Usuário(a):Tanmaru/Testes: diferenças entre revisões

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A 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.[1] 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. However, strictly regarded "lab-on-a-chip" indicates generally the scaling of single or multiple lab processes down to chip-format, whereas "µTAS" is dedicated to the integration of the total sequence of lab processes to perform chemical analysis. The term "lab-on-a-chip" was introduced when it turned out that µTAS technologies were applicable for more than only analysis purposes.


A 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. However, strictly regarded "lab-on-a-chip" indicates generally the scaling of single or multiple lab processes down to chip-format, whereas "µTAS" is dedicated to the integration of the total sequence of lab processes to perform chemical analysis. The term "lab-on-a-chip" was introduced when it turned out that µTAS technologies were applicable for more than only analysis purposes.


== History ==

After the invention of microtechnology (~1954) for realizing integrated semiconductor structures for microelectronic chips, these lithography-based technologies were soon applied in pressure sensor manufacturing (1966) as well. Due to further development of these usually CMOS-compatibility limited processes, a tool box became available to create micrometre or sub-micrometre sized mechanical structures in silicon wafers as well: the micro electro mechanical systems (MEMS) era had started.

Next to pressure sensors, airbag sensors and other mechanically movable structures, fluid handling devices were developed. Examples are: channels (capillary connections), mixers, valves, pumps and dosing devices. The first LOC analysis system was a gas chromatograph, developed in 1979 by S.C. Terry at Stanford University. However, only at the end of the 1980s and beginning of the 1990s did the LOC research start to seriously grow as a few research groups in Europe developed micropumps, flowsensors and the concepts for integrated fluid treatments for analysis systems. These µTAS concepts demonstrated that integration of pre-treatment steps, usually done at lab-scale, could extend the simple sensor functionality towards a complete laboratory analysis, including additional cleaning and separation steps.

A big boost in research and commercial interest came in the mid 1990s, when µTAS technologies turned out to provide interesting tooling for genomics applications, like capillary electrophoresis and DNA microarrays. A big boost in research support also came from the military, especially from DARPA (Defense Advanced Research Projects Agency), for their interest in portable bio/chemical warfare agent detection systems. The added value was not only limited to integration of lab processes for analysis but also the characteristic possibilities of individual components and the application to other, non-analysis, lab processes. Hence the term "lab-on-a-chip" was introduced.

Although the application of LOCs is still novel and modest, a growing interest of companies and applied research groups is observed in different fields such as analysis (e.g. chemical analysis, environmental monitoring, medical diagnostics and cellomics) but also in synthetic chemistry (e.g. rapid screening and microreactors for pharmaceutics). Besides further application developments, research in LOC systems is expected to extend towards downscaling of fluid handling structures as well, by using nanotechnology. Sub-micrometre and nano-sized channels, DNA labyrinths, single cell detection and analysis, and nano-sensors, might become feasible, allowing new ways of interaction with biological species and large molecules. Many books have been written that cover various aspects of these devices, including the fluid transport, system properties, sensing techniques, and bioanalytical applications.

== Chip materials and fabrication technologies ==

The basis for most LOC fabrication processes is photolithography. Initially most processes were in silicon, as these well-developed technologies were directly derived from semiconductor fabrication. Because of demands for e.g. specific optical characteristics, bio- or chemical compatibility, lower production costs and faster prototyping, new processes have been developed such as glass, ceramics and metal etching, deposition and bonding, polydimethylsiloxane (PDMS) processing (e.g., soft lithography), Off-stoichiometry thiol-ene polymers (OSTEmer) processing, thick-film- and stereolithography-based 3D printing as well as fast replication methods via electroplating, injection molding and embossing. The demand for cheap and easy LOC prototyping resulted in a simple methodology for the fabrication of PDMS microfluidic devices: ESCARGOT (Embedded SCAffold RemovinG Open Technology). This technique allows for the creation of microfluidic channels, in a single block of PDMS, via a dissolvable scaffold (made by e.g. 3D printing). Furthermore, the LOC field more and more exceeds the borders between lithography-based microsystem technology, nanotechnology and precision engineering.

== Advantages ==

LOCs may provide advantages, which are specific to their application. Typical advantages are:

:low fluid volumes consumption (less waste, lower reagents costs and less required sample volumes for diagnostics)
:faster analysis and response times due to short diffusion distances, fast heating, high surface to volume ratios, small heat capacities.
:better process control because of a faster response of the system (e.g. thermal control for exothermic chemical reactions)
:compactness of the systems due to integration of much functionality and small volumes
:massive parallelization due to compactness, which allows high-throughput analysis
:lower fabrication costs, allowing cost-effective disposable chips, fabricated in mass production
:part quality may be verified automatically
:safer platform for chemical, radioactive or biological studies because of integration of functionality, smaller fluid volumes and stored energies

== Disadvantages ==

The most prominent disadvantages of labs-on-chip are:

:The micro-manufacturing process required to make them is complex and labor-intensive, requiring both expensive equipment and specialized personnel. It can be overcome by the recent technology advancement on low-cost 3D printing and laser engraving.
:The complex fluidic actuation network requires multiple pumps and connectors, where fine control is difficult. It can be overcome by careful simulation, an intrinsic pump, such as air-bag embed chip, or by using a centrifugal force to :replace the pumping, i.e. centrifugal micro-fluidic biochip.
:Most LOCs are novel proof of concept application that are not yet fully developed for widespread use. More validations are needed before practical employment.
:In the microliter scale that LOCs deal with, surface dependent effects like capillary forces, surface roughness or chemical interactions are more dominant. This can sometimes make replicating lab processes in LOCs quite challenging and more complex than in conventional lab equipment.
:Detection principles may not always scale down in a positive way, leading to low signal-to-noise ratios.

== Global health ==

Lab-on-a-chip technology may soon become an important part of efforts to improve global health, particularly through the development of point-of-care testing devices. In countries with few healthcare resources, infectious diseases that would be treatable in a developed nation are often deadly. In some cases, poor healthcare clinics have the drugs to treat a certain illness but lack the diagnostic tools to identify patients who should receive the drugs. Many researchers believe that LOC technology may be the key to powerful new diagnostic instruments. The goal of these researchers is to create microfluidic chips that will allow healthcare providers in poorly equipped clinics to perform diagnostic tests such as microbiological culture assays, immunoassays and nucleic acid assays with no laboratory support.

=== Global challenges ===

For the chips to be used in areas with limited resources, many challenges must be overcome. In developed nations, the most highly valued traits for diagnostic tools include speed, sensitivity, and specificity; but in countries where the healthcare infrastructure is less well developed, attributes such as ease of use and shelf life must also be considered. The reagents that come with the chip, for example, must be designed so that they remain effective for months even if the chip is not kept in a climate controlled environment. Chip designers must also keep cost, scalability, and recyclability in mind as they choose what materials and fabrication techniques to use.

