High-throughput screening ( HTS ) is a method for scientific discovery especially used in drug discovery and relevant to the fields of biology , materials science and chemistry . Using robotics , data processing/control software, liquid handling devices, and sensitive detectors, high-throughput screening allows a researcher to quickly conduct millions of chemical, genetic, or pharmacological tests. Through this process one can quickly recognize active compounds, antibodies, or genes that modulate a particular biomolecular pathway. The results of these experiments provide starting points for drug design and for understanding the noninteraction or role of a particular location.
90-610: The abbreviation MSSR can refer to various concepts: The Molecular Screening Shared Resource (2004-Present), a facility at the University of California, Los Angeles, Dedicated to High-throughput_screening . The Moldavian Soviet Socialist Republic (1940-1991), a constituent republic of the Soviet Union . A Monopulse Secondary Surveillance Radar , an advanced secondary surveillance radar . The Marine Scout Sniper Rifle ,
180-481: A lawyer , doctor , engineer , journalist are at risk of automation. Prospects are particularly bleak for occupations that do not presently require a university degree, such as truck driving. Even in high-tech corridors like Silicon Valley , concern is spreading about a future in which a sizable percentage of adults have little chance of sustaining gainful employment. "In The Second Machine Age, Erik Brynjolfsson and Andrew McAfee argue that "...there's never been
270-415: A ResonantAcoustic mixer, Merck reported reduced processing time to less than 2 hours on only 1-2 mg of drug compound per well. Merck also indicated the acoustic milling approach allows for the preparation of high dose nanosuspension formulations that could not be obtained using conventional milling equipment. Whereby traditional HTS drug discovery uses purified proteins or intact cells, recent development of
360-420: A better time to be a worker with special skills or the right education, because these people can use technology to create and capture value. However, there's never been a worse time to be a worker with only 'ordinary' skills and abilities to offer, because computers, robots, and other digital technologies are acquiring these skills and abilities at an extraordinary rate." As the example of Sweden suggests, however,
450-442: A consequence, robust methods such as the z*-score method, SSMD*, B-score method, and quantile-based method have been proposed and adopted for hit selection. In a screen with replicates, we can directly estimate variability for each compound; as a consequence, we should use SSMD or t-statistic that does not rely on the strong assumption that the z-score and z*-score rely on. One issue with the use of t-statistic and associated p-values
540-584: A desired size of effects in an HTS is called a hit. The process of selecting hits is called hit selection. The analytic methods for hit selection in screens without replicates (usually in primary screens) differ from those with replicates (usually in confirmatory screens). For example, the z-score method is suitable for screens without replicates whereas the t-statistic is suitable for screens with replicates. The calculation of SSMD for screens without replicates also differs from that for screens with replicates . For hit selection in primary screens without replicates,
630-679: A gatekeeper for excellent quality assays. In a typical HTS experiment, a clear distinction between a positive control and a negative reference such as a negative control is an index for good quality. Many quality-assessment measures have been proposed to measure the degree of differentiation between a positive control and a negative reference. Signal-to-background ratio, signal-to-noise ratio, signal window, assay variability ratio, and Z-factor have been adopted to evaluate data quality. Strictly standardized mean difference ( SSMD ) has recently been proposed for assessing data quality in HTS assays. A compound with
720-446: A good thing, due to the country's still-powerful unions and a more robust national safety net . In the U.S., 47% of all current jobs have the potential to be fully automated by 2033, according to the research of experts Carl Benedikt Frey and Michael Osborne. Furthermore, wages and educational attainment appear to be strongly negatively correlated with an occupation's risk of being automated. Even highly skilled professional jobs like
810-454: A home in the banking industry. It can range from simple on-off control to multi-variable high-level algorithms in terms of control complexity. In the simplest type of an automatic control loop , a controller compares a measured value of a process with a desired set value and processes the resulting error signal to change some input to the process, in such a way that the process stays at its set point despite disturbances. This closed-loop control
