent some experimentally observed phenomena. It is therefore suggested that Sauer's expressions for the voltage divider should be combined with the non-linear treatments previously published by the co-authors. Although Sauer's work on the non-linear voltage divider was originally applied to the study of the non-linear behaviour of the electrode-electrolyte interface and biological tissues, it is stressed, however, that the work is applicable to a wide range of research areas.

Bioelectromagnetics, Carl Durney, and dosimetry: some historical remarks.

The contributions of Carl Durney to dosimetry have decisively advanced the bioelectromagnetics field and led to significant revisions of relevant health standards. Three items come to mind while studying his work: 1. The work of Carl Durney and his colleagues in dosimetry has advanced the bioelectromagnetics field most significantly whereas more abundant work of a biomedical nature has had less impact. More biophysics work is desirable. 2. The rationale for the specific absorption rate as a basis of health standards needs further elaboration. The need for scaling animal results is stressed. 3. Dosimetry at the cellular level (microdosimetry) is essential if one cares to discuss direct field interactions at the cellular and macromolecular level. Carl Durney's recognition of this need is stated. Carl Durney's wide range of productive interests is indicated by several tables. They summarize his many contributions to electrical engineering, education, bioelectromagnetic dosimetry, hyperthermia, NMR, and field-induced biophysical phenomena at the molecular and cellular level. His scientific work is summarized, including how his interest changed with time. His scientific accomplishment and productive interaction with students, colleagues, and society sets an example to be admired.

Detection by 4-parameter microscopic imaging and increase of rare mononuclear blood leukocyte types expressing the Fc gamma RIII receptor (CD16) for immunoglobulin G in human sporadic amyotrophic lateral sclerosis (ALS).

By using quantitative multiparameter microscopic imaging we demonstrate concentration of two peripheral mononuclear blood leukocyte types expressing the Fc gamma RIII receptor for immunoglobulin G in a clinical subgroup of amyotrophic lateral sclerosis (ALS, n = 9) showing bulbar palsy (ALSBP) and/or predominant involvement of the upper motor neuron (ALSC). Triple fluorescence staining and overlay with phase contrast images (4 parameters) reveals that cell type 1 co-expresses Fc gamma RIII (CD16), CD8 and CD57 surface antigens (ALSC 50 +/- 33.6 cells/microliters, P = 0.0012; ALSBP 16.5 +/- 32.4, P = 0.029). This cell type is not observed in healthy individuals (n = 8) and is only insignificantly increased (P > 0.05) in neurological disease controls (stroke, n = 3, 2.1 +/- 3.7; polymyositis, n = 6, 1.5 +/- 4.0 cells/microliters) and in ALS cases with peripheral symptoms (ALSP n = 12: 7.6 +/- 8.7). Cell type 2 co-expresses Fc gamma RIII (CD16) and CD8, but is negative for CD57 (ALSC 60.1 +/- 19.3; ALSBP 24.2 +/- 28.0 cells/microliters). These findings are consistent with previous reports on IgG isotype changes and immune-cell invasion of the motor system in ALS.

Modelling of the dielectric properties of normal and irradiated skin.

We have shown that irradiation changes the dielectric properties of human skin at radiofrequencies. Both the dielectric constant and the conductivity of the irradiated skin decrease, especially at low frequencies. The experimental data were analysed using two bioelectric models. Relevant dielectric parameters were determined by curve fitting. The dielectric relaxation of the radiation-induced acute or late reaction of the skin occurred at higher frequencies than with normal or non-irradiated skin, while the static conductivity and static dielectric constant of the irradiated skin decreased. We conclude that bioelectric modelling provides a useful tool in the evaluation of cellular changes in irradiated skin.

Harmonic distortion caused by electrode polarisation.

Steady-state measurements of the electrical properties of electrodes immersed in physiological saline were taken with small- and large-amplitude sinusoidal voltages (30 m V-1 V) in the frequency range 0.2 mHz-2 Hz. Impedance magnitude and phase, and the first four Fourier series coefficients of the polarised current were measured. The dependence of the polarisation admittance on input current intensity was modelled with the linear relationship proposed by Schwan. This model predicts harmonics in the non-linear range for AC overpotentials up to several hundred millivolts. Observed values deviated from theoretical values. Reasons for such deviations are discussed. The study of harmonic distortion appears to be a useful tool to monitor and predict the non-linear behaviour of the interface and other dielectric phenomena.