=== Examples of global LOC application ===

One of the most prominent and well known LOC devices to reach the market is the at home pregnancy test kit, a device that utilizes paper-based microfluidics technology. Another active area of LOC research involves ways to diagnose and manage common infectious diseases caused by bacteria, eg. bacteriuria or virus, eg. influenza. A gold standard for diagnosing bacteriuria (urinary tract infections) is microbial culture. A recent study based on lab-on-a-chip technology, Digital Dipstick, miniaturised microbiological culture into a dipstick format and enabled it to be used at the point-of-care. When it comes to viral infections, HIV infections are a good example. Around 36.9 million people are infected with HIV in the world today and 59% of these people receive anti-retroviral treatment. Only 75% of people living with HIV knew their HIV status. Measuring the number of CD4+ T lymphocytes in a person's blood is an accurate way to determine if a person has HIV and to track the progress of an HIV infection. At the moment, flow cytometry is the gold standard for obtaining CD4 counts, but flow cytometry is a complicated technique that is not available in most developing areas because it requires trained technicians and expensive equipment. Recently such a cytometer was developed for just $5. Another active area of LOC research is for controlled separation and mixing. In such devices it is possible to quickly diagnose and potentially treat diseases. As mentioned above, a big motivation for development of these is that they can potentially be manufactured at very low cost. One more area of research that is being looked into with regards to LOC is with home security. Automated monitoring of volatile organic compounds (VOCs) is a desired functionality for LOC. If this application becomes reliable, these micro-devices could be installed on a global scale and notify homeowners of potentially dangerous compounds.

== Plant sciences ==

Lab-on-a-chip devices could be used to characterize pollen tube guidance in Arabidopsis thaliana. Specifically, plant on a chip is a miniaturized device in which pollen tissues and ovules could be incubated for plant sciences studies.







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== History ==

=== Early years ===

The first monorail prototype was made in Russia in 1820 by Ivan Elmanov. Attempts at creating monorail alternatives to conventional railways have been made since the early part of the 19th century.

The Centennial Monorail was featured at the Centennial Exposition in Philadelphia in 1876.

Around 1879 a "one-rail" system was proposed independently by Haddon and by Stringfellow, which used an inverted "V" rail (and thus shaped like "Λ" in cross-section). It was intended for military use, but was also seen to have civilian use as a "cheap railway."

The Boynton Bicycle Railroad was a steam-powered monorail in Brooklyn on Long Island, New York. It ran on a single load-bearing rail at ground level, but with a wooden overhead stabilising rail engaged by a pair of horizontally opposed wheels. The railway operated for only two years beginning in 1890.

The Hotchkiss Bicycle Railroad was a monorail on which a matching pedal bicycle could be ridden. The first example was built between Smithville and Mount Holly, New Jersey, in 1892. It closed in 1897. Other examples were built in Norfolk from 1895 to 1909, Great Yarmouth, and Blackpool, UK from 1896.

=== 1900s–1950s ===

Early designs used a double-flanged single metal rail alternative to the double rail of conventional railways, both guiding and supporting the monorail car. A surviving suspended version is the oldest still in service system: the Wuppertal monorail in Germany. Also in the early 1900s, Gyro monorails with cars gyroscopically balanced on top of a single rail were tested, but never developed beyond the prototype stage. The Ewing System, used in the Patiala State Monorail Trainways in Punjab, India, relies on a hybrid model with a load-bearing single rail and an external wheel for balance. One of the first systems put into practical use was that of French engineer Charles Lartigue, who built a line between Ballybunion and Listowel in Ireland, opened in 1888 and closed in 1924 (due to damage from Ireland's Civil War). It uses a load-bearing single rail and two lower, external rails for balance, the three carried on triangular supports.

Possibly the first monorail locomotive was a 0-3-0 steam locomotive.

A highspeed monorail using the Lartigue system was proposed in 1901 between Liverpool and Manchester.

In 1910, the Brennan gyroscopic monorail was considered for use to a coal mine in Alaska. In June 1920, the French Patent Office published FR 503782, by Henri Coanda, on a 'Transporteur Aérien' -Air Carrier.

In the northern Mojave desert, the Epsom Salts Monorail was built in 1924. It ran for 28 miles from a connection on the Trona Railway, eastward to harvest epsomite deposits in the Owlshead Mountains. This non-passenger, Lartigue type monorail achieved gradients of up to ten percent. It only operated until June 1926, when the mineral deposits become uneconomic, and was dismantled for scrap in the late 1930s.

The first half of the 20th century saw many further proposed designs that either never left the drawing board or remained short-lived prototypes. One of the first monorails planned in the United States was in New York City in the early 1930s, scrubbed for an elevated train system.

=== 1950s–1980s ===

In the latter half of the 20th century, monorails had settled on using larger beam- or girder-based track, with vehicles supported by one set of wheels and guided by another. In the 1950s, a 40% scale prototype of a system designed for speed of 200 mph (320 km/h) on straight stretches and 90 mph (140 km/h) on curves was built in Germany. There were designs with vehicles supported, suspended or cantilevered from the beams. In the 1950s the ALWEG straddle design emerged, followed by an updated suspended type, the SAFEGE system. Versions of ALWEG's technology are used by the two largest monorail manufacturers, Hitachi Monorail and Bombardier.

In 1956, the first monorail to operate in the US began test operations in Houston, Texas. Disneyland in Anaheim, California, opened the United States' first daily operating monorail system in 1959. Later during this period, additional monorails were installed at Walt Disney World in Florida, Seattle, and in Japan. Monorails were promoted as futuristic technology with exhibition installations and amusement park purchases, as seen by the legacy systems in use today. However, monorails gained little foothold compared to conventional transport systems. In March 1972, Alejandro Goicoechea-Omar had patent DE1755198 published, on a 'Vertebrate Train', build as experimental track in Las Palmas de Gran Canaria, Spain.

Niche private enterprise uses for monorails emerged, with the emergence of air travel and shopping malls, with shuttle-type systems being built.

=== Perceptions of monorail as public transport ===

From 1950 to 1980, the monorail concept may have suffered, as with all public transport systems, from competition with the automobile. At the time, the post-World War II optimism in America was riding high and people were buying automobiles in large numbers due to suburbanization and the Interstate Highway System. Monorails in particular may have suffered from the reluctance of public transit authorities to invest in the perceived high cost of un-proven technology when faced with cheaper mature alternatives. There were also many competing monorail technologies, splitting their case further. One notable example of a public monorail is the AMF Monorail that was used as transportation around the 1964-1965 World's Fair.

This high-cost perception was challenged most notably in 1963 when the ALWEG consortium proposed to finance the construction of a major system in Los Angeles County, California in return for the right of operation. This was turned down by the Los Angeles County Board of Supervisors under pressure from Standard Oil of California and General Motors (which were strong advocates for automobile dependency), and the later subway system faced criticism by famed author Ray Bradbury as it had yet to reach the scale of the proposed monorail.

Several monorails initially conceived as transport systems survive on revenues generated from tourism, benefiting from the unique views offered from the largely elevated installations.