900-440: A large amount of electricity. Call volume eventually grew so fast that it was feared the telephone system would consume all electricity production, prompting Bell Labs to begin research on the transistor . The logic performed by telephone switching relays was the inspiration for the digital computer. The first commercially successful glass bottle-blowing machine was an automatic model introduced in 1905. The machine, operated by
990-418: A library of stock plates , whose contents are carefully catalogued, and each of which may have been created by the lab or obtained from a commercial source. These stock plates themselves are not directly used in experiments; instead, separate assay plates are created as needed. An assay plate is simply a copy of a stock plate, created by pipetting a small amount of liquid (often measured in nanoliters ) from
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#17327837609551080-667: A library of over 380,000 compounds. Northwestern University's High Throughput Analysis Laboratory supports target identification, validation, assay development, and compound screening. The non-profit Sanford Burnham Prebys Medical Discovery Institute also has a long-standing HTS facility in the Conrad Prebys Center for Chemical Genomics which was part of the MLPCN. The non-profit Scripps Research Molecular Screening Center (SRMSC) continues to serve academia across institutes post-MLPCN era. The SRMSC uHTS facility maintains one of
1170-401: A machine where a precise differential must be maintained between the sections. In steel rolling, the metal elongates as it passes through pairs of rollers, which must run at successively faster speeds. In paper making paper, the sheet shrinks as it passes around steam-heated drying arranged in groups, which must run at successively slower speeds. The first application of a sectional electric drive
1260-423: A more physiologically relevant format. HTS is a relatively recent innovation, made feasible largely through modern advances in robotics and high-speed computer technology. It still takes a highly specialized and expensive screening lab to run an HTS operation, so in many cases a small- to moderate-size research institution will use the services of an existing HTS facility rather than set up one for itself. There
1350-455: A negative impact on employment and wages when robots are introduced to an industry. When one robot is added per one thousand workers, the employment to population ratio decreases between 0.18 and 0.34 percentages and wages are reduced by 0.25–0.5 percentage points. During the time period studied, the US did not have many robots in the economy which restricts the impact of automation. However, automation
1440-493: A number of experiments on the wells (such as shining polarized light on them and measuring reflectivity, which can be an indication of protein binding). In this case, the machine outputs the result of each experiment as a grid of numeric values, with each number mapping to the value obtained from a single well. A high-capacity analysis machine can measure dozens of plates in the space of a few minutes like this, generating thousands of experimental datapoints very quickly. Depending on
1530-437: A punch-card system to program looms. In 1771 Richard Arkwright invented the first fully automated spinning mill driven by water power, known at the time as the water frame . An automatic flour mill was developed by Oliver Evans in 1785, making it the first completely automated industrial process. A centrifugal governor was used by Mr. Bunce of England in 1784 as part of a model steam crane . The centrifugal governor
1620-463: A scientist does not understand some statistics or rudimentary data-handling technologies, he or she may not be considered to be a true molecular biologist and, thus, will simply become "a dinosaur." High-quality HTS assays are critical in HTS experiments. The development of high-quality HTS assays requires the integration of both experimental and computational approaches for quality control (QC). Three important means of QC are (i) good plate design, (ii)
1710-431: A short-term solution as it doesn't fully address the issue of income inequality which will be exacerbated by job displacement. Lights-out manufacturing is a production system with no human workers, to eliminate labor costs. Lights out manufacturing grew in popularity in the U.S. when General Motors in 1982 implemented humans "hands-off" manufacturing to "replace risk-averse bureaucracy with automation and robots". However,
1800-403: A silicon sheet of lenses that can be placed over microfluidic arrays to allow the fluorescence measurement of 64 different output channels simultaneously with a single camera. This process can analyze 200,000 drops per second. In 2013, researchers have disclosed an approach with small molecules from plants. In general, it is essential to provide high-quality proof-of-concept validations early in
