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Electrophysiology (from
Greek Greek may refer to: Greece Anything of, from, or related to Greece, a country in Southern Europe: *Greeks, an ethnic group. *Greek language, a branch of the Indo-European language family. **Proto-Greek language, the assumed last common ancestor ...
, ''ēlektron'', "amber" etymology_of_"electron".html" ;"title="Electron#Etymology">etymology of "electron"">Electron#Etymology">etymology of "electron" , ''physis'', "nature, origin"; and , ''
-logia ''-logy'' is a suffix in the English language, used with words originally adapted from Ancient Greek ending in ('). The earliest English examples were anglicizations of the French '' -logie'', which was in turn inherited from the Latin '' -logi ...
'') is the branch of
physiology Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical ...
that studies the electrical properties of biological
cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...
s and tissues. It involves measurements of
voltage Voltage, also known as electric pressure, electric tension, or (electric) potential difference, is the difference in electric potential between two points. In a static electric field, it corresponds to the work needed per unit of charge to ...
changes or electric current or manipulations on a wide variety of scales from single ion channel
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s to whole organs like the
heart The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide to t ...
. In
neuroscience Neuroscience is the scientific study of the nervous system (the brain, spinal cord, and peripheral nervous system), its functions and disorders. It is a multidisciplinary science that combines physiology, anatomy, molecular biology, developme ...
, it includes measurements of the electrical activity of neurons, and, in particular,
action potential An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...
activity. Recordings of large-scale electric signals from the
nervous system In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes ...
, such as electroencephalography, may also be referred to as electrophysiological recordings. They are useful for
electrodiagnosis Electrodiagnosis (EDX) is a method of medical diagnosis that obtains information about diseases by passively recording the electrical activity of body parts (that is, their natural electrophysiology) or by measuring their response to external elect ...
and
monitoring Monitoring may refer to: Science and technology Biology and healthcare * Monitoring (medicine), the observation of a disease, condition or one or several medical parameters over time * Baby monitoring * Biomonitoring, of toxic chemical compounds, ...
.


Definition and scope


Classical electrophysiological techniques


Principle and mechanisms

Electrophysiology is the branch of physiology that pertains broadly to the flow of ions (
ion current Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of i ...
) in biological tissues and, in particular, to the electrical recording techniques that enable the measurement of this flow. Classical electrophysiology techniques involve placing
electrodes An electrode is an electrical conductor used to make contact with a nonmetallic part of a circuit (e.g. a semiconductor, an electrolyte, a vacuum or air). Electrodes are essential parts of batteries that can consist of a variety of materials dep ...
into various preparations of biological tissue. The principal types of electrodes are: # simple solid conductors, such as discs and needles (singles or arrays, often insulated except for the tip), # tracings on printed circuit boards or flexible polymers, also insulated except for the tip, and # hollow tubes filled with an electrolyte, such as glass pipettes filled with potassium chloride solution or another electrolyte solution. The principal preparations include: # living organisms (exampl
in insects
, # excised tissue (acute or cultured), # dissociated cells from excised tissue (acute or cultured), # artificially grown cells or tissues, or # hybrids of the above. Neuronal electrophysiology is the study of electrical properties of biological cells and tissues within the nervous system. With neuronal electrophysiology doctors and specialists can determine how neuronal disorders happen, by looking at the individual's brain activity. Activity such as which portions of the brain light up during any situations encountered. If an electrode is small enough (micrometers) in diameter, then the
electrophysiologist Electrophysiology (from Greek , ''ēlektron'', "amber" etymology of "electron"">Electron#Etymology">etymology of "electron" , ''physis'', "nature, origin"; and , ''-logia'') is the branch of physiology that studies the electrical properties of bi ...
may choose to insert the tip into a single cell. Such a configuration allows direct observation an
intracellular recording
of the
intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
electrical activity of a single cell. However, this invasive setup reduces the life of the cell and causes a leak of substances across the cell membrane. Intracellular activity may also be observed using a specially formed (hollow) glass pipette containing an electrolyte. In this technique, the microscopic pipette tip is pressed against the cell membrane, to which it tightly adheres by an interaction between glass and lipids of the cell membrane. The electrolyte within the pipette may be brought into fluid continuity with the cytoplasm by delivering a pulse of negative pressure to the pipette in order to rupture the small patch of membrane encircled by the pipette rim ( whole-cell recording). Alternatively, ionic continuity may be established by "perforating" the patch by allowing exogenous pore-forming agent within the electrolyte to insert themselves into the membrane patch ( perforated patch recording). Finally, the patch may be left intact ( patch recording). The electrophysiologist may choose not to insert the tip into a single cell. Instead, the electrode tip may be left in continuity with the extracellular space. If the tip is small enough, such a configuration may allow indirect observation and recording of
action potential An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...
s from a single cell, termed
single-unit recording In neuroscience, single-unit recordings provide a method of measuring the electro-physiological responses of a single neuron using a microelectrode system. When a neuron generates an action potential, the signal propagates down the neuron as a cu ...
. Depending on the preparation and precise placement, an extracellular configuration may pick up the activity of several nearby cells simultaneously, termed multi-unit recording. As electrode size increases, the resolving power decreases. Larger electrodes are sensitive only to the net activity of many cells, termed
local field potentials Local field potentials (LFP) are transient electrical signals generated in nervous and other tissues by the summed and synchronous electrical activity of the individual cells (e.g. neurons) in that tissue. LFP are "extracellular" signals, meaning ...
. Still larger electrodes, such as uninsulated needles and surface electrodes used by clinical and surgical neurophysiologists, are sensitive only to certain types of synchronous activity within populations of cells numbering in the millions. Other classical electrophysiological techniques include single channel recording and amperometry.


