CN-122003204-A - Method and apparatus for measuring electrical impedance and assessing biological condition of tissue samples

CN122003204ACN 122003204 ACN122003204 ACN 122003204ACN-122003204-A

Abstract

The present invention relates generally to the field of biological condition assessment of tissues and tissue samples. In particular, the present invention relates to methods and apparatus for assessing an ex-vivo tissue sample, for example in medical pathology, and in particular to methods and apparatus for characterizing an ex-vivo tissue sample using accurate electrical impedance measurements of the tissue.

Inventors

N. Ascari Lord
LARSEN RENAUD
A. Berntesson
A. Akdis
Y. Mita Village
BORST JOACHIM

Assignees

科学基础有限公司

Dates

Publication Date: 20260508
Application Date: 20240704
Priority Date: 20230818

Claims (8)

1. A medical system for ex vivo tissue sample analysis, comprising: A medical device holder configured to hold a medical device in a fixed position relative to an ex-vivo tissue sample, wherein an electrode array of the medical device abuts the tissue sample at a predetermined pressure; A medical device, further comprising: An impedance measurement unit connected to the electrode array and configured to deliver a current into the tissue sample via electrodes of the electrode array to obtain tissue impedance data of a tissue region of the tissue sample, the tissue impedance data comprising a plurality of impedance values measured in the tissue region, and An electronic computer in communication with the impedance measurement unit to control activation of the electrode array, the electronic computer operating according to a stored program to: Applying a measurement cycle comprising performing a plurality of subsequent measurements at a plurality of predetermined frequencies in a predetermined frequency spectrum, and For each measurement in the measurement cycle, controlling a first electrode of an electrode pair of the electrode array to inject a current into or apply a voltage to the tissue sample, and controlling a second electrode of the electrode pair to measure a resulting current or resulting voltage from the tissue sample.
2. The system of claim 1, wherein the electronic computer operates according to a stored program to apply an evaluation procedure that analyzes a biological condition of the tissue sample based on the measured impedance data of the tissue region and evaluates the obtained impedance value dataset to provide a result indicative of a biological condition state.
3. The system of claim 1 or 2, wherein the medical device comprises a probe for measuring an electrical impedance of tissue of the subject, the device comprising a plurality of electrodes adapted to be in direct contact with the skin sample and connectable to an impedance measurement circuit adapted to apply a voltage and measure a resulting current to determine the impedance signal.
4. A system according to claim 3, wherein the probe comprises switching circuitry for selectively activating pairs of electrodes by connecting at least two electrodes with the impedance measurement circuitry and disconnecting the remaining electrodes from the impedance circuitry, wherein a voltage is applied to the two electrodes and a resulting current is measured between the at least two electrodes.
5. The system of claim 4, wherein the switching circuit is adapted to receive a control signal from the electronic computer, the control signal instructing the switching circuit to activate the electrode pairs according to a predetermined activation scheme, the predetermined activation scheme comprising activating adjacent electrodes in a sequential manner to progressively scan the subject tissue at a first tissue depth to obtain a sequence of impedance signals from a selected tissue depth.
6. A test kit for analysis of an ex-vivo tissue sample includes a medical device holder configured to hold a medical device in a fixed position relative to an ex-vivo tissue sample, wherein an electrode array of the medical device abuts the tissue sample at a predetermined pressure, a medical device further including an impedance measurement unit connected to the electrode array and configured to pass a current into the tissue sample via electrodes of the electrode array to obtain tissue impedance data of a tissue region of the tissue sample, the tissue impedance data including a plurality of impedance values measured in the tissue region, and an electronic computer in communication with the impedance measurement unit to control activation of the electrode array, the electronic computer operating in accordance with a stored program to apply a measurement cycle including performing a plurality of subsequent measurements at a plurality of predetermined frequencies in a predetermined frequency spectrum, and for each measurement in the measurement cycle, to control a first electrode of an electrode pair of the electrode array to inject a current into the tissue sample or to apply a voltage to the tissue sample, and to control a current or a voltage from a second electrode of the electrode pair to the tissue sample.
7. A method for in vitro tissue sample analysis, comprising the steps of: Disposing a medical device in a medical device holder in a fixed position relative to an ex-vivo tissue sample, wherein an electrode array of the medical device abuts the tissue sample at a predetermined pressure; Measuring impedance by passing current through electrodes of the electrode array into the tissue sample to obtain tissue impedance data of a tissue region of the tissue sample, the tissue impedance data comprising a plurality of impedance values measured in the tissue region, and A measurement cycle is applied comprising performing a plurality of subsequent measurements at a plurality of predetermined frequencies in a predetermined frequency spectrum.
8. The method of claim 7, further comprising: An electronic computer is instructed to control activation of the electrode array, the electronic computer operating according to a stored program to apply a measurement cycle including performing a plurality of subsequent measurements at a plurality of predetermined frequencies in a predetermined frequency spectrum, and for each measurement in the measurement cycle, to control a first electrode of an electrode pair of the electrode array to inject a current into or apply a voltage to the tissue sample, and to control a second electrode of the electrode pair to measure a resulting current or resulting voltage from the tissue sample.