1890-777: A single construct such as a single siRNA or cDNA. Functional genomics is typically paired with high content screening using e.g. epifluorescent microscopy or laser scanning cytometry. The University of Illinois also has a facility for HTS, as does the University of Minnesota. The Life Sciences Institute at the University of Michigan houses the HTS facility in the Center for Chemical Genomics. Columbia University has an HTS shared resource facility with ~300,000 diverse small molecules and ~10,000 known bioactive compounds available for biochemical, cell-based and NGS-based screening. The Rockefeller University has an open-access HTS Resource Center HTSRC (The Rockefeller University, HTSRC ), which offers
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#17327837609551980-563: A sniper rifle developed by the Philippine Marine Corps . Topics referred to by the same term [REDACTED] This disambiguation page lists articles associated with the title MSSR . If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=MSSR&oldid=1068494908 " Category : Disambiguation pages Hidden categories: Short description
2070-599: A study published in McKinsey Quarterly in 2015 the impact of computerization in most cases is not the replacement of employees but the automation of portions of the tasks they perform. The methodology of the McKinsey study has been heavily criticized for being intransparent and relying on subjective assessments. The methodology of Frey and Osborne has been subjected to criticism, as lacking evidence, historical awareness, or credible methodology. Additionally,
2160-430: A two-man crew working 12-hour shifts, could produce 17,280 bottles in 24 hours, compared to 2,880 bottles made by a crew of six men and boys working in a shop for a day. The cost of making bottles by machine was 10 to 12 cents per gross compared to $ 1.80 per gross by the manual glassblowers and helpers. Sectional electric drives were developed using control theory. Sectional electric drives are used on different sections of
2250-472: A very challenging drug target. Hits are confirmed at the screening step due to the bell-shaped curve. This method is very similar to the quantitative HTS method (screening and hit confirmation at the same time), except that using this approach greatly decreases the data point number and can screen easily more than 100.000 biological relevant compounds. Switching from an orbital shaker, which required milling times of 24 hours and at least 10 mg of drug compound to
2340-440: Is a trend in academia for universities to be their own drug discovery enterprise. These facilities, which normally are found only in industry, are now increasingly found at universities as well. UCLA , for example, features an open access HTS laboratory Molecular Screening Shared Resources (MSSR, UCLA), which can screen more than 100,000 compounds a day on a routine basis. The open access policy ensures that researchers from all over
2430-416: Is also loosely associated with mechanization, machines replacing human labor. Coupled with mechanization, extending human capabilities in terms of size, strength, speed, endurance, visual range & acuity, hearing frequency & precision, electromagnetic sensing & effecting, etc., advantages include: The main disadvantages of automation are: The paradox of automation says that the more efficient
2520-462: Is also thought to impact the environment. A study of energy consumption of automated homes in Finland showed that smart homes could reduce energy consumption by monitoring levels of consumption in different areas of the home and adjusting consumption to reduce energy leaks (e.g. automatically reducing consumption during the nighttime when activity is low). This study, along with others, indicated that
2610-449: Is an application of negative feedback to a system. The mathematical basis of control theory was begun in the 18th century and advanced rapidly in the 20th. The term automation , inspired by the earlier word automatic (coming from automaton ), was not widely used before 1947, when Ford established an automation department. It was during this time that the industry was rapidly adopting feedback controllers , which were introduced in
2700-403: Is comparable across experiments and, thus, we can use the same cutoff for the population value of SSMD to measure the size of compound effects . Unique distributions of compounds across one or many plates can be employed either to increase the number of assays per plate or to reduce the variance of assay results, or both. The simplifying assumption made in this approach is that any N compounds in
2790-458: Is different from Wikidata All article disambiguation pages All disambiguation pages High-throughput screening The key labware or testing vessel of HTS is the microtiter plate , which is a small container, usually disposable and made of plastic, that features a grid of small, open divots called wells . In general, microplates for HTS have either 96, 192, 384, 1536, 3456 or 6144 wells. These are all multiples of 96, reflecting