Electrographic modalities by body part

Electrophysiological recording in general is sometimes called electrography (from '' electro-'' + ''
-graphy The English suffix -graphy means a "field of study" or related to "writing" a book, and is an anglicization of the French ''-graphie'' inherited from the Latin ''-graphia'', which is a transliterated direct borrowing from Greek. Arts * Cartogr ...
'', "electrical recording"), with the record thus produced being an electrogram. However, the word ''electrography'' has other
senses A sense is a biological system used by an organism for sensation, the process of gathering information about the world through the detection of stimuli. (For example, in the human body, the brain which is part of the central nervous system rec ...
(including
electrophotography Xerography is a dry photocopying technique. Originally called electrophotography, it was renamed xerography—from the roots el, ξηρός, label=none ''xeros'', meaning "dry" and -γραφία ''-graphia'', meaning "writing"—to emphasize ...
), and the specific types of electrophysiological recording are usually called by specific names, constructed on the pattern of ''electro-'' + combining_form.html"_;"title="classical_compound.html"_;"title="ody_part_classical_compound">combining_form">classical_compound.html"_;"title="ody_part_classical_compound">combining_form+_''-graphy''_(abbreviation_ExG)._Relatedly,_the_word_''electrogram''_(not_being_needed_for_those_other_senses_ A_sense_is_a_biological_system_used_by_an_organism_for_sensation,_the_process_of_gathering_information_about_the_world_through_the_detection_of_stimuli._(For_example,_in_the_human_body,_the_brain_which_is_part_of_the_central_nervous_system_rec_...
)_often_carries_the_specific_meaning_of_intracardiac_electrogram,_which_is_like_an_electrocardiogram_but_with_some_invasive_leads_(inside_the_heart)_rather_than_only_noninvasive_leads_(on_the_skin)._Electrophysiological_recording_for_clinical_medical_diagnosis.html" "title="classical_compound">combining_form.html" ;"title="classical_compound.html" ;"title="ody part classical compound">combining form">classical_compound.html" ;"title="ody part classical compound">combining form+ ''-graphy'' (abbreviation ExG). Relatedly, the word ''electrogram'' (not being needed for those other
senses A sense is a biological system used by an organism for sensation, the process of gathering information about the world through the detection of stimuli. (For example, in the human body, the brain which is part of the central nervous system rec ...
) often carries the specific meaning of intracardiac electrogram, which is like an electrocardiogram but with some invasive leads (inside the heart) rather than only noninvasive leads (on the skin). Electrophysiological recording for clinical medical diagnosis">diagnostic Diagnosis is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in many different disciplines, with variations in the use of logic, analytics, and experience, to determine " cause and effect". In systems engin ...
 purposes is included within the category of electrodiagnostic testing. The various "ExG" modes are as follows:


Optical electrophysiological techniques

Optical electrophysiological techniques were created by scientists and engineers to overcome one of the main limitations of classical techniques. Classical techniques allow observation of electrical activity at approximately a single point within a volume of tissue. Classical techniques singularize a distributed phenomenon. Interest in the spatial distribution of bioelectric activity prompted development of molecules capable of emitting light in response to their electrical or chemical environment. Examples are voltage sensitive dyes and fluorescing proteins. After introducing one or more such compounds into tissue via perfusion, injection or gene expression, the 1 or 2-dimensional distribution of electrical activity may be observed and recorded.


Intracellular recording

Intracellular recording involves measuring voltage and/or current across the membrane of a cell. To make an intracellular recording, the tip of a fine (sharp) microelectrode must be inserted inside the cell, so that the membrane potential can be measured. Typically, the resting membrane potential of a healthy cell will be -60 to -80 mV, and during an action potential the membrane potential might reach +40 mV. In 1963,
Alan Lloyd Hodgkin Sir Alan Lloyd Hodgkin (5 February 1914 – 20 December 1998) was an English physiologist and biophysicist who shared the 1963 Nobel Prize in Physiology or Medicine with Andrew Huxley and John Eccles. Early life and education Hodgkin was ...
and
Andrew Fielding Huxley Sir Andrew Fielding Huxley (22 November 191730 May 2012) was an English physiologist and biophysicist. He was born into the prominent Huxley family. After leaving Westminster School in central London, he went to Trinity College, Cambridge on ...
won the Nobel Prize in Physiology or Medicine for their contribution to understanding the mechanisms underlying the generation of action potentials in neurons. Their experiments involved intracellular recordings from the giant axon of Atlantic squid (''Loligo pealei''), and were among the first applications of the "voltage clamp" technique. Today, most microelectrodes used for intracellular recording are glass micropipettes, with a tip diameter of < 1 micrometre, and a resistance of several megohms. The micropipettes are filled with a solution that has a similar ionic composition to the intracellular fluid of the cell. A chlorided silver wire inserted into the pipet connects the electrolyte electrically to the amplifier and signal processing circuit. The voltage measured by the electrode is compared to the voltage of a reference electrode, usually a silver chloride-coated silver wire in contact with the extracellular fluid around the cell. In general, the smaller the electrode tip, the higher its
electrical resistance The electrical resistance of an object is a measure of its opposition to the flow of electric current. Its reciprocal quantity is , measuring the ease with which an electric current passes. Electrical resistance shares some conceptual paralle ...
, so an electrode is a compromise between size (small enough to penetrate a single cell with minimum damage to the cell) and resistance (low enough so that small neuronal signals can be discerned from thermal noise in the electrode tip).


Voltage clamp

The voltage clamp technique allows an experimenter to "clamp" the cell potential at a chosen value. This makes it possible to measure how much ''ionic current'' crosses a cell's membrane at any given voltage. This is important because many of the ion channels in the membrane of a neuron are voltage-gated ion channels, which open only when the membrane voltage is within a certain range. Voltage clamp measurements of current are made possible by the near-simultaneous digital subtraction of transient capacitive currents that pass as the recording electrode and cell membrane are charged to alter the cell's potential.


Current clamp

The current clamp technique records the membrane potential by injecting current into a cell through the recording electrode. Unlike in the voltage clamp mode, where the membrane potential is held at a level determined by the experimenter, in "current clamp" mode the membrane potential is free to vary, and the amplifier records whatever voltage the cell generates on its own or as a result of stimulation. This technique is used to study how a cell responds when electric current enters a cell; this is important for instance for understanding how neurons respond to neurotransmitters that act by opening membrane ion channels. Most current-clamp amplifiers provide little or no amplification of the voltage changes recorded from the cell. The "amplifier" is actually an
electrometer An electrometer is an electrical instrument for measuring electric charge or electrical potential difference. There are many different types, ranging from historical handmade mechanical instruments to high-precision electronic devices. Modern ...
, sometimes referred to as a "unity gain amplifier"; its main purpose is to reduce the electrical load on the small signals (in the mV range) produced by cells so that they can be accurately recorded by low- impedance electronics. The amplifier increases the current behind the signal while decreasing the resistance over which that current passes. Consider this example based on Ohm's law: A voltage of 10 mV is generated by passing 10 nanoamperes of current across 1 MΩ of resistance. The electrometer changes this "high impedance signal" to a "low impedance signal" by using a
voltage follower A buffer amplifier (sometimes simply called a buffer) is one that provides electrical impedance transformation from one circuit to another, with the aim of preventing the signal source from being affected by whatever currents (or voltages, for a cu ...
circuit. A voltage follower reads the voltage on the input (caused by a small current through a big resistor). It then instructs a parallel circuit that has a large current source behind it (the electrical mains) and adjusts the resistance of that parallel circuit to give the same output voltage, but across a lower resistance.


