Bulk Reagent Dispenser
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A bulk reagent dispenser (BRD) is a type of commercially available laboratory equipment that dispenses liquid reagents in an
automated Automation describes a wide range of technologies that reduce human intervention in processes, mainly by predetermining decision criteria, subprocess relationships, and related actions, as well as embodying those predeterminations in machine ...
fashion into
microplate A microplate, also known as a microtiter plate, microwell plate or multiwell, is a flat plate with multiple "wells" used as small test tubes. The microplate has become a standard tool in analytical research and clinical diagnostic testing lab ...
s, multiwell plates, or microplate-like reservoirs, and specifically have the ability to transfer liquid from a "bulk" (i.e. >1L) source reservoir, but still dispense a programmable but relatively small volume of liquid, i.e. 10-500 μL. They are often used in drug discovery or
pharmaceutical Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the ...
laboratories. They are distinguished from semi-automated or manual (hand-operated) equipment like
pipettes A pipette (sometimes spelled as pipet) is a type of laboratory tool commonly used in chemistry and biology to transport a measured volume of liquid, often as a media dispenser. Pipettes come in several designs for various purposes with differing ...
, as well as from automated laboratory equipment that dispenses from relatively small source reservoirs (~10-500 μL) such as acoustic liquid handlers or
liquid handling robot A liquid handling robot is used to automate workflows in life science laboratories. It is a robot that dispenses a selected quantity of reagent, samples or other liquid to a designated container. Introduction Liquid handling plays a pivot ...
s.


History

The first bulk reagent dispensers were the Titertek Autodrop and
Dynatech Dynatech Corporation, originally Microtech Research Corporation, was an American technology corporation originally based in Burlington, Massachusetts. The company owned a wide variety of manufacturing subsidiaries across multiple industries, inclu ...
Dynadrop MR that were first commercialized in the early 1980s & were used in immunology applications, such as diagnostic experiments to determine viral titer or
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay is a solid-phase type of enzyme immunoassay (EIA) to detect the presence of ...
assays. Modern examples include the Thermo Multidrop Combi series, or the
Agilent Agilent Technologies, Inc. is an American global company headquartered in Santa Clara, California, that provides instruments, software, services, and consumables for laboratories. Agilent was established in 1999 as a spin-off from Hewlett-Packar ...
(formerly BioTek) MultiFlo and MicroFill series.


Principles and capabilities


Pumps

Bulk reagent dispensers use the following technologies to transfer liquid: *
Peristaltic pump A peristaltic pump, also commonly known as a roller pump, is a type of positive displacement pump used for pumping a variety of fluids. The fluid is contained in a flexible tube fitted inside a circular pump casing. Most peristaltic pumps work th ...
s, which have the advantage of having a liquid path that can be entirely defined (i.e. silicone tubing), and thus may be able to be used with non-aequeous reagents like certain organic solvents, but have the disadvantage that the pulsatile pressure will often cause
aerosolization Aerosolization is the process or act of converting some physical substance into the form of particles small and light enough to be carried on the air i.e. into an aerosol. Aerosolization refers to a process of intentionally oxidatively converting a ...
& large droplet formation of the dispensed liquid, and generally transfers using a peristaltic pump have a higher CV than alternatives. *
Syringe pump A syringe driver, also known as a syringe pump, is a small infusion pump, used to gradually administer small amounts of fluid (with or without medication) to a patient or for use in chemical and biomedical research. Some syringe drivers can both ...
s, which use a
syringe A syringe is a simple reciprocating pump consisting of a plunger (though in modern syringes, it is actually a piston) that fits tightly within a cylindrical tube called a barrel. The plunger can be linearly pulled and pushed along the inside ...
&
check valve A check valve, non-return valve, reflux valve, retention valve, foot valve, or one-way valve is a valve that normally allows fluid (liquid or gas) to flow through it in only one direction. Check valves are two-port valves, meaning they have ...
s to deliver liquid with a more constant pressure and lower CV than peristaltic pumps.


Channels & tips

Bulk reagent dispensers also have channels and tips for dispensing liquid. Based on the 8-row or 12-column configuration of standard
microplate A microplate, also known as a microtiter plate, microwell plate or multiwell, is a flat plate with multiple "wells" used as small test tubes. The microplate has become a standard tool in analytical research and clinical diagnostic testing lab ...
s, all modern bulk reagent dispensers currently have either: * 8-channel dispense tips (horizontal traversal to fill a microplate) or * 12-channel dispense tips (vertical traversal to fill a microplate)


Manifolds

Beyond the style and number of independent pumps, channels, and tips, BRDs also might use a
manifold In mathematics, a manifold is a topological space that locally resembles Euclidean space near each point. More precisely, an n-dimensional manifold, or ''n-manifold'' for short, is a topological space with the property that each point has a N ...
to distribute liquid: * with a manifold (1-inlet per multiple dispense tips, common with syringe pump BRDs), or * no manifold (one-inlet per each-channel, and one-channel per each tip, common with peristaltic pump BRDs). If either the fluid inlet or dispense tips become partially or fully clogged, the performance of the BRD will become degraded in distinct and potentially subtle ways depending on if a manifold was used or not.


Movement axes

Bulk reagent dispensers require moving the dispense tips across the target wells, such that a relatively small number of pumps and tips can fill a large number of microplate wells. But even still, there are a few varieties: * 2-axis movement using an X-Z gantry. If using a 2-axis BRD, it can only fill
microplate A microplate, also known as a microtiter plate, microwell plate or multiwell, is a flat plate with multiple "wells" used as small test tubes. The microplate has become a standard tool in analytical research and clinical diagnostic testing lab ...
s or multiwell plates with a well-spacing that is equal to or greater than the spacing of the dispense tips. For example, a BRD with 8-channel tips is meant to fill 96-well plates, but it could also fill a 24-well multiwell plate, or a "single well" plate (i.e. a reservoir). * 3-axis movement using an X-Y-Z gantry. If using a 3-axis BRD, it can fill microplates or multiwell plates with a well-spacing that is equal to, greater than, or less than the spacing of the dispense tips. For example, a BRD with 8-channel tips is meant to fill 96-well plates, but could fill a 384-well plate by moving the tips (or plate) in the Y axis. It is worth mentioning, that for reasons of space & presumably mechanical design constraints, the degrees of freedom of movement for a BRD are typically spread across both the tips and the microplate. I.e. the microplate is moved in the X dimension, while the tips move in the Z (and Y) dimension(s).


References


External links


Bulk Reagent Dispensers: Ubiquitous liquid handling tool for microplate filling
An informative 2010 review on the use of bulk reagent dispensers in the pharmaceutical industry {{Laboratory equipment Laboratory equipment