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2880-517: Is done with robots and automatic welders are used in applications like pipelines. With the advent of the space age in 1957, controls design, particularly in the United States, turned away from the frequency-domain techniques of classical control theory and backed into the differential equation techniques of the late 19th century, which were couched in the time domain. During the 1940s and 1950s, German mathematician Irmgard Flugge-Lotz developed
2970-605: Is expected to triple (conservative estimate) or quadruple (a generous estimate) leading these numbers to become substantially higher. Based on a formula by Gilles Saint-Paul , an economist at Toulouse 1 University , the demand for unskilled human capital declines at a slower rate than the demand for skilled human capital increases. In the long run and for society as a whole it has led to cheaper products, lower average work hours , and new industries forming (i.e., robotics industries, computer industries, design industries). These new industries provide many high salary skill-based jobs to
3060-844: Is tested across four- to five-orders of magnitude of concentrations. Automation 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 machines. Automation has been achieved by various means including mechanical , hydraulic , pneumatic , electrical , electronic devices , and computers , usually in combination. Complicated systems, such as modern factories , airplanes , and ships typically use combinations of all of these techniques. The benefit of automation includes labor savings, reducing waste, savings in electricity costs, savings in material costs, and improvements to quality, accuracy, and precision. Automation includes
3150-411: Is that they are affected by both sample size and effect size. They come from testing for no mean difference, and thus are not designed to measure the size of compound effects. For hit selection, the major interest is the size of effect in a tested compound. SSMD directly assesses the size of effects. SSMD has also been shown to be better than other commonly used effect sizes. The population value of SSMD
3240-480: Is the increased demand for flexibility and convertibility in manufacturing processes . Manufacturers are increasingly demanding the ability to easily switch from manufacturing Product A to manufacturing Product B without having to completely rebuild the production lines . Flexibility and distributed processes have led to the introduction of Automated Guided Vehicles with Natural Features Navigation. Digital electronics helped too. Former analog-based instrumentation
3330-413: Is the most likely agent, while also providing three measurements of compound B's efficacy against the specified target. Commercial applications of this approach involve combinations in which no two compounds ever share more than one well, to reduce the (second-order) possibility of interference between pairs of compounds being screened. Automation and low volume assay formats were leveraged by scientists at
3420-487: The Industrial Revolution , when inventions like the steam engine were making some job categories expendable, workers forcefully resisted these changes. Luddites , for instance, were English textile workers who protested the introduction of weaving machines by destroying them. More recently, some residents of Chandler, Arizona , have slashed tires and pelted rocks at self-driving car , in protest over
3510-527: The Oxford Martin School argued that employees engaged in "tasks following well-defined procedures that can easily be performed by sophisticated algorithms" are at risk of displacement, and 47% of jobs in the US were at risk. The study, released as a working paper in 2013 and published in 2017, predicted that automation would put low-paid physical occupations most at risk, by surveying a group of colleagues on their opinions. However, according to
3600-554: The personal computer (1983). Perhaps the most cited advantage of automation in industry is that it is associated with faster production and cheaper labor costs. Another benefit could be that it replaces hard, physical, or monotonous work. Additionally, tasks that take place in hazardous environments or that are otherwise beyond human capabilities can be done by machines, as machines can operate even under extreme temperatures or in atmospheres that are radioactive or toxic. They can also be maintained with simple quality checks. However, at
3690-463: The steam engine created a new requirement for automatic control systems including temperature regulators (invented in 1624; see Cornelius Drebbel ), pressure regulators (1681), float regulators (1700) and speed control devices. Another control mechanism was used to tent the sails of windmills. It was patented by Edmund Lee in 1745. Also in 1745, Jacques de Vaucanson invented the first automated loom. Around 1800, Joseph Marie Jacquard created