Patch-clamp recording

This technique was developed by Erwin Neher and
Bert Sakmann Bert Sakmann (; born 12 June 1942) is a German cell physiologist. He shared the Nobel Prize in Physiology or Medicine with Erwin Neher in 1991 for their work on "the function of single ion channels in cells," and the invention of the patch cl ...
who received the Nobel Prize in 1991. Conventional intracellular recording involves impaling a cell with a fine electrode; patch-clamp recording takes a different approach. A patch-clamp microelectrode is a micropipette with a relatively large tip diameter. The microelectrode is placed next to a cell, and gentle suction is applied through the microelectrode to draw a piece of the cell membrane (the 'patch') into the microelectrode tip; the glass tip forms a high resistance 'seal' with the cell membrane. This configuration is the "cell-attached" mode, and it can be used for studying the activity of the ion channels that are present in the patch of membrane. If more suction is now applied, the small patch of membrane in the electrode tip can be displaced, leaving the electrode sealed to the rest of the cell. This "whole-cell" mode allows very stable intracellular recording. A disadvantage (compared to conventional intracellular recording with sharp electrodes) is that the intracellular fluid of the cell mixes with the solution inside the recording electrode, and so some important components of the intracellular fluid can be diluted. A variant of this technique, the "perforated patch" technique, tries to minimize these problems. Instead of applying suction to displace the membrane patch from the electrode tip, it is also possible to make small holes on the patch with pore-forming agents so that large molecules such as proteins can stay inside the cell and ions can pass through the holes freely. Also the patch of membrane can be pulled away from the rest of the cell. This approach enables the membrane properties of the patch to be analyzed pharmacologically. Patch-clamp may also be combined with RNA sequencing in a technique known as patch-seq by extracting the cellular contents following recording in order to characterize the electrophysiological properties relationship to gene expression and cell-type.


Sharp electrode recording

In situations where one wants to record the potential inside the cell membrane with minimal effect on the ionic constitution of the intracellular fluid a sharp electrode can be used. These micropipettes (electrodes) are again like those for patch clamp pulled from glass capillaries, but the pore is much smaller so that there is very little ion exchange between the intracellular fluid and the electrolyte in the pipette. The electrical resistance of the micropipette electrode is reduced by filling with 2-4M KCl, rather than a salt concentration which mimics the intracellular ionic concentrations as used in patch clamping. Often the tip of the electrode is filled with various kinds of dyes like Lucifer yellow to fill the cells recorded from, for later confirmation of their morphology under a microscope. The dyes are injected by applying a positive or negative, DC or pulsed voltage to the electrodes depending on the polarity of the dye.


Extracellular recording


Single-unit recording

An electrode introduced into the brain of a living animal will detect electrical activity that is generated by the neurons adjacent to the electrode tip. If the electrode is a microelectrode, with a tip size of about 1 micrometre, the electrode will usually detect the activity of at most one neuron. Recording in this way is in general called "single-unit" recording. The action potentials recorded are very much like the action potentials that are recorded intracellularly, but the signals are very much smaller (typically about 1 mV). Most recordings of the activity of single neurons in anesthetized and conscious animals are made in this way. Recordings of single neurons in living animals have provided important insights into how the brain processes information. For example,
David Hubel David Hunter Hubel (February 27, 1926 – September 22, 2013) was a Canadian American neurophysiologist noted for his studies of the structure and function of the visual cortex. He was co-recipient with Torsten Wiesel of the 1981 Nobel Priz ...
and
Torsten Wiesel Torsten Nils Wiesel (born 3 June 1924) is a Swedish neurophysiologist. With David H. Hubel, he received the 1981 Nobel Prize in Physiology or Medicine, for their discoveries concerning information processing in the visual system; the prize was ...
recorded the activity of single neurons in the primary
visual cortex The visual cortex of the brain is the area of the cerebral cortex that processes visual information. It is located in the occipital lobe. Sensory input originating from the eyes travels through the lateral geniculate nucleus in the thalamus and ...
of the anesthetized cat, and showed how single neurons in this area respond to very specific features of a visual stimulus. Hubel and Wiesel were awarded the Nobel Prize in Physiology or Medicine in 1981.


