The electrical properties of tissues and cell
suspensions are most unusu .I. They change with
frequency in three distinct steps and their dielectric
constants reach enormous values at low frequencies.
We concentrate on the “linear” properties observed
with applied fields less than about 1 V/cm. The linear
properties of interest include the dielectric constant E
and conductivity (T. Extensive measurements have been
carried out over a broad frequency range extending
from less than 1 Hz to many GHz. A number of
mechanism 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.
Original Title
ELECTRICAL PROPERTIES OF TISSUES AND CELL SUSPENSIONS:
MECHANISMS AND MODELS
The electrical properties of tissues and cell
suspensions are most unusu .I. They change with
frequency in three distinct steps and their dielectric
constants reach enormous values at low frequencies.
We concentrate on the “linear” properties observed
with applied fields less than about 1 V/cm. The linear
properties of interest include the dielectric constant E
and conductivity (T. Extensive measurements have been
carried out over a broad frequency range extending
from less than 1 Hz to many GHz. A number of
mechanism 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.
The electrical properties of tissues and cell
suspensions are most unusu .I. They change with
frequency in three distinct steps and their dielectric
constants reach enormous values at low frequencies.
We concentrate on the “linear” properties observed
with applied fields less than about 1 V/cm. The linear
properties of interest include the dielectric constant E
and conductivity (T. Extensive measurements have been
carried out over a broad frequency range extending
from less than 1 Hz to many GHz. A number of
mechanism 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.
ELECTRICAL PROPERTIES OF TISSUES AND CELL SUSPENSIONS:
MECHANISMS AND MODELS
H.P. Schwan Bioengineering Department, University of Pennsylvania Philadelphia, PA 19 104 ABSTMX. The electrical properties of tissues and cell suspensions are most unusu .I. They change with frequency in three distinct steps and their dielectric constants reach enormous values at low frequencies. We concentrate on the linear properties observed with applied fields less than about 1 V/cm. The linear properties of interest include the dielectric constant E and conductivity (T. Extensive measurements have been carried out over a broad frequency range extending from less than 1 Hz to many GHz. A number of mechanism 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. INTRODUCTKN The dielectric properties of biological matter and tissues are unusual for several reasons (Fig.1): 1. The electrical properties display at first glance characteristics typical of fractal systems. The frequency dependence of dielectric constant E and conductivity (T can be approximated by a response characterized by a frequency independent phase angle and obeying both the Fricke and Kramers Kronig relationships. 2. More detailed research revealed that changes with frequency occur in three distinct major steps at low, RF and GHz fequencies and termed a. fl and y dispersions. 3. Dielectric constants reach enormous values of millions relative to free space at low frequencies. &DISPERSION. This dispersion usually occurs in the range 0,l - 10 MHz. Its mechanism was first analyzed by Hugo Fricke and K.S Cole [l]. It is caused by the cellular structure of tissues, with poorly conducting membranes separating cytoplasm and extracellular space. It takes time to charge the membranes through the conducting phases in- and outside the cell membranes. The time constant of this process is readily derived from Laplacian potential theory and is determined by cell membrane capacitance, cell radius and the fluid resistivities [2,3]. Refinements and extensions of the theory were developed and applied to a large number of cell suspensions in order to extract from AC bioimpedance measurements cellular parameters such as membrane capacitance and fluid resistivities in- and outside the cell by Carstensen, Hanai and Schwan and their coworkers [2,3]. This effect results from the inhomogeneous structure of tissues and cell suspensions. Such effects are termed Maxwell-Wagner effects since Maxwell treated the DC case and Wagner exctendet it to AC frequencies. Superimposed on the p-dispersion caused by the cell are other effects which contribute to to the tail of the main p-dispersion, including (2-5): a. Relaxation effects caused by proteins and to a lesser extend amino acid residues. b. Smaller Maxwell-Wagner contributions caused by organelles inside the cell, primarily cell nuclei and mitochondria. 