=== Recent history ===

From the 1980s, most monorail mass transit systems are in Japan, with a few exceptions. Tokyo Monorail, is one of the world's busiest, averages 127,000 passengers per day and has served over 1.5 billion passengers since 1964. China recently started development of monorails in the late 2000s, already home to the world's largest and busiest monorail system and has a number of mass transit monorails under construction in several of cities. A Bombardier Innovia Monorail-based system is under construction in Wuhu and several "Cloudrail" systems developed by BYD under construction a number of cities such as Guang'an, Liuzhou, Bengbu and Guilin. Monorails have seen continuing use in niche shuttle markets and amusement parks.

Modern mass transit monorail systems use developments of the ALWEG beam and tire approach, with only two suspended types in large use. Monorail configurations have also been adopted by maglev trains. Since the 2000s, with the rise of traffic congestion and urbanization, there has been a resurgence of interest in the technology for public transport with a number of cities, such as Malta and Istanbul, today investigating monorails as a possible mass transit solution.

In 2004, Chongqing Rail Transit in China has adopted a unique ALWEG-based design with rolling stock that is much wider than most monorails, with capacity comparable to heavy rail. This is because Chongqing is criss-crossed by numerous hills, mountains and rivers, therefore tunneling is not feasible except in some cases (for example, lines 1 and 6) due to the extreme depth involved. Today it is the largest and busiest monorail system in the world. São Paulo, Brazil is building a Bombardier Innovia Monorail system as part of its public transportation network. The 14.9 mile guideway will have 17 stations, 54 monorail trains and a passenger capacity of 40,000 commuters per hour in each direction. Another city installing a Bombardier Innovia Monorail system in an urban centre is Riyadh, Saudi Arabia, for its new King Abdullah Financial District.

=== Types and technical aspects ===

The Wuppertal Schwebebahn, the world's first electric suspended monorail
Modern monorails depend on a large solid beam as the vehicles' running surface. There are a number of competing designs divided into two broad classes, straddle-beam and suspended monorails. The most common type is the straddle-beam, in which the train straddles a steel or reinforced concrete beam 2 to 3 feet (0.6 to 0.9 m) wide. A rubber-tired carriage contacts the beam on the top and both sides for traction and to stabilize the vehicle. The style was popularized by the German company ALWEG. There is also a historical type of suspension monorail developed by German inventors Nicolaus Otto and Eugen Langen in the 1880s. It was built in the twin cities of Barmen and Elberfeld in Wuppertal, Germany, opened in 1901, and is still in operation. The Chiba Urban Monorail is the world's largest suspended network.




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Magnetic immunoassay (MIA) is a type of diagnostic immunoassay using magnetic beads as labels in lieu of conventional enzymes (ELISA), radioisotopes (RIA) or fluorescent moieties (fluorescent immunoassays) to detect a specified analyte. MIA involves the specific binding of an antibody to its antigen, where a magnetic label is conjugated to one element of the pair. The presence of magnetic beads is then detected by a magnetic reader (magnetometer) which measures the magnetic field change induced by the beads. The signal measured by the magnetometer is proportional to the analyte (virus, toxin, bacteria, cardiac marker, etc.) concentration in the initial sample.

Magnetic labels

Magnetic beads are made of nanometric-sized iron oxide particles encapsulated or glued together with polymers. These magnetic beads range from 35 nm up to 4.5 μm. The component magnetic nanoparticles range from 5 to 50 nm and exhibit a unique quality referred to as superparamagnetism in the presence of an externally applied magnetic field. First discovered by Frenchman Louis Néel, Nobel Physics Prize winner in 1970, this superparamagnetic quality has already been used for medical application in Magnetic Resonance Imaging (MRI) and in biological separations, but not yet for labeling in commercial diagnostic applications. Magnetic labels exhibit several features very well adapted for such applications:

* they are not affected by reagent chemistry or photo-bleaching and are therefore stable over time,
* the magnetic background in a biomolecular sample is usually insignificant,
* sample turbidity or staining have no impact on magnetic properties,
* magnetic beads can be manipulated remotely by magnetism.

Detection

Magnetic Immunoassay (MIA) is able to detect select molecules or pathogens through the use of a magnetically tagged antibody. Functioning in a way similar to that of an ELISA or Western Blot, a two-antibody binding process is used to determine concentrations of analytes. MIA uses antibodies that are coating a magnetic bead. These anti-bodies directly bind to the desired pathogen or molecule and the magnetic signal given off the bound beads is read using a magnetometer. The largest benefit this technology provides for immunostaining is that it can be conducted in a liquid medium, where methods such as ELISA or Western Blotting require a stationary medium for the desired target to bind to before the secondary antibody (such as HRP [Horse Radish Peroxidase]) is able to be applied. Since MIA can be conducted in a liquid medium a more accurate measurement of desired molecules can be performed in the model system. Since no isolation must occur to achieve quantifiable results users can monitor activity within a system. Getting a better idea of the behavior of their target.

The manners in which this detection can occur are very numerous. The most basic form of detection is to run a sample through a gravity column that contains a polyethylene matrix with the secondary anti-body. The target compound binds to the antibody contained in the matrix, and any residual substances are washed out using a chosen buffer. The magnetic antibodies are then passed through the same column and after an incubation period, any unbound antibodies are washed out using the same method as before. The reading obtained from the magnetic beads bound to the target which is captured by the antibodies on the membrane is used to quantify the target compound in solution.

Also, because it is so similar in methodology to ELISA or Western Blot the experiments for MIA can be adapted to use the same detection if the researcher wants to quantify their data in a similar manner.

Magnetometers

A simple instrument can detect the presence and measure the total magnetic signal of a sample, however, the challenge of developing an effective MIA is to separate naturally occurring magnetic background (noise) from the weak magnetically labeled target (signal). Various approaches and devices have been employed to achieve a meaningful signal-to-noise ratio (SNR) for bio-sensing applications:

* giant magneto-resistive sensors and spin valves
* piezo-resistive cantilevers
* inductive sensors
* superconducting quantum interference devices (SQUID)
* anisotropic magneto-resistive rings
* and miniature Hall sensors.

But improving SNR often requires a complex instrument to provide repeated scanning and extrapolation through data processing, or precise alignment of target and sensor of miniature and matching size. Beyond this requirement, MIA that exploits the non-linear magnetic properties of magnetic labels can effectively use the intrinsic ability of a magnetic field to pass through plastic, water, nitrocellulose, and other materials, thus allowing for true volumetric measurements in various immunoassay formats. Unlike conventional methods that measure the susceptibility of superparamagnetic materials, a MIA-based on non-linear magnetization eliminates the impact of linear dia- or paramagnetic materials such as sample matrix, consumable plastics and/or nitrocellulose. Although the intrinsic magnetism of these materials is very weak, with typical susceptibility values of –10−5 (dia) or +10−3 (para), when one is investigating very small quantities of superparamagnetic materials, such as nanograms per test, the background signal generated by ancillary materials cannot be ignored. In MIA based on non-linear magnetic properties of magnetic labels the beads are exposed to an alternating magnetic field at two frequencies, f1 and f2. In the presence of non-linear materials such as superparamagnetic labels, a signal can be recorded at combinatorial frequencies, for example, at f = f1 ± 2×f2. This signal is exactly proportional to the amount of magnetic material inside the reading coil.