Multi-unit recording

If the electrode tip is slightly larger, then the electrode might record the activity generated by several neurons. This type of recording is often called "multi-unit recording", and is often used in conscious animals to record changes in the activity in a discrete brain area during normal activity. Recordings from one or more such electrodes that are closely spaced can be used to identify the number of cells around it as well as which of the spikes come from which cell. This process is called spike sorting and is suitable in areas where there are identified types of cells with well defined spike characteristics. If the electrode tip is bigger still, in general the activity of individual neurons cannot be distinguished but the electrode will still be able to record a field potential generated by the activity of many cells.


Field potentials

Extracellular field potentials are local current sinks or sources that are generated by the collective activity of many cells. Usually, a field potential is generated by the simultaneous activation of many neurons by synaptic transmission. The diagram to the right shows hippocampal synaptic field potentials. At the right, the lower trace shows a negative wave that corresponds to a current sink caused by positive charges entering cells through postsynaptic
glutamate receptor Glutamate receptors are synaptic and non synaptic receptors located primarily on the membranes of neuronal and glial cells. Glutamate (the conjugate base of glutamic acid) is abundant in the human body, but particularly in the nervous system ...
s, while the upper trace shows a positive wave that is generated by the current that leaves the cell (at the cell body) to complete the circuit. For more information, see local field potential.


Amperometry

Amperometry uses a carbon electrode to record changes in the chemical composition of the oxidized components of a biological solution. Oxidation and reduction is accomplished by changing the voltage at the active surface of the recording electrode in a process known as "scanning". Because certain brain chemicals lose or gain electrons at characteristic voltages, individual species can be identified. Amperometry has been used for studying exocytosis in the nervous and endocrine systems. Many monoamine
neurotransmitters A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neurot ...
; e.g.,
norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad' ...
(noradrenalin), dopamine, and serotonin (5-HT) are oxidizable. The method can also be used with cells that do not secrete oxidizable neurotransmitters by "loading" them with 5-HT or dopamine.


Planar patch clamp

Planar patch clamp is a novel method developed for high throughput electrophysiology. Instead of positioning a pipette on an adherent cell, cell suspension is pipetted on a
chip Chromatin immunoprecipitation (ChIP) is a type of immunoprecipitation experimental technique used to investigate the interaction between proteins and DNA in the cell. It aims to determine whether specific proteins are associated with specific genom ...
containing a microstructured aperture. A single cell is then positioned on the hole by suction and a tight connection (Gigaseal) is formed. The planar geometry offers a variety of advantages compared to the classical experiment: *It allows for integration of
microfluidics Microfluidics refers to the behavior, precise control, and manipulation of fluids that are geometrically constrained to a small scale (typically sub-millimeter) at which surface forces dominate volumetric forces. It is a multidisciplinary field th ...
, which enables automatic compound application for ion channel screening. *The system is accessible for optical or scanning probe techniques. * Perfusion of the
intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
side can be performed. File:patch pipette model.jpg, Schematic drawing of the classical patch clamp configuration. The patch pipette is moved to the cell using a micromanipulator under optical control. Relative movements between the pipette and the cell have to be avoided in order to keep the cell-pipette connection intact. File:patch pipette.jpg, Scanning electron microscope image of a patch pipette. File:planar patch model.jpg, In planar patch configuration, the cell is positioned by suction. Relative movements between cell and aperture can then be excluded after sealing. An antivibration table is not necessary. File:planar patch chip.jpg, Scanning electron microscope image of a planar patch clamp chip. Both the pipette and the chip are made from
borosilicate Borosilicate glass is a type of glass with silica and boron trioxide as the main glass-forming constituents. Borosilicate glasses are known for having very low coefficients of thermal expansion (≈3 × 10−6 K−1 at 20 °C), ma ...
glass.