Description

Method and apparatus for measuring electrical impedance and assessing biological condition of tissue samples Technical Field The present invention relates generally to the field of biological condition assessment of tissues and tissue samples. In particular, the present invention relates to methods and apparatus for assessing an ex-vivo tissue sample, for example in medical pathology, and in particular to methods and apparatus for characterizing an ex-vivo tissue sample using accurate electrical impedance measurements of the tissue. Background Epithelial tissue is composed of tightly bound layers of specialized cells, the main function of which is to form a physical and chemical barrier between the body and the external environment. The epithelial barrier protects the internal tissues from environmental stresses by minimizing water loss and preventing the ingress of pathogens, contaminants, toxins and allergens through the skin or mucosa. Recent genome-wide association studies have shown that epithelial barrier function plays a key role in a variety of allergic diseases. Barrier defects have been reported in atopic dermatitis, asthma, chronic sinusitis, allergic rhinitis, eosinophilic esophagitis, and colitis. The defect is the starting point for chronic inflammation and allergen sensitization, and allows tissue damaging factors to enter deep tissues, activating immune and inflammatory responses. The skin has two barrier structures, stratum corneum and tight junctions (Tight Junction, TJ). The stratum corneum is the outermost layer of the epidermis, and is composed of terminally differentiated keratinocytes (called keratinocytes), which form a densely packed and extensively crosslinked lipid-protein matrix. Filaggrin, papilin and endocapelin play a key role in skin barrier function by interacting with keratin intermediate filaments. The most important component of the epithelial barrier is represented by TJ, which closes the cell bypass gap between adjacent epithelial cells at the apical side of the mucosa and at the level of the granular layer in the skin. TJ is responsible for epithelial permeability by controlling the cell bypass flux of ions and larger molecules and physically separates two distinct compartments. TJ is essential for proper epithelial cell differentiation and function and is deeply involved in signal transduction as well as epithelial proliferation and differentiation. They form large complexes in the cell membrane, comprising three major types of transmembrane proteins, claudin family, tightly linked related MARVEL (MAL and related proteins for vesicle transport and membrane ligation) protein family, single transmembrane proteins (e.g., immunoglobulin-like protein ligation adhesion molecules (Junction Adhesion Molecule, JAM) and coxsackievirus and adenovirus receptors (Coxsackie and Adenovirus Receptor, CAR)). Within the cell, transmembrane proteins bind to a variety of scaffold proteins, such as the zonula occludens family of proteins (Zonula Occludens, ZO), which in turn are linked to the actin cytoskeleton. Historically, epithelial barriers have been evaluated by in vitro measurements of Trans-epithelial resistance (Trans-EPITHELIAL ELECTRICAL RESISTANCE, TEER), TEER representing the impedance of the epithelium to the passage of steady current. For this purpose, the epithelial cells were cultured in a Transwell culture plate to the gas-liquid interface (Air Liquid Interface, ALI). The confluence of the cell integrity determines a sharp rise in TEER, indicating low ion flux and tight epithelial barriers, whereas disruption of the junction complex results in a decrease in TEER. Furthermore, TEER measurements correlated well negatively with fluorescein-labeled dextran permeability, which has been demonstrated in ALI culture of different tissues. Less invasive methods are available in vivo for assessing epithelial barrier function. One of these is to quantify the transepidermal water Loss of the skin through the stratum corneum (Trans-EPIDERMAL WATER Loss, TEWL). Although TEWL increases proportionally with the extent of damage, it is also affected by environmental factors such as humidity, temperature, season and skin moisture content. Other commonly used non-invasive methods include stratum corneum hydration, colorimetry, skin surface pH and sebum determination. They provide information about different properties and/or conditions of the skin, but do not directly measure the barrier function. Impairment of epithelial barrier function is associated with a variety of skin and mucosal allergies, metabolic and autoimmune disorders. 1-5 Since the 60 s of the 20 th century, the prevalence of these diseases has increased dramatically in the western world and continues to increase in developing countries. 6-8 The epithelial barrier hypothesis has recently been proposed to explain the cause of such growth. 6,9,10 Like many other diseases, allergic diseases result from complex gene-environment in