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3780-813: The 1840s. Machine tools were automated with Numerical control (NC) using punched paper tape in the 1950s. This soon evolved into computerized numerical control (CNC). Today extensive automation is practiced in practically every type of manufacturing and assembly process. Some of the larger processes include electrical power generation, oil refining, chemicals, steel mills, plastics, cement plants, fertilizer plants, pulp and paper mills, automobile and truck assembly, aircraft production, glass manufacturing, natural gas separation plants, food and beverage processing, canning and bottling and manufacture of various kinds of parts. Robots are especially useful in hazardous applications like automobile spray painting. Robots are also used to assemble electronic circuit boards. Automotive welding
3870-440: The 1930s. The World Bank 's World Development Report of 2019 shows evidence that the new industries and jobs in the technology sector outweigh the economic effects of workers being displaced by automation. Job losses and downward mobility blamed on automation have been cited as one of many factors in the resurgence of nationalist , protectionist and populist politics in the US, UK and France, among other countries since
3960-452: The 2010s. It was a preoccupation of the Greeks and Arabs (in the period between about 300 BC and about 1200 AD) to keep accurate track of time. In Ptolemaic Egypt , about 270 BC, Ctesibius described a float regulator for a water clock , a device not unlike the ball and cock in a modern flush toilet. This was the earliest feedback-controlled mechanism. The appearance of
4050-595: The Industrial Revolution was by trial-and-error, together with a great deal of engineering intuition. It was not until the mid-19th century that the stability of feedback control systems was analyzed using mathematics, the formal language of automatic control theory. The centrifugal governor was invented by Christiaan Huygens in the seventeenth century, and used to adjust the gap between millstones . The introduction of prime movers , or self-driven machines advanced grain mills, furnaces, boilers, and
4140-508: The NIH Chemical Genomics Center (NCGC) to develop quantitative HTS (qHTS), a paradigm to pharmacologically profile large chemical libraries through the generation of full concentration-response relationships for each compound. With accompanying curve fitting and cheminformatics software qHTS data yields half maximal effective concentration (EC50), maximal response, Hill coefficient (nH) for the entire library enabling
4230-504: The Organisation for Economic Co-operation and Development ( OECD ) found that across the 21 OECD countries, 9% of jobs are automatable. The Obama administration pointed out that every 3 months "about 6 percent of jobs in the economy are destroyed by shrinking or closing businesses, while a slightly larger percentage of jobs are added." A recent MIT economics study of automation in the U.S. from 1990 to 2007 found that there may be
4320-401: The US and developed countries where technological advances contribute to higher demand for highly skilled labor but demand for middle-wage labor continues to fall. Economists call this trend "income polarization" where unskilled labor wages are driven down and skilled labor is driven up and it is predicted to continue in developed economies. Unemployment is becoming a problem in the U.S. due to
4410-502: The assessment of nascent structure activity relationships (SAR). In March 2010, research was published demonstrating an HTS process allowing 1,000 times faster screening (100 million reactions in 10 hours) at 1-millionth the cost (using 10 times the reagent volume) than conventional techniques using drop-based microfluidics. Drops of fluid separated by oil replace microplate wells and allow analysis and hit sorting while reagents are flowing through channels. In 2010, researchers developed
4500-443: The automated system, the more crucial the human contribution of the operators. Humans are less involved, but their involvement becomes more critical. Lisanne Bainbridge , a cognitive psychologist, identified these issues notably in her widely cited paper "Ironies of Automation." If an automated system has an error, it will multiply that error until it is fixed or shut down. This is where human operators come in. A fatal example of this
4590-504: The cars' perceived threat to human safety and job prospects. The relative anxiety about automation reflected in opinion polls seems to correlate closely with the strength of organized labor in that region or nation. For example, while a study by the Pew Research Center indicated that 72% of Americans are worried about increasing automation in the workplace, 80% of Swedes see automation and artificial intelligence (AI) as
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#17327837609554680-427: The compounds in the wells, measurements are taken across all the plate's wells, either manually or by a machine. Manual measurements are often necessary when the researcher is using microscopy to (for example) seek changes or defects in embryonic development caused by the wells' compounds, looking for effects that a computer could not easily determine by itself. Otherwise, a specialized automated analysis machine can run