This technology makes magnetic immunoassay possible in a variety of formats such as:

:conventional lateral flow test by replacing gold labels with magnetic labels
:vertical flow tests allowing for the interrogation of rare analytes (such as bacteria) in large-volume samples
:microfluidic applications and biochip

It was also described for in vivo applications and for multiparametric testing.

Uses

MIA is a versatile technique that can be used for a wide variety of practices.

Currently it has been used to detect viruses in plants to catch pathogens that would normally devastate crops such as Grapevine fanleaf virus, Grapevine fanleaf virus, and Potato virus X. Its adaptations now include portable devices that allow the user to gather sensitive data in the field.

MIA can also be used to monitor therapeutic drugs. A case report of a 53-year-old kidney transplant patient details how the doctors were able to alter the quantities of the therapeutic drug.













COVID-19 rapid antigen tests, also frequently called COVID-19 lateral flow tests, are rapid antigen tests used to detect SARS-COV-2 infection (COVID-19). They are quick to implement with minimal training, offered significant cost advantages, costing a fraction of other forms of COVID-19 testing and give users a result within 5–30 minutes. However, they have a high false negative rate. Rapid antigen tests are used in several countries as part of mass testing or population-wide screening approaches. They are thought to be valuable for identifying individuals who are asymptomatic and could potentially spread the virus to other people, who would otherwise not know they were infected. This differs from other forms of COVID-19 testing, such as PCR, that are generally seen to be a useful test for symptomatic individuals, as they have a higher sensitivity and can more accurately identify cases.


History of COVID-19 rapid test technology development

Rapid tests for COVID-19 emerged from major investment by the United Kingdom's controversial Moonshot program, a £100 billion program to systematically assess, develop and implement new technologies for COVID-19 testing. Rapid tests initially sat within this systematic evaluation pipeline alongside many other putative COVID-19 testing technologies like Lamp, Lampore, point of care PCR, mass spectrometry and sample pooling. However, as evaluations continued, rapid tests emerged as the most successful form of COVID-19 testing within this program to complement existing PCR testing.

International guidance for COVID-19 rapid test technology use and development

The early scientific rationale for the potential utility of rapid tests and global direction for rapid test technology development was boosted by interim guidance from the WHO that flagged the potential benefits. The report noted that rapid tests were much easier to implement, and had cost benefits. The WHO recommended their use in outbreaks, for early identification of cases and to monitor disease trends. Later, and subsequent to a rapidly increasing body of studies, this recommendation was expanded by the European Commission. The European Commission recommended the use of rapid test technology for population-wide screening where the proportion of test positivity is high or very high. By January 2021, the European Commission agreed to strengthen their position, advocating much greater use of rapid tests, noting that "should research prove that rapid antigen tests can be conducted by the testee themselves.... self-testing with or without professional guidance could also be considered."

Initial studies

One of the definitive studies for rapid tests was completed by Public Health England, University of Oxford and University of Manchester and launched by Professor Richard Body and Dr Lennard Lee. The Falcon-C19 study which was launched within three days on September 17. The first patient was recruited at the Manchester City Etihad stadium carpark at a new COVID-19 testing research centre. The study rapidly extended to include 14 community research sites across the United Kingdom. The study closed on October 23, having completed 878 individuals. The study was one of the fastest recruiting UK COVID-19 research studies in the country. The study provided definitive evidence that rapid test devices were able to pick up positive results with high accuracy. A total of 4 rapid tests, including Innova and Orientgene were validated in this study using swab samples from individuals with symptomatic and asymptomatic disease.

Around the release of the interim analysis of this UK study, the US confirmed that 100 million rapid tests would be purchased from Abbott and shipping to across the country to start similar US studies to complement the University of Oxford initiated studies.

Valuation studies across the world

On 2 November, Slovakia became the first country in the world to initiate country-wide mass testing using rapid tests. Five million rapid tests were performed by 60,000 staff who used the SD Biosensor antigen test and performed swabbing on the population. This then led the European Commission to recommend that rapid tests be used as part of population-wide screening. Two research studies published in early 2021, one by professor Martin Kahanec from Central European University and his coauthors and another one by Martin Pavelka from the London School of Hygiene & Tropical Medicine and his team suggest that the effects of the Autumn wave of rapid antigen mass testing in Slovakia helped to suppress the pandemic in the country, although according to the former study the effect of mass testing on the pandemic was temporary and started to dissipate after about two weeks.

The United Kingdom continued their ongoing rapid test development program using the Innova rapid test, with increasing urgency as COVID-19 cases increased across Europe. On the 6th of November, the Prime Minister, Boris Johnson started city-wide screening of Liverpool as part of the accelerated technology evaluation. Further expansion of rapid tests pilots were also launched for many sectors where testing had not been previously available. These included students at Universities who had been particularly hit by outbreaks. This initially started at Durham University who had the infrastructure and expertise to manage the rapid test program, but was expanded the majority of UK Universities and enabled the national evacuation-style plan to get students safely home for Christmas. Rapid tests were also implemented within the National Health Service for staff to reduce possible transmission to patients, local authorities and Care homes to enable visits to visit residents. On the 18th of November, Wales completed the first whole borough testing at a Merthyr Tydfil. At this time, testing was also implemented across schools in the US for students with symptoms and across Portuguese care homes and schools.

Global efforts to step up evaluations of rapid tests were initiated by the World Health Organization (WHO) Emergencies Department who launched a major rapid diagnostic test implementation project on the 10th of November, aided by agreement from the Bill and Melinda Gates Foundation that limited costs for Low and middle-income countries.

Austria started country-wide mass testing on 5 December and ordered seven million tests consisting of the SD Biosensor test and Siemens Clinitest (aka Orientgene).

By the middle of December, there were many studies confirming the efficacy and success of using rapid tests to identify individuals with COVID-19 including studies in the Netherlands, the United Kingdom, and the US. These studies all enabled rapid tests to enter standard national COVID-19 testing strategies. Global piloting of rapid tests was now common place in schools in Canada, travel hubs in Indonesia, and across India.

Concerns about use

Many individuals have raised concerns that the accuracy of rapid tests were not as good as the existing form of COVID-19 testing PCR. Data released from the United Kingdom's City-wide screen in Liverpool illustrated that army operators of the test did obtain the test performance of trained laboratory scientists, following other pilots in India. This caused minor issues within the scientific-psychological community where there was a debate about whether rapid tests might lead to false reassurance and a change in behaviour. However, a shift in thinking about the use of rapid tests was confirmed following a publication from the US. Professor Michael Mina theorised that rapid tests would still be useful as it identified infectious individuals, and potential benefits observed from repeating rapid test and getting a result much quicker than other forms of testing. The United Kingdom's chief clinical medic, Dr Susan Hopkins, also noted that rapid tests provided a means to find “people that...we couldn't otherwise find”.

