Patch clampThe patch clamp technique is a laboratory technique in electrophysiology used to study ionic currents in individual isolated living cells, tissue sections, or patches of cell membrane. The technique is especially useful in the study of excitable cells such as neurons, cardiomyocytes, muscle fibers, and pancreatic beta cells, and can also be applied to the study of bacterial ion channels in specially prepared giant spheroplasts. Patch clamping can be performed using the voltage clamp technique.
Ion channelIon 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 ions across the cell membrane, controlling the flow of ions across secretory and epithelial cells, and regulating cell volume. Ion channels are present in the membranes of all cells. Ion channels are one of the two classes of ionophoric proteins, the other being ion transporters.
Voltage-gated ion channelVoltage-gated ion channels are a class of transmembrane proteins that form ion channels that are activated by changes in the electrical membrane potential near the channel. The membrane potential alters the conformation of the channel proteins, regulating their opening and closing. Cell membranes are generally impermeable to ions, thus they must diffuse through the membrane through transmembrane protein channels. They have a crucial role in excitable cells such as neuronal and muscle tissues, allowing a rapid and co-ordinated depolarization in response to triggering voltage change.
Patch-sequencingPatch-sequencing (patch-seq) is a method designed for tackling specific problems involved in characterizing neurons. As neural tissues are one of the most transcriptomically diverse populations of cells, classifying neurons into cell types in order to understand the circuits they form is a major challenge for neuroscientists. Combining classical classification methods with single cell RNA-sequencing post-hoc has proved to be difficult and slow.
Potassium channelPotassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of cell functions. Potassium channels function to conduct potassium ions down their electrochemical gradient, doing so both rapidly (up to the diffusion rate of K+ ions in bulk water) and selectively (excluding, most notably, sodium despite the sub-angstrom difference in ionic radius).
ElectrophysiologyElectrophysiology (from Greek ἥλεκτ, ēlektron, "amber" [see the etymology of "electron"]; φύσις, physis, "nature, origin"; and -λογία, -logia) is the branch of physiology that studies the electrical properties of biological cells and tissues. It involves measurements of voltage changes or electric current or manipulations on a wide variety of scales from single ion channel proteins to whole organs like the heart. In neuroscience, it includes measurements of the electrical activity of neurons, and, in particular, action potential activity.
MicrofluidicsMicrofluidics refers to a system that manipulates a small amount of fluids ((10−9 to 10−18 liters) using small channels with sizes ten to hundreds micrometres. It is a multidisciplinary field that involves molecular analysis, biodefence, molecular biology, and microelectronics. It has practical applications in the design of systems that process low volumes of fluids to achieve multiplexing, automation, and high-throughput screening.
Ligand-gated ion channelLigand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl− to pass through the membrane in response to the binding of a chemical messenger (i.e. a ligand), such as a neurotransmitter. When a presynaptic neuron is excited, it releases a neurotransmitter from vesicles into the synaptic cleft. The neurotransmitter then binds to receptors located on the postsynaptic neuron.
Voltage clampThe voltage clamp is an experimental method used by electrophysiologists to measure the ion currents through the membranes of excitable cells, such as neurons, while holding the membrane voltage at a set level. A basic voltage clamp will iteratively measure the membrane potential, and then change the membrane potential (voltage) to a desired value by adding the necessary current. This "clamps" the cell membrane at a desired constant voltage, allowing the voltage clamp to record what currents are delivered.
MEMSMEMS (Microelectromechanical systems) is the technology of microscopic devices incorporating both electronic and moving parts. MEMS are made up of components between 1 and 100 micrometres in size (i.e., 0.001 to 0.1 mm), and MEMS devices generally range in size from 20 micrometres to a millimetre (i.e., 0.02 to 1.0 mm), although components arranged in arrays (e.g., digital micromirror devices) can be more than 1000 mm2.
Semiconductor device fabricationSemiconductor device fabrication is the process used to manufacture semiconductor devices, typically integrated circuits (ICs) such as computer processors, microcontrollers, and memory chips (such as NAND flash and DRAM) that are present in everyday electrical and electronic devices. It is a multiple-step photolithographic and physio-chemical process (with steps such as thermal oxidation, thin-film deposition, ion-implantation, etching) during which electronic circuits are gradually created on a wafer, typically made of pure single-crystal semiconducting material.