4770-493: The data-collection process. HTS robots that can test up to 100,000 compounds per day currently exist. Automatic colony pickers pick thousands of microbial colonies for high throughput genetic screening. The term uHTS or ultra-high-throughput screening refers (circa 2008) to screening in excess of 100,000 compounds per day. With the ability of rapid screening of diverse compounds (such as small molecules or siRNAs ) to identify active compounds, HTS has led to an explosion in
4860-414: The declining influence of factory electrification. Factory productivity was greatly increased by electrification in the 1920s. U.S. manufacturing productivity growth fell from 5.2%/yr 1919–29 to 2.76%/yr 1929–41. Alexander Field notes that spending on non-medical instruments increased significantly from 1929 to 1933 and remained strong thereafter. The First and Second World Wars saw major advancements in
4950-415: The drug discovery process. Here technologies that enable the identification of potent, selective, and bioavailable chemical probes are of crucial interest, even if the resulting compounds require further optimization for development into a pharmaceutical product. Nuclear receptor RORα, a protein that has been targeted for more than a decade to identify potent and bioavailable agonists, was used as an example of
5040-473: The easily interpretable ones are average fold change, mean difference, percent inhibition, and percent activity. However, they do not capture data variability effectively. The z-score method or SSMD, which can capture data variability based on an assumption that every compound has the same variability as a negative reference in the screens. However, outliers are common in HTS experiments, and methods such as z-score are sensitive to outliers and can be problematic. As
5130-419: The economy. By 2030, between 3 and 14 percent of the global workforce will be forced to switch job categories due to automation eliminating jobs in an entire sector. While the number of jobs lost to automation is often offset by jobs gained from technological advances, the same type of job loss is not the same one replaced and that leading to increasing unemployment in the lower-middle class. This occurs largely in
5220-422: The exponential growth rate of automation and technology. According to Kim, Kim, and Lee (2017:1), "[a] seminal study by Frey and Osborne in 2013 predicted that 47% of the 702 examined occupations in the U.S. faced a high risk of decreased employment rate within the next 10–25 years as a result of computerization." As many jobs are becoming obsolete, which is causing job displacement, one possible solution would be for
5310-453: The factory never reached full "lights out" status. The expansion of lights out manufacturing requires: The costs of automation to the environment are different depending on the technology, product or engine automated. There are automated engines that consume more energy resources from the Earth in comparison with previous engines and vice versa. Hazardous operations, such as oil refining ,
5400-918: The field of mass communication and signal processing . Other key advances in automatic controls include differential equations , stability theory and system theory (1938), frequency domain analysis (1940), ship control (1950), and stochastic analysis (1941). Starting in 1958, various systems based on solid-state digital logic modules for hard-wired programmed logic controllers (the predecessors of programmable logic controllers [PLC]) emerged to replace electro-mechanical relay logic in industrial control systems for process control and automation, including early Telefunken / AEG Logistat , Siemens Simatic , Philips / Mullard / Valvo [ de ] Norbit , BBC Sigmatronic , ACEC Logacec , Akkord [ de ] Estacord , Krone Mibakron, Bistat, Datapac, Norlog, SSR, or Procontic systems. In 1959 Texaco 's Port Arthur Refinery became
5490-484: The first chemical plant to use digital control . Conversion of factories to digital control began to spread rapidly in the 1970s as the price of computer hardware fell. The automatic telephone switchboard was introduced in 1892 along with dial telephones. By 1929, 31.9% of the Bell system was automatic. Automatic telephone switching originally used vacuum tube amplifiers and electro-mechanical switches, which consumed
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#17327837609555580-452: The function of each gene in the context of interest by either knocking each gene out or overexpressing it. Parallel access to high-throughput small molecule screen and a genome wide screen enables researchers to perform target identification and validation for given disease or the mode of action determination on a small molecule. The most accurate results can be obtained by use of "arrayed" functional genomics libraries, i.e. each library contains