Noting the ability to identify cases more rapidly, and considering the ensuing escalation in cases in Europe, the European commission met on 11 December and developed a common European framework for “use, validation and mutual recognition of rapid tests”, committing 100 million euros for the purchase of tests from Roche and Abbott. Stella Kyriakides, commissioner for Health and Food Safety said "Rapid antigen tests offer us speed, reliability and quick responses to isolate COVID cases. This is crucial to slow down the spread of the pandemic."

Other individuals have raised concerns about the slow uptake and deployment of rapid tests and potential loss of life that might have occurred as a result. An academic group from Canada noted that half the deaths in care homes in the early part of the pandemic could have been prevented with rapid tests.


Global regulatory approval for use for COVID-19 testing

Following the success of numerous studies across the world to analyse rapid tests from August 2020, rapid tests were approved by regulatory bodies across the world as part of a strategy to use testing as “a new approach to combat the pandemic”. On 16 December, the FDA became the first authority to approve the Abbott rapid test. Subsequent approvals were given for the Ellume COVID-19 home test.

Rapid tests were also approved by Health Canada with their advisor, Professor David Juncter noting “the best rapid tests are highly accurate at detecting contagious individuals“ and Infectious disease specialist Jean Longtin noting "It will allow us to move faster than the virus and find the person's contacts in an hour or two, instead of waiting 24 hours".

The United Kingdom's MHRA confirmed their approval of the Innova rapid test for self-use testing on 23 December. Following the clear global success of this global development of rapid tests, Sir John Bell, Regius professor of medicine at the University of Oxford said “Rapid tests were a central bit of good defence against coronavirus because they were fast, cheap and available for repeat use”.

Rapid tests as a "return to normal"

Spain became the first country to use Rapid tests to facilitate a return-to-normal with Rapid tests being widely available in pharmacies, and a free music concert held in Barcelona for individuals who took a rapid test. A similar approach was taken in Albania to enable music festivals. However, many experts were unsure of this approach believing that “rapid tests are not the solution to restart normal life” but might be used in combination with other vital infection prevention control measures such as wearing appropriate PPE, washing hands regularly and social distancing to allow people to have that vital time with those they love while helping to keep them safer.

New COVID-19 strains

On 22 December 2020, a new more infectious strain of SARS-CoV-2 was identified in the United Kingdom, VOC-202012/01. The strain rapidly spread across the world. With widespread global use of this form of COVID-19 testing, there was a concern that this variant would render rapid testing obsolete. As part of the UK's accelerated technology evaluation of lateral flow, within 24 hours, Public Health England laboratories were able to confirm rapid test in global development were not affected and they could identify the new variant. This was because rapid test generally targets the nucleocapsid protein and not the spike protein. Some strains however, have recently been identified that do affect some rapid test's sensitivity up to 1000-fold. Fortunately, the frequency of these nucleocapsid mutations (specifically D399N) is still relatively low globally at ~0.02%.

Humanitarian uses for rapid tests

In addition to routine community use, rapid tests have also been utilised as part of humanitarian efforts during the pandemic. Following the flooding in Jakarta in Indonesia on 2 December, Rapid tests were made available in flood shelters. Furthermore, following the closure of national borders in Europe following the emergency of the new UK strain just before Christmas, nearly 6,000 lorry drivers were stranded without food, effectively stopping Christmas food deliveries. Rapid tests were deployed by French firefighters within 24 hours at the Channel. Rapid tests enabled lorries to get on the road and complete their deliveries and return to their families for Christmas, demonstrating the potential global utility of having an easily implementable COVID-19 test. Médecins Sans Frontières strongly endorsed the use of rapid tests in lower and middle income countries noting "COVID-19 antigen tests can deliver rapid and actionable results, ensuring timely identification of people infected with the virus at the community level".

America and rapid tests

Having initially invested considerably in rapid test technology development along with the United Kingdom, further evaluation of rapid tests as part of mass testing approaches in the US stalled as a result of the impasse around the $900 billion in COVID-19 relief contained within the 2020 Consolidated Appropriations Act, 2021. The bill was criticised for not specifically ring-fencing investment in rapid tests as a cost-economical and effective form of population-wide testing. Scientists in the US, such as Professor Michael Mina of Harvard University noted that tests were a “very powerful adjunct to everything else that people are already doing” and that "home tests for COVID-19 Could Slash Infection Rate". This view was reinforced by Professor William A. Haseltine also of Harvard in an article in Forbes magazine proposing "rapid, self-administered testing could stem the ever-surging tide of disease and death" and an article by Professor Annie Sparrow of Mount Sinai, New York proposing "Cheap Mass Testing is Vital for Pandemic Victory" in view of "the emergency of the highly contagious and fast-spreading B117 strain in the UK, and a similar strain from South Africa". Nevertheless, rapid home tests for COVID-19 were publicly available to individuals in January 2021 following the earlier FDA approval. These tests were reimbursed by US health insurance for people with covid-19 symptoms, or those who have had close contact with an infected person or with someone showing symptoms. An article in the Washington Post proposed that the maximum benefit of rapid tests in the US might not be realised until "federal government covered testing for asymptomatic people because transmission by those people is such a huge part of the outbreak" as testing these individuals was not covered by health insurance. Following the election of a new president in January 2021, the US began to restart investing in rapid test technology development with the publication of presidential executive orders.

Global market value

Following the widespread use of rapid tests across the world, rapid tests have a market value of $15 billion, however, the market is expected to cease from 2024 due to the vaccination of global population by the end of 2023. In the US, the market for rapid tests was US$3.9 billion with a >20% growth rate in hospitals, clinics, Asia Pacific but also as end-user tests. International market analysts have forecasted that manufacturers of rapid tests will face ongoing increasing demands as more individuals and countries start to use rapid tests to identify individuals with milder symptoms. A number of commentators and scientists from the US had raised concerns whether the global manufacturing network were able to meet global demand and manufacture the hundreds of millions of tests that would be needed for frequent rapid testing.





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Lateral flow tests (LFTs), also known as lateral flow immunochromatographic assays or rapid tests, are simple devices intended to detect the presence of a target substance in a liquid sample without the need for specialized and costly equipment. These tests are widely used in medical diagnostics for home testing, point of care testing, or laboratory use. For instance, the home pregnancy test is an LFT that detects a certain hormone. These tests are simple, economic and generally show results in around five to 30 minutes. Many lab-based applications increase the sensitivity of simple LFTs by employing additional dedicated equipment.