Other methods


Solid-supported membrane (SSM)-based

With this electrophysiological approach, proteo
liposome A liposome is a small artificial Vesicle (biology and chemistry), vesicle, spherical in shape, having at least one lipid bilayer. Due to their hydrophobicity and/or hydrophilicity, biocompatibility, particle size and many other properties, lipo ...
s, membrane
vesicle Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry) In cell biology, a vesicle is a structure within or outside a cell, consisting of liquid or cytoplasm enclosed by a lipid bilayer. Vesicles form nat ...
s, or membrane fragments containing the channel or transporter of interest are adsorbed to a lipid monolayer painted over a functionalized electrode. This electrode consists of a glass support, a chromium layer, a
gold Gold is a chemical element with the symbol Au (from la, aurum) and atomic number 79. This makes it one of the higher atomic number elements that occur naturally. It is a bright, slightly orange-yellow, dense, soft, malleable, and ductile me ...
layer, and an octadecyl mercaptane monolayer. Because the painted membrane is supported by the electrode, it is called a solid-supported membrane. It is important to note that mechanical perturbations, which usually destroy a biological lipid membrane, do not influence the life-time of an SSM. The
capacitive A capacitor is a device that stores electrical energy in an electric field by virtue of accumulating electric charges on two close surfaces insulated from each other. It is a passive electronic component with two terminals. The effect of a c ...
electrode (composed of the SSM and the absorbed vesicles) is so mechanically stable that solutions may be rapidly exchanged at its surface. This property allows the application of rapid substrate/ligand concentration jumps to investigate the electrogenic activity of the protein of interest, measured via capacitive coupling between the vesicles and the electrode.


Bioelectric recognition assay (BERA)

The bioelectric recognition assay (BERA) is a novel method for determination of various chemical and biological molecules by measuring changes in the membrane potential of cells immobilized in a gel matrix. Apart from the increased stability of the electrode-cell interface, immobilization preserves the viability and physiological functions of the cells. BERA is used primarily in biosensor applications in order to assay analytes that can interact with the immobilized cells by changing the cell membrane potential. In this way, when a positive sample is added to the sensor, a characteristic, "signature-like" change in electrical potential occurs. BERA is the core technology behind the recently launched pan-European FOODSCAN project, about pesticide and food risk assessment in Europe. BERA has been used for the detection of human viruses (
hepatitis B Hepatitis B is an infectious disease caused by the '' Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. ...
and C viruses and
herpes Herpes simplex is a viral infection caused by the herpes simplex virus. Infections are categorized based on the part of the body infected. Oral herpes involves the face or mouth. It may result in small blisters in groups often called cold ...
viruses), veterinary disease agents (
foot and mouth disease Foot-and-mouth disease (FMD) or hoof-and-mouth disease (HMD) is an infectious and sometimes fatal viral disease that affects cloven-hoofed animals, including domestic and wild bovids. The virus causes a high fever lasting two to six days, follow ...
virus, prions, and blue tongue virus), and plant viruses (tobacco and cucumber viruses) in a specific, rapid (1–2 minutes), reproducible, and cost-efficient fashion. The method has also been used for the detection of environmental toxins, such as pesticides and
mycotoxin A mycotoxin (from the Greek μύκης , "fungus" and τοξίνη , "toxin") is a toxic secondary metabolite produced by organisms of kingdom Fungi and is capable of causing disease and death in both humans and other animals. The term 'mycotoxin' ...
s in food, and
2,4,6-trichloroanisole 2,4,6-Trichloroanisole (TCA) is a chemical compound that is a chlorinated derivative of anisole. TCA is a fungal metabolite of 2,4,6-trichlorophenol, which is used as a fungicide. It can be found in minute traces on packaging materials stored in ...
in cork and wine, as well as the determination of very low concentrations of the
superoxide In chemistry, a superoxide is a compound that contains the superoxide ion, which has the chemical formula . The systematic name of the anion is dioxide(1−). The reactive oxygen ion superoxide is particularly important as the product of t ...
anion in clinical samples. A BERA sensor has two parts: *The consumable biorecognition elements *The electronic read-out device with embedded
artificial intelligence Artificial intelligence (AI) is intelligence—perceiving, synthesizing, and inferring information—demonstrated by machines, as opposed to intelligence displayed by animals and humans. Example tasks in which this is done include speech r ...
. A recent advance is the development of a technique called molecular identification through membrane engineering (MIME). This technique allows for building cells with defined specificity for virtually any molecule of interest, by embedding thousands of artificial receptors into the cell membrane.