History of medical and biological ultrasound at the University of Pennsylvania.

We briefly review my early contacts with bioacoustics and the bioacoustic work at the University of Pennsylvania that took place from the early 1950s to 1975. It was carried out with E. L. Carstensen, K. Li, A. Smith, H. Pauly, J. Reid, P. Edmonds and many students. The emphasis was first on basic biophysical studies. The work with E. Carstensen and H. Pauly was primarily concerned with the mechanism causing the high absorption typical for tissues and cell suspensions. Macromolecular content was shown to be largely responsible for the absorption. Practical applications concerned the relative merits of electromagnetic and ultrasonic diathermy techniques. P. Edmonds extended the range of macromolecular studies to 100 MHz and initiated work on the attenuation in lung tissues. After J. Reid came to Pennsylvania, the development of echocardiography took place.

Mechanisms responsible for electrical properties of tissues and cell suspensions.

The electrical properties of tissues and cell suspensions are most unusual. They change with frequency in three distinct steps and their dielectric constants reach enormous values at low frequencies. We shall concentrate on the 'linear' properties as observed with applied fields less than 1 V/cm. The linear properties of interest include the dielectric constant epsilon and conductivity kappa. Extensive measurements have been carried out over a broad frequency range extending from less than 1 Hz to many GHz. Observed frequency changes of these properties obey causality, i.e., the Kramers-Kronig relationships which relate changes of dielectric constants with conductivity changes. A number of mechanisms have been identified which explain the observed data. These mechanisms reflect the various compartments of the biological material. These include membranes and their properties, biological macromolecules and fluid compartments inside and outside membranes. We summarize the mechanisms which contribute to the total frequency response.

Linear and nonlinear electrode polarization and biological materials.

Electrode polarization is a major nuisance while determining dielectric properties of cell and particle suspensions and tissues, particularly at low frequencies. Understanding of these interfacial phenomena and appropriate modelling are essential in order to correct for its distortion of the dielectric properties of the sample of interest. I survey the following topics, concentrating on contributions from our laboratory: Linear properties of electrode polarization and relevant models. Effects of electrode polarization on sample impedance. Effects of sample on polarization impedance. Techniques of correction. Extension of linear to nonlinear models Harmonics generated in the nonlinear range.

Early history of bioelectromagnetics.

The early history of bioelectromagnetics is reviewed as I experienced it. The period of time chosen extends from my joining the Institute for Physical Foundations of Medicine in Frankfurt in 1937 to the early 1970s, when I retired from the chair of my department at the University of Pennsylvania. Several themes emerge from these recollections. First, clinical and biological work led almost immediately to a heated controversy about the role of athermal vs. thermal effects; this issue has never been settled to the satisfaction of most. Second, good quantitative work on electrical properties and dosimetry began early, well before World War II; its impact on future developments was significant.

Electrorotation and levitation of cells and colloidal particles.

We review dielectrophoretic forces on cells and colloidal particles, emphasizing their use for manipulating and characterizing the electrical properties of suspended particles. Compared with dielectric spectroscopy, these methods offer a measure of independence from electrode artifacts and mixture theory. On the assumption that the particles can be modeled as uniform dielectric objects with effective dielectric properties, a simple theory can be developed for the frequency variation in the field-induced forces. For particles exhibiting counterion polarization, dielectrophoretic forces differ considerably from predictions of this theory at low frequencies, apparently because of double layer phenomena.

Cellular membrane potentials induced by alternating fields.

Membrane potentials induced by external alternating fields are usually derived assuming that the membrane is insulating, that the cell has no surface conductance, and that the potentials are everywhere solutions of the Laplace equation. This traditional approach is reexamined taking into account membrane conductance, surface admittance, and space charge effects. We find that whenever the conductivity of the medium outside the cell is low, large corrections are needed. Thus, in most of the cases where cells are manipulated by external fields (pore formation, cell fusion, cell rotation, dielectrophoresis) the field applied to the cell membrane is significantly reduced, sometimes practically abolished. This could have a strong bearing on present theories of pore formation, and of the influence of weak electric fields on membranes.