LFTs operate on the same principles as the enzyme-linked immunosorbent assays (ELISA). In essence, these tests run the liquid sample along the surface of a pad with reactive molecules that show a visual positive or negative result. The pads are based on a series of capillary beds, such as pieces of porous paper, microstructured polymer, or sintered polymer. Each of these pads has the capacity to transport fluid (e.g., urine, blood, saliva) spontaneously.

The sample pad acts as a sponge and holds an excess of sample fluid. Once soaked, the fluid flows to the second conjugate pad in which the manufacturer has stored freeze dried bio-active particles called conjugates (see below) in a salt-sugar matrix. The conjugate pad contains all the reagents required for an optimized chemical reaction between the target molecule (e.g., an antigen) and its chemical partner (e.g., antibody) that has been immobilized on the particle's surface. This marks target particles as they pass through the pad and continue across to the test and control lines. The test line shows a signal, often a color as in pregnancy tests. The control line contains affinity ligands which show whether the sample has flowed through and the bio-molecules in the conjugate pad are active. After passing these reaction zones, the fluid enters the final porous material, the wick, that simply acts as a waste container.

LFTs can operate as either competitive or sandwich assays.


Synopsis

Colored particles

In principle, any colored particle can be used, however latex (blue color) or nanometer-sized particles of gold (red color) are most commonly used. The gold particles are red in color due to localized surface plasmon resonance. Fluorescent or magnetic labelled particles can also be used, however these require the use of an electronic reader to assess the test result.

Sandwich assays

Difference between sandwich assay and competitive assay formats of lateral flow tests

Sandwich assays are generally used for larger analytes because they tend to have multiple binding sites. As the sample migrates through the assay it first encounters a conjugate, which is an antibody specific to the target analyte labelled with a visual tag, usually colloidal gold. The antibodies bind to the target analyte within the sample and migrate together until they reach the test line. The test line also contains immobilized antibodies specific to the target analyte, which bind to the migrated analyte bound conjugate molecules. The test line then presents a visual change due to the concentrated visual tag, hence confirming the presence of the target molecules. The majority of sandwich assays also have a control line which will appear whether or not the target analyte is present to ensure proper function of the lateral flow pad.

The rapid, low-cost sandwich-based assay is commonly used for home pregnancy tests which detect human chorionic gonadotropin, hCG, in the urine of pregnant women.

Competitive assays

Competitive assays are generally used for smaller analytes since smaller analytes have fewer binding sites. The sample first encounters antibodies to the target analyte labelled with a visual tag (colored particles). The test line contains the target analyte fixed to the surface. When the target analyte is absent from the sample, unbound antibody will bind to these fixed analyte molecules, meaning that a visual marker will show. Conversely, when the target analyte is present in the sample, it binds to the antibodies to prevent them binding to the fixed analyte in the test line, and thus no visual marker shows. This differs from sandwich assays in that no band means the analyte is present.

Quantitative tests

Most LFTs are intended to operate on a purely qualitative basis. However it is possible to measure the intensity of the test line to determine the quantity of analyte in the sample. Handheld diagnostic devices known as lateral flow readers are used by several companies to provide a fully quantitative assay result. By utilizing unique wavelengths of light for illumination in conjunction with either CMOS or CCD detection technology, a signal rich image can be produced of the actual test lines. Using image processing algorithms specifically designed for a particular test type and medium, line intensities can then be correlated with analyte concentrations. One such handheld lateral flow device platform is made by Detekt Biomedical L.L.C.. Alternative non-optical techniques are also able to report quantitative assays results. One such example is a magnetic immunoassay (MIA) in the LFT form also allows for getting a quantified result. Reducing variations in the capillary pumping of the sample fluid is another approach to move from qualitative to quantitative results. Recent work has, for example, demonstrated capillary pumping with a constant flow rate independent from the liquid viscosity and surface energy.

Mobile phones have demonstrated to have a strong potential for the quantification in lateral flow assays, not only by using the camera of the device, but also the light sensor or the energy supplied by the mobile phone battery.

Control line

While not strictly necessary, most tests will incorporate a second line which contains an antibody that picks up free latex or gold in order to confirm the test has operated correctly.

Blood plasma extraction

Because the intense red color of hemoglobin interferes with the readout of colorimetric or optical detection-based diagnostic tests, blood plasma separation is a common first step to increase diagnostic test accuracy. Plasma can be extracted from whole blood via integrated filters or via agglutination.

Speed and simplicity

Time to obtain the test result is a key driver for these products. Tests can take as little as a few minutes to develop. Generally there is a trade off between time and sensitivity: more sensitive tests may take longer to develop. The other key advantage of this format of test compared to other immunoassays is the simplicity of the test, by typically requiring little or no sample or reagent preparation.

Patents

This is a highly competitive area and a number of people claim patents in the field, most notably Alere (formerly Inverness Medical Innovations, now owned by Abbott) who own patents originally filed by Unipath. A group of competitors are challenging the validity of the patents. A number of other companies also hold patents in this arena.

Applications

Lateral flow assays have a wide array of applications and can test a variety of samples like urine, blood, saliva, sweat, serum, and other fluids. They are currently used by clinical laboratories, hospitals, and physicians for quick and accurate tests for specific target molecules and gene expression. Other uses for lateral flow assays are food and environmental safety and veterinary medicine for chemicals such as diseases and toxins. LFTs are also commonly used for disease identification such as ebola, but the most common LFT is the home pregnancy test.

COVID-19 testing

Main article: COVID-19 rapid antigen test

Lateral flow assays have played a critical role in COVID-19 testing as they have the benefit of delivering a result in 15–30 minutes. The systematic evaluation of lateral flow assays during the COVID-19 pandemic was initiated at Oxford University as part of a UK collaboration with Public Health England. A study which started in June 2020 in the United Kingdom, FALCON-C19, confirmed the sensitivity of some lateral flow devices (LFDs) in this setting. Four out of 64 LFDs tested had desirable performance characteristics; the Innova SARS-CoV-2 Antigen Rapid Qualitative Test, in particular, underwent extended clinical assessment in field studies and was found to have good viral antigen detection/sensitivity with excellent specificity, although kit failure rates and the impact of training were potential issues. Following evaluation, the UK government decided in January 2021 to open secondary schools in England, with pupils and teachers taking daily LFTs, part of what was termed "Operation Moonshot". However, on 19 January 2021 the MHRA did not authorise daily rapid-turnaround tests as an alternative to self-isolation.

LFTs have been used for mass testing for COVID-19 globally and complement other public health measures for COVID-19.

Some scientists outside government have expressed serious misgivings about the use of Innova LFDs for screening for Covid. According to Jon Deeks, a professor of biostatistics at the University of Birmingham, England, the Innova test is "entirely unsuitable" for community testing: "as the test may miss up to half of cases, a negative test result indicates a reduced risk of Covid, but does not exclude Covid". Following criticism by experts and lack of authorisation by the regulator, the UK government "paused" the daily LFTs in English schools in mid-January 2021.