5670-523: The government to assist with a universal basic income (UBI) program. UBI would be a guaranteed, non-taxed income of around 1000 dollars per month, paid to all U.S. citizens over the age of 21. UBI would help those who are displaced take on jobs that pay less money and still afford to get by. It would also give those that are employed with jobs that are likely to be replaced by automation and technology extra money to spend on education and training on new demanding employment skills. UBI, however, should be seen as
5760-582: The largest library collections in academia, presently at well-over 665,000 small molecule entities, and routinely screens the full collection or sub-libraries in support of multi-PI grant initiatives. In the United States, the National Institutes of Health or NIH has created a nationwide consortium of small-molecule screening centers to produce innovative chemical tools for use in biological research. The Molecular Libraries Probe Production Centers Network, or MLPCN, performs HTS on assays provided by
5850-601: The manufacturing of industrial chemicals , and all forms of metal working , were always early contenders for automation. The automation of vehicles could prove to have a substantial impact on the environment, although the nature of this impact could be beneficial or harmful depending on several factors. Because automated vehicles are much less likely to get into accidents compared to human-driven vehicles, some precautions built into current models (such as anti-lock brakes or laminated glass ) would not be required for self-driving versions. Removal of these safety features reduces
5940-526: The mechanical clock in the 14th century made the water clock and its feedback control system obsolete. The Persian Banū Mūsā brothers, in their Book of Ingenious Devices (850 AD), described a number of automatic controls. Two-step level controls for fluids, a form of discontinuous variable structure controls , were developed by the Banu Musa brothers. They also described a feedback controller . The design of feedback control systems up through
6030-514: The operation of new high-pressure boilers, steam turbines and electrical substations created a large demand for instruments and controls. Central control rooms became common in the 1920s, but as late as the early 1930s, most process controls were on-off. Operators typically monitored charts drawn by recorders that plotted data from instruments. To make corrections, operators manually opened or closed valves or turned switches on or off. Control rooms also used color-coded lights to send signals to workers in
6120-503: The original 96-well microplate with spaced wells of 8 x 12 with 9 mm spacing. Most of the wells contain test items, depending on the nature of the experiment. These could be different chemical compounds dissolved e.g. in an aqueous solution of dimethyl sulfoxide (DMSO). The wells could also contain cells or enzymes of some type. (The other wells may be empty or contain pure solvent or untreated samples, intended for use as experimental controls .) A screening facility typically holds
6210-406: The plant to manually make certain changes. The development of the electronic amplifier during the 1920s, which was important for long-distance telephony, required a higher signal-to-noise ratio, which was solved by negative feedback noise cancellation. This and other telephony applications contributed to the control theory. In the 1940s and 1950s, German mathematician Irmgard Flügge-Lotz developed
6300-475: The rate of data generated in recent years . Consequently, one of the most fundamental challenges in HTS experiments is to glean biochemical significance from mounds of data, which relies on the development and adoption of appropriate experimental designs and analytic methods for both quality control and hit selection . HTS research is one of the fields that have a feature described by John Blume, Chief Science Officer for Applied Proteomics, Inc., as follows: Soon, if
6390-712: The research community, against a large library of small molecules maintained in a central molecule repository. In addition, the NIH created the National Center for Advancing Translational Sciences or NCATS, housed in Shady Grove Maryland, that carries out small molecule and RNAi screens in collaboration with academic laboratories. Of note, the small molecule screening uses 1536 well plates, a capability rarely seen in academic screening laboratories that allows one to carry out quantitative HTS in which each compound
6480-712: The results of this first assay, the researcher can perform follow up assays within the same screen by "cherrypicking" liquid from the source wells that gave interesting results (known as "hits") into new assay plates, and then re-running the experiment to collect further data on this narrowed set, confirming and refining observations. Automation is an essential element in HTS's usefulness. Typically, an integrated robot system consisting of one or more robots transports assay-microplates from station to station for sample and reagent addition, mixing, incubation, and finally readout or detection. An HTS system can usually prepare, incubate, and analyze many plates simultaneously, further speeding