Hyperpolarization (biology)Hyperpolarization is a change in a cell's membrane potential that makes it more negative. It is the opposite of a depolarization. It inhibits action potentials by increasing the stimulus required to move the membrane potential to the action potential threshold. Hyperpolarization is often caused by efflux of K+ (a cation) through K+ channels, or influx of Cl– (an anion) through Cl– channels. On the other hand, influx of cations, e.g. Na+ through Na+ channels or Ca2+ through Ca2+ channels, inhibits hyperpolarization.
Integrated circuitAn integrated circuit or monolithic integrated circuit (also referred to as an IC, a chip, or a microchip) is a set of electronic circuits on one small flat piece (or "chip") of semiconductor material, usually silicon. Large numbers of miniaturized transistors and other electronic components are integrated together on the chip. This results in circuits that are orders of magnitude smaller, faster, and less expensive than those constructed of discrete components, allowing a large transistor count.
Drug discoveryIn the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which new candidate medications are discovered. Historically, drugs were discovered by identifying the active ingredient from traditional remedies or by serendipitous discovery, as with penicillin. More recently, chemical libraries of synthetic small molecules, natural products or extracts were screened in intact cells or whole organisms to identify substances that had a desirable therapeutic effect in a process known as classical pharmacology.
Paper-based microfluidicsPaper-based microfluidics are microfluidic devices that consist of a series of hydrophilic cellulose or nitrocellulose fibers that transport fluid from an inlet through the porous medium to a desired outlet or region of the device, by means of capillary action. This technology builds on the conventional lateral flow test which is capable of detecting many infectious agents and chemical contaminants. The main advantage of this is that it is largely a passively controlled device unlike more complex microfluidic devices.
Semiconductor fabrication plantIn the microelectronics industry, a semiconductor fabrication plant (commonly called a fab; sometimes foundry) is a factory for semiconductor device fabrication. Fabs require many expensive devices to function. Estimates put the cost of building a new fab over one billion U.S. dollars with values as high as 3–4billionnotbeinguncommon.TSMCinvested9.3 billion in its Fab15 300 mm wafer manufacturing facility in Taiwan. The same company estimations suggest that their future fab might cost $20 billion. Lab-on-a-chipA lab-on-a-chip (LOC) is a device that integrates one or several laboratory functions on a single integrated circuit (commonly called a "chip") of only millimeters to a few square centimeters to achieve automation and high-throughput screening. LOCs can handle extremely small fluid volumes down to less than pico-liters. Lab-on-a-chip devices are a subset of microelectromechanical systems (MEMS) devices and sometimes called "micro total analysis systems" (μTAS). LOCs may use microfluidics, the physics, manipulation and study of minute amounts of fluids.
65 nm processThe 65 nm process is an advanced lithographic node used in volume CMOS (MOSFET) semiconductor fabrication. Printed linewidths (i.e. transistor gate lengths) can reach as low as 25 nm on a nominally 65 nm process, while the pitch between two lines may be greater than 130 nm. For comparison, cellular ribosomes are about 20 nm end-to-end. A crystal of bulk silicon has a lattice constant of 0.543 nm, so such transistors are on the order of 100 atoms across. By September 2007, Intel, AMD, IBM, UMC and Chartered were also producing 65 nm chips.
Drug designDrug design, often referred to as rational drug design or simply rational design, is the inventive process of finding new medications based on the knowledge of a biological target. The drug is most commonly an organic small molecule that activates or inhibits the function of a biomolecule such as a protein, which in turn results in a therapeutic benefit to the patient. In the most basic sense, drug design involves the design of molecules that are complementary in shape and charge to the biomolecular target with which they interact and therefore will bind to it.
Fragment-based lead discoveryFragment-based lead discovery (FBLD) also known as fragment-based drug discovery (FBDD) is a method used for finding lead compounds as part of the drug discovery process. Fragments are small organic molecules which are small in size and low in molecular weight. It is based on identifying small chemical fragments, which may bind only weakly to the biological target, and then growing them or combining them to produce a lead with a higher affinity. FBLD can be compared with high-throughput screening (HTS).