[[File:Lab on a Chip (7788250170).jpg|thumb|Lab-on-a-chip device]]

Et lab-on-a-chip (LOC) er en enhed, der integrerer en eller flere laboratoriefunktioner på et enkelt integreret kredsløb (almindeligvis kaldet en "chip") på kun millimeter til et par kvadratcentimeter for at opnå automatisering og screening med høj kapacitet. LOC'er kan håndtere ekstremt små væskemængder ned til mindre end picoliter. Lab-on-a-chip-enheder er en delmængde af MEMS-enheder (mikroelektromekaniske systemer) og kaldes undertiden "mikroanalysesystemer" (µTAS). LOC'er kan anvende mikrofluidik, dvs. fysik, manipulation og undersøgelse af meget små væskemængder. Strengt betragtet er "lab-on-a-chip" dog generelt en betegnelse for skalering af enkelte eller flere laboratorieprocesser ned til chip-format, mens "µTAS" er dedikeret til integration af den samlede sekvens af laboratorieprocesser til kemisk analyse. Udtrykket "lab-on-a-chip" blev indført, da det viste sig, at µTAS-teknologier kunne anvendes til mere end blot analyseformål.

==Historie==
Efter opfindelsen af mikroteknologien (~1954) til fremstilling af integrerede halvlederstrukturer til mikroelektroniske chips blev disse litografibaserede teknologier snart også anvendt til fremstilling af tryksensorer (1966). På grund af videreudviklingen af disse normalt CMOS-kompatible processer blev der også en værktøjskasse til rådighed til at skabe mekaniske strukturer i mikrometer- eller submikrometerstørrelse i siliciumskiver: æraen for mikroelektromekaniske systemer (MEMS) var begyndt.

Ved siden af tryksensorer, airbag-sensorer og andre mekanisk bevægelige strukturer blev der udviklet væskehåndteringsanordninger. Som eksempler kan nævnes: kanaler (kapillærforbindelser), blandere, ventiler, pumper og doseringsanordninger. Det første LOC-analysesystem var en gaskromatograf, der blev udviklet i 1979 af S.C. Terry på Stanford University. Det var imidlertid først i slutningen af 1980'erne og begyndelsen af 1990'erne, at LOC-forskningen for alvor begyndte at vokse, da nogle få forskningsgrupper i Europa udviklede mikropumper, flowsensorer og koncepter for integreret væskebehandling til analysesystemer. Disse µTAS-koncepter viste, at integration af forbehandlingstrin, som normalt udføres i laboratorieskala, kunne udvide den simple sensorfunktionalitet til en komplet laboratorieanalyse, herunder yderligere rensnings- og separationstrin.

Et stort løft i forskning og kommerciel interesse kom i midten af 1990'erne, da µTAS-teknologier viste sig at give interessante værktøjer til genomforskningsapplikationer som f.eks. kapillarelektroforese og DNA-mikroarrays. Et stort løft i forskningsstøtten kom også fra militæret, især fra DARPA (Defense Advanced Research Projects Agency), som var interesseret i bærbare systemer til detektion af bio/kemiske krigsstoffer. Merværdien var ikke kun begrænset til integration af laboratorieprocesser til analyse, men også til de enkelte komponenters karakteristiske muligheder og anvendelsen på andre laboratorieprocesser, der ikke vedrører analyse. Derfor blev begrebet "lab-on-a-chip" indført.

Selv om anvendelsen af LOC'er stadig er ny og beskeden, kan der konstateres en stigende interesse fra virksomheder og anvendte forskningsgrupper inden for forskellige områder som f.eks. analyse (f.eks. kemisk analyse, miljøovervågning, medicinsk diagnostik og cellomik), men også inden for syntetisk kemi (f.eks. hurtig screening og mikroreaktorer til farmaceutisk brug). Ud over yderligere udvikling af anvendelsesmuligheder forventes forskningen i LOC-systemer også at blive udvidet til at omfatte nedskalering af væskehåndteringsstrukturer ved hjælp af nanoteknologi. Kanaler i submikrometer- og nanostørrelse, DNA-labyrinter, enkeltcelledetektion og -analyse samt nanosensorer kan blive mulige og give mulighed for nye måder at interagere med biologiske arter og store molekyler på. Der er skrevet mange bøger om forskellige aspekter af disse anordninger, herunder væsketransport, systemegenskaber, sensorteknikker og bioanalytiske anvendelser.

==Chipmaterialer og fremstillingsteknologier==
Grundlaget for de fleste LOC-fabrikationsprocesser er fotolitografi. Oprindeligt var de fleste processer i silicium, da disse veludviklede teknologier var direkte afledt af halvlederfremstilling. På grund af krav om f.eks. specifikke optiske egenskaber, bio- eller kemisk kompatibilitet, lavere produktionsomkostninger og hurtigere prototypefremstilling er der blevet udviklet nye processer såsom ætsning, udfældning og binding af glas, keramik og metal, polydimethylsiloxan (PDMS)-behandling (f.eks. blød litografi), behandling af off-stoiometriske thiol-en-polymerer (OSTEmer), tykfilm- og stereolitografibaseret 3D-printning samt hurtige replikationsmetoder via galvanisering, sprøjtestøbning og prægning. Efterspørgslen efter billige og nemme LOC-prototyper resulterede i en enkel metode til fremstilling af PDMS-mikrofluidiske anordninger: ESCARGOT (Embedded SCAffold RemovinG Open Technology). Denne teknik gør det muligt at skabe mikrofluidiske kanaler i en enkelt blok af PDMS via en opløseligt stillads (fremstillet ved f.eks. 3D-printning). Desuden overskrider LOC-området mere og mere grænserne mellem litografibaseret mikrosystemteknologi, nanoteknologi og finmekanik.

==Fordele==
LOC'er kan give fordele, som er specifikke for deres anvendelse. Typiske fordele er:

* lavt forbrug af væskemængder (mindre spild, lavere omkostninger til reagenser og færre nødvendige prøvevolumener til diagnostik)
* hurtigere analyse- og svartider på grund af korte diffusionsafstande, hurtig opvarmning, højt overflade/volumen-forhold og lille varmekapacitet.
* bedre processtyring på grund af systemets hurtigere respons (f.eks. termisk styring af eksoterme kemiske reaktioner)
* kompakte systemer på grund af integration af mange funktioner og små volumener
* massiv parallelisering på grund af kompakthed, hvilket muliggør analyser med højt gennemløb
* lavere fremstillingsomkostninger, hvilket giver mulighed for omkostningseffektive engangschips, der kan fremstilles i masseproduktion
* delkvaliteten kan kontrolleres automatisk
* sikrere platform til kemiske, radioaktive eller biologiske undersøgelser på grund af integration af funktionalitet, mindre væskevolumener og lagret energi

==Ulemper==

De mest fremtrædende ulemper ved labs-on-chip er følgende:

* Den mikroproduktionsproces, der er nødvendig for at fremstille dem, er kompleks og arbejdskrævende og kræver både dyrt udstyr og specialiseret personale. Det kan overvindes ved hjælp af de seneste teknologiske fremskridt inden for billig 3D-printning og lasergravering.
* Det komplekse væskeaktiveringsnetværk kræver flere pumper og stik, hvor det er vanskeligt at foretage finkontrol. Dette kan overvindes ved omhyggelig simulering, en indbygget pumpe, f.eks. en chip med en luftpose, eller ved at bruge en centrifugalkraft til at erstatte pumpningen, dvs. en centrifugalmikrofluidisk biochip.
* De fleste LOC'er er nye konceptprøvninger, som endnu ikke er fuldt udviklet til udbredt brug. Der er behov for flere valideringer, før de kan anvendes i praksis.
I den mikroliterskala, som LOC'er beskæftiger sig med, er overfladeafhængige virkninger som f.eks. kapillærkræfter, overfladeruhed eller kemiske interaktioner mere dominerende. Dette kan undertiden gøre det ret udfordrende og mere komplekst at efterligne laboratorieprocesser i LOC'er end i konventionelt laboratorieudstyr.
* Detektionsprincipper kan ikke altid nedskaleres på en positiv måde, hvilket fører til et lavt signal/støj-forhold.

==Global sundhed==
Lab-on-a-chip-teknologi kan snart blive en vigtig del af bestræbelserne på at forbedre den globale sundhed, især gennem udvikling af udstyr til point-of-care-testning. I lande med få sundhedsressourcer er smitsomme sygdomme, som ville kunne behandles i et udviklet land, ofte dødelige. I nogle tilfælde har fattige sundhedsklinikker lægemidler til behandling af en bestemt sygdom, men mangler diagnostiske redskaber til at identificere de patienter, der bør modtage lægemidlerne. Mange forskere mener, at LOC-teknologi kan være nøglen til nye effektive diagnostiske instrumenter. Disse forskeres mål er at skabe mikrofluidiske chips, som vil gøre det muligt for sundhedspersoner på dårligt udstyrede klinikker at udføre diagnostiske test såsom mikrobiologiske kulturanalyser, immunoassays og nukleinsyreanalyser uden laboratoriehjælp.

=== Globale udfordringer ==

For at chipsene kan anvendes i områder med begrænsede ressourcer, skal der overvindes mange udfordringer. I de udviklede lande er de mest værdsatte egenskaber ved diagnostiske værktøjer hastighed, følsomhed og specificitet; men i lande, hvor sundhedsinfrastrukturen er mindre veludviklet, skal egenskaber som brugervenlighed og holdbarhed også tages i betragtning. De reagenser, der følger med chippen, skal f.eks. være udformet således, at de forbliver effektive i månedsvis, selv om chippen ikke opbevares i et klimakontrolleret miljø. Chipdesignere skal også have omkostningerne, skalerbarhed og genanvendelighed i tankerne, når de vælger, hvilke materialer og fremstillingsteknikker der skal anvendes.

=== Eksempler på global LOC-anvendelse ==
Et af de mest fremtrædende og velkendte LOC-enheder, der er kommet på markedet, er graviditetstestsættet til hjemmebrug, en enhed, der anvender papirbaseret mikrofluidikteknologi. Et andet aktivt område inden for LOC-forskning vedrører metoder til diagnosticering og håndtering af almindelige infektionssygdomme forårsaget af bakterier, f.eks. bakteriuri, eller virus, f.eks. influenza. En guldstandard til diagnosticering af bakteriuri (urinvejsinfektioner) er mikrobiologisk dyrkning. En nyere undersøgelse baseret på laboratorie-på-en-chip-teknologi, Digital Dipstick, har miniaturiseret mikrobiologisk dyrkning til et pindformat og gjort det muligt at anvende den på stedet. Når det gælder virusinfektioner, er HIV-infektioner et godt eksempel. Omkring 36,9 millioner mennesker er smittet med hiv i verden i dag, og 59 % af disse mennesker modtager antiretroviral behandling. Kun 75 % af de mennesker, der lever med hiv, kendte deres hiv-status. Måling af antallet af CD4+ T-lymfocytter i en persons blod er en præcis måde at fastslå, om en person har hiv, og at følge forløbet af en hiv-infektion på. I øjeblikket er flowcytometri den gyldne standard til at bestemme CD4-tallet, men flowcytometri er en kompliceret teknik, som ikke er tilgængelig i de fleste udviklingsområder, fordi den kræver uddannede teknikere og dyrt udstyr. For nylig blev der udviklet et sådant cytometer til kun 5 dollars. Et andet aktivt område inden for LOC-forskning er kontrolleret separation og blanding. Med sådanne apparater er det muligt hurtigt at diagnosticere og potentielt behandle sygdomme. Som nævnt ovenfor er en stor motivation for udvikling af disse apparater, at de potentielt kan fremstilles til meget lave omkostninger. Endnu et forskningsområde, der undersøges i forbindelse med LOC, er sikkerhed i hjemmet. Automatiseret overvågning af flygtige organiske forbindelser (VOC) er en ønsket funktion for LOC. Hvis denne anvendelse bliver pålidelig, kan disse mikroenheder installeres på globalt plan og underrette boligejerne om potentielt farlige forbindelser.

== Plantevidenskab ==
Lab-on-a-chip-enheder kunne bruges til at karakterisere pollenrørets føring i Arabidopsis thaliana. Plant on a chip er en miniatureanordning, hvori pollenvæv og ægceller kan inkuberes med henblik på plantevidenskabelige undersøgelser.

== Bibliografi ==
* Geschke, Klank & Telleman, eds.: Microsystem Engineering of Lab-on-a-chip Devices, 1st ed, John Wiley & Sons. {{ISBN|3-527-30733-8}}.
* {{cite book |editor= Herold, KE |editor2= Rasooly, A| year= 2009|title=Lab-on-a-Chip Technology: Fabrication and Microfluidics | publisher=Caister Academic Press | isbn= 978-1-904455-46-2}}
* {{cite book |editor= Herold, KE |editor2= Rasooly, A| year= 2009|title=Lab-on-a-Chip Technology: Biomolecular Separation and Analysis | publisher=Caister Academic Press | isbn= 978-1-904455-47-9}}
* {{cite book |author1=Yehya H. Ghallab |author2=Wael Badawy | year= 2010|title=Lab-on-a-chip: Techniques, Circuits, and Biomedical Applications | publisher=Artech House | isbn= 978-1-59693-418-4| pages=220}}
* (2012) Gareth Jenkins & Colin D Mansfield (eds): [https://www.springer.com/chemistry/biotechnology/book/978-1-62703-133-2 Methods in Molecular Biology – Microfluidic Diagnostics], Humana Press, {{ISBN|978-1-62703-133-2}}

== Eksterne henvisninger ==
{{Commonskat|Lab-on-a-chip devices}}
{{Autoritetsdata}}

[[Kategori:Nanoteknologi]]


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Revisão das 05h46min de 22 de maio de 2021