Computational electrophysiology

While not strictly constituting an experimental measurement, methods have been developed to examine the conductive properties of proteins and biomembranes '' in silico''. These are mainly
molecular dynamics Molecular dynamics (MD) is a computer simulation method for analyzing the physical movements of atoms and molecules. The atoms and molecules are allowed to interact for a fixed period of time, giving a view of the dynamic "evolution" of t ...
simulations in which a model system like a
lipid bilayer The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many vir ...
is subjected to an externally applied voltage. Studies using these setups have been able to study dynamical phenomena like
electroporation Electroporation, or electropermeabilization, is a microbiology technique in which an electrical field is applied to cells in order to increase the permeability of the cell membrane, allowing chemicals, drugs, electrode arrays or DNA to be introd ...
of membranes and ion translocation by channels. The benefit of such methods is the high level of detail of the active conduction mechanism, given by the inherently high resolution and data density that atomistic simulation affords. There are significant drawbacks, given by the uncertainty of the legitimacy of the model and the computational cost of modeling systems that are large enough and over sufficient timescales to be considered reproducing the macroscopic properties of the systems themselves. While atomistic simulations may access timescales close to, or into the microsecond domain, this is still several orders of magnitude lower than even the resolution of experimental methods such as patch-clamping.


Clinical electrophysiology

Clinical electrophysiology is the study of how electrophysiological principles and technologies can be applied to human health. For example, clinical cardiac electrophysiology is the study of the electrical properties which govern heart rhythm and activity. Cardiac electrophysiology can be used to observe and treat disorders such as arrhythmia (irregular heartbeat). For example, a doctor may insert a catheter containing an electrode into the heart to record the heart muscle's electrical activity. Another example of clinical electrophysiology is
clinical neurophysiology Clinical neurophysiology is a medical specialty that studies the central and peripheral nervous systems through the recording of bioelectrical activity, whether spontaneous or stimulated. It encompasses both research regarding the pathophysiology ...
. In this medical specialty, doctors measure the electrical properties of the
brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...
,
spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the sp ...
, and
nerves A nerve is an enclosed, cable-like bundle of nerve fibers (called axons) in the peripheral nervous system. A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the e ...
. Scientists such as
Duchenne de Boulogne Guillaume-Benjamin-Amand Duchenne (de Boulogne) (September 17, 1806 in Boulogne-sur-Mer – September 15, 1875 in Paris) was a French neurologist who revived Galvani's research and greatly advanced the science of electrophysiology. The era of mo ...
(1806–1875) and Nathaniel A. Buchwald (1924–2006) are considered to have greatly advanced the field of
neurophysiology Neurophysiology is a branch of physiology and neuroscience that studies nervous system function rather than nervous system architecture. This area aids in the diagnosis and monitoring of neurological diseases. Historically, it has been dominated b ...
, enabling its clinical applications.


Clinical reporting guidelines

Minimum Information (MI) standards or reporting guidelines specify the minimum amount of
meta data Metadata is "data that provides information about other data", but not the content of the data, such as the text of a message or the image itself. There are many distinct types of metadata, including: * Descriptive metadata – the descriptive ...
(information) and data required to meet a specific aim or aims in a clinical study. The "Minimum Information about a Neuroscience investigation" (MINI) family of reporting guideline documents aims to provide a consistent set of guidelines in order to report an electrophysiology experiment. In practice a MINI module comprises a checklist of information that should be provided (for example about the protocols employed) when a data set is described for publication.


See also


References


External links


Book chapter on Planar Patch Clamp
{{Authority control Ion channels Neuroimaging Neurophysiology Biophysics