Organizational development of biomedical engineering.

The evolution of biomedical engineering is traced, beginning with its roots in electrophysiology about 200 years ago. Significant research and professional developments during the 1940s, '50s, and '60s are sketched. Five major events that contributed to these developments are discussed. They are the split between biophysics and bioengineering (1957), S. Talbot's BME study grant (1958-60), the impact of the National Institutes of Health (since 1958), the IEEE ;BME-crisis' (1967/68), and the IEEE Bioengineering Society's founding (1968) and its BME view as an extension of physiology.

Biomedical engineering: University of Pennsylvania-from research laboratory to a leader in educational institutions for bioengineering.

The evolution of the Electromedical Laboratory of the Moore School of Electrical Engineering at the University of Pennsylvania into a biomedical engineering department is summarized. Administrative and educational details for the period when the author served as head and chair (1952-1973) are related.

Nonlinear phenomenon of interfacial polarization immittance of a Pt electrode.

Description of a computerized, automated method to measure the interfacial polarization immittance of a Pt electrode in nonlinear range is presented. The classical three-electrode setup is used for measurements in conjunction with a special purpose software implemented on a Unix computer using C language. A collection of data at very low frequencies (below 2 Hz) and at high input intensities with various dc biases imposed on the input are presented to show the behavior of the interface in nonlinear range. The instrument also provides on-line harmonic analysis of the output signal, by calculating the first four Fourier series coefficients, in response to a pure sinusoidal input.

Dielectric properties of tissues and biological materials: a critical review.

We critically review bulk electrical properties of tissues and other biological materials, from DC to 20 GHz, with emphasis on the underlying mechanisms responsible for the properties. We summarize the classical principles behind dielectric relaxation and critically review recent developments in this field. Special topics include a summary of the significant recent advances in theories of counterion polarization effects, dielectric properties of cancer vs. normal tissues, properties of low-water-content tissues, and macroscopic field-coupling considerations. Finally, the dielectric properties of tissues are summarized as empirical correlations with tissue water content in other compositional variables; in addition, a comprehensive table is presented of dielectric properties. The bulk electrical properties of tissues are needed for many bioengineering applications of electric fields or currents, and they provide insight into the basic mechanisms that govern the interaction of electric fields with tissue.

Biological effects of non-ionizing radiations: cellular properties and interactions.

The Lauriston Taylor lectures honor the founder of the National Committee on Radiation Protection and Measurement, soon to be followed by the corresponding international organization. These standard setting bodies had a vast influence on proper recognition of radiation hazards. The 10th Taylor lecture is the first to deal with nonionizing radiations and may be, therefore, of particular interest to the bioengineer. During early history biophysics and bioengineering were primarily concerned with ionizing radiation bioeffects and electrophysiology. The nonionizing part of the radiation field and electrophysiology are closely related. Biomedical observation, biophysical and bioengineering efforts in the nonionizing radiation field are defined and complement each other. Topics concentrate on the relevant biophysical and bioengineering efforts of the author and his colleagues. They include: electrical properties of biological systems; established electrical field interactions (excitation, macromolecular responses and cellular responses); problems of dosimetry (macroscopic and microscopic considerations); conclusions about relative merits of various research approaches.

Alignment of microscopic particles in electric fields and its biological implications.

It is well known that electromagnetic fields cause mechanical forces. If one applies an electrical field to a suspension of microscopic particles, these particles realign themselves along the direction of the field and form pearl-chain-like aggregates. These chains are mostly single stranded but they are frequently multistranded. This phenomenon has been investigated by a number of groups. Here we discuss the dependence of threshold field strength on particle size and frequency. Also, pulsed fields have been thought to be more effective than continuous fields of the same average power in evoking biological effects. Our measurement of the threshold power requirement for the pearl-chain formation indicates that pulsed fields require as much power as continuous fields. The biological significance of pearl-chain formation is briefly discussed.