1 O8 l o5 IO e 10 i o 6 10 Hz 10 10 CT ( mS / c ml 10 1 Fig.1. Dielectric constant E (decreasing) and conductivity (T (increasing) as function of frequency. 0-7803-2050-6/94 $4.00 01994 IEEE 70a y - DISPERSION. The yeffect was noted for a variety of tissues and protein solutions above 1 GHr [2-51. This effect was not unexpected since water relaxes near 20 GHz and tissues and cells contain much water. A weaker subsidiary dispersion effect (&dispersion) is due to protein bound water [2,4]. Such water appears to display a broad spectrum of dispersions extending from about 100 MHz to some GHz. It probably overlaps with the small contributions due to amino acids and polar subgroups of proteins aforementioned. The quantitative details of the y -dispersions are fairly well understood. It is obvious from the dielectric data that tissue water is identical to normal water except for the small fraction near proteins. a -DISPERSION. The discovery of the a-dispersion came as a great surprise. I noticed it first with muscle tissue in 1948 and then with colloidal suspensions a few years later. A multitude of various mechanism contribute to a-dispersions [5]. The three best established mechanism are: a. The work with colloidal solutions indicated the existence of frequency dependent surface conductances and capacitances, largely caused by the response of the counterion atmosphere existing near the charged cell surface. b. In muscle tissue the existence of the sarcoplasmic reticulum appears to be primarily responsible for the strong dispersion. c. Cell membranes contain channel proteins whose conductance varies with frequency. This is predicted from the Hodgkin-Huxley equations. The understanding of the a-dispersion remains incomplete for several reasons: a. Theories of the counterion atmosphere predict that the dispersion should occur at lower frequencies than observed with many cellular systems. b. Most tissues with high water content display similar low frequency dispersions, including tissues without tubular systems. Furthermore, E Coli suspensions display very high low frequency dielectric constants, quite comparable to those of tissues.Thus the effect can not be solely due to such systems as the tubular system in muscle tissue. c. The channel conductance effects appear to occur at lower frequencies than the observed a-effect. d. Some cells such as erythrocytes display no a-effect while many other including E. Coli display remarkable effects. Clearly, more work needs to be done to sort out the various contributors to the a-response. The table presents the various mechanisms participating in the dielectric response of different biological systems, advancing from simple water to the complex case of cells with internal organelles, proteins and charged membranes. Table. Electrical Dispersions of Biomatter Water and electrolytes Y amino acids 6 + Y proteins P + 6 + Y Biological Macromolecules: nucleic acids a + P + G + y Vesicles, no surface charge II P + Y with " a + P + y Cells with membranes: +fluids free of protein P + Y + protein P + S + Y +surface charge a + P + y +membrane relaxation a + P + y +organelles P + 6 + Y +tubular system a + P + y Cells with membranes, surface charges, organelles, proteins a + P+ G+ y REFERENCES [l ] K.S. Cole, Membranes, Ions and Impul ses. University of California Press, Berkeley and Los Angeles,l968. [2] H.P. Schwan, Electrical properties of tissue and cell suspensions in: Advances in Biological and Medical Physics . Vo1.5 , Editors: J .H.Lawrence and C.A.Tobias. Academic Press, New York, pp. 147-209, 1957. [SI K.R. Foster and H. P. Schwan, Dielectric properties of tissues and biological materials: A critical review, CRC Critical Reviews in Biomedical Engineering 17:1, pp.25-104, 1989. [4] E.H. Grant, R.J . Sheppard and G.P.South, Dielectric behavior of biological molecules in solution. Oxford University Press, Oxford., 1978. [5] H.P. Schwan and S. Takashima, Electrical conduction and dielectric behavior in biological systems, in: Encyclopedia of Applied Physics, Vol. Biophysics and Medical Physics, Editor: G.L. Trigg, VCH publishers, New York and Weinheim,l993. 71a
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