Electromagnetic method for the noninvasive analysis of cell membrane physiology and pharmacology

• US 4,240,027 A
• Filed: 08/31/1978
• Issued: 12/16/1980
• Est. Priority Date: 08/31/1978
• Status: Expired due to Term

• Current Assignee: United States Of America As Represented By The Secretary Of The Army (Government of the United States of America)
• Original Assignee: The United States Of America As Represented By The Secretary Of The Army
• Inventors: Larsen, Lawrence E., Jacobi, John H.
• Primary Examiner(s): Karlsen, Ernest F.
• Application Number:
  US05/938,625
• Time in Patent Office: 838 Days
• Field of Search: 324/57 R, 324/60 R, 324/60 C, 324/61 R, 324/61 P, 128/734
• US Class Current: 324/638
• CPC Class Codes: G01N 33/48735 Investigating suspensions of cells, e.g. measuring microbe concentration by chemical means C12Q1/04; colony counters C12M1/34; concentration of particle suspensions in general G01N15/06

Abstract

A method for electromagnetic analysis of cellular or cell ghost physiology and pharmacology without disrupting the physcial integrity of the cell membrane is described. The method utilizes the technique of multifrequency automatic network analysis and signal processing to derive complex permittivities from the error corrected complex reflection coefficient of cell containing samples at each measured frequency. Complex permittivity at each frequency is then related to the dispersion in dielectric conductivity (a term which includes ohmic and non-ohmic losses) thereby measuring the ion permeability barrier and transport functions of the cell membrane and ion distribution inside of and outside of the cell membrane. The method measures the complex reflection coefficient of a capacitive termination containing a cellular sample as high frequencies are applied. Meaningful data can be developed in the range of frequencies of from 100 KHz to 100 MHz depending upon the exact nature of the cells and the automatic network analyzer used.

Claims

1. A method for noninvasive analysis of cell membrane physiology and pharmacology by measurement of the reflection coefficient with electromagnetic energy in the high frequency band applied to cellular suspensions in order to evaluate the selective permeability thereof comprising the steps of subjecting a sample of cell suspension to two port automatic network analysis step-wise over a plurality of preselected frequencies in the high frequency band and measuring the reflection coefficient thereof for each of the plurality of preselected frequencies and calculating the complex permittivity at each of the plurality of preselected frequencies to determine contrast between the introcellular and extracellular spaces based upon the dispersion of complex permittivity.

2. The method of claim 1 which employs a capacitive termination of a test set for a first of said ports for said analysis;

and measuring the complex reflection coefficient of said cell suspension in said capacitive termination in response to a plurality of known frequency inputs not to exceed a range of 100 MHz to 500 MHz.

3. The method of claim 2 wherein said analysis is carried out at 1 MHz steps throughout the range of from 1 to 40 MHz.

4. The method of claim 3 further comprising providing a capacitive termination for said analysis consisting of a coaxial chamber fabricated from a female type N bulkhead connector having a center conductor and a shell therearound wherein said cell suspension is disposed between the outer surface of the center conductor and the inner surface of the surrounding shell, and correcting said measured coefficient for the polarization impedance attributable to said conductors.

5. The method of claim 4 wherein said sample is a cell suspension selected from the group consisting of red blood cells and fibroblasts.

6. The method of claim 4 wherein said sample is suspended in a physiological medium.