6570-405: The same well will not typically interact with each other, or the assay target, in a manner that fundamentally changes the ability of the assay to detect true hits. For example, imagine a plate wherein compound A is in wells 1–2–3, compound B is in wells 2–3–4, and compound C is in wells 3–4–5. In an assay of this plate against a given target, a hit in wells 2, 3, and 4 would indicate that compound B
6660-500: The selection of effective positive and negative chemical/biological controls, and (iii) the development of effective QC metrics to measure the degree of differentiation so that assays with inferior data quality can be identified. A good plate design helps to identify systematic errors (especially those linked with well position) and determine what normalization should be used to remove/reduce the impact of systematic errors on both QC and hit selection. Effective analytic QC methods serve as
6750-567: The smart home's ability to monitor and adjust consumption levels would reduce unnecessary energy usage. However, some research suggests that smart homes might not be as efficient as non-automated homes. A more recent study has indicated that, while monitoring and adjusting consumption levels do decrease unnecessary energy use, this process requires monitoring systems that also consume an amount of energy. The energy required to run these systems sometimes negates their benefits, resulting in little to no ecological benefit. Another major shift in automation
6840-473: The steam engine stayed well ahead of science, both thermodynamics and control theory. The governor received relatively little scientific attention until James Clerk Maxwell published a paper that established the beginning of a theoretical basis for understanding control theory. Relay logic was introduced with factory electrification , which underwent rapid adaption from 1900 through the 1920s. Central electric power stations were also undergoing rapid growth and
6930-439: The technology is associated with the use of intact living organisms, like the nematode Caenorhabditis elegans and zebrafish ( Danio rerio ). In 2016-2018 plate manufacturers began producing specialized chemistry to allow for mass production of ultra-low adherent cell repellent surfaces which facilitated the rapid development of HTS amenable assays to address cancer drug discovery in 3D tissues such as organoids and spheroids;
7020-437: The theory of discontinuous automatic control, which became widely used in hysteresis control systems such as navigation systems , fire-control systems , and electronics . Through Flugge-Lotz and others, the modern era saw time-domain design for nonlinear systems (1961), navigation (1960), optimal control and estimation theory (1962), nonlinear control theory (1969), digital control and filtering theory (1974), and
7110-488: The theory of discontinuous automatic controls, which found military applications during the Second World War to fire control systems and aircraft navigation systems . Controllers, which were able to make calculated changes in response to deviations from a set point rather than on-off control, began being introduced in the 1930s. Controllers allowed manufacturing to continue showing productivity gains to offset
7200-713: The time being, not all tasks can be automated, and some tasks are more expensive to automate than others. Initial costs of installing the machinery in factory settings are high, and failure to maintain a system could result in the loss of the product itself. Moreover, some studies seem to indicate that industrial automation could impose ill effects beyond operational concerns, including worker displacement due to systemic loss of employment and compounded environmental damage; however, these findings are both convoluted and controversial in nature, and could potentially be circumvented. The main advantages of automation are: Automation primarily describes machines replacing human action, but it
7290-556: The transition to a more automated future need not inspire panic, if there is sufficient political will to promote the retraining of workers whose positions are being rendered obsolete. According to a 2020 study in the Journal of Political Economy , automation has robust negative effects on employment and wages: "One more robot per thousand workers reduces the employment-to-population ratio by 0.2 percentage points and wages by 0.42%." Research by Carl Benedikt Frey and Michael Osborne of
7380-526: The use of humans is more cost-effective than mechanical approaches even where the automation of industrial tasks is possible. Therefore, algorithmic management as the digital rationalization of human labor instead of its substitution has emerged as an alternative technological strategy. Overcoming these obstacles is a theorized path to post-scarcity economics. Increased automation often causes workers to feel anxious about losing their jobs as technology renders their skills or experience unnecessary. Early in
7470-494: The use of various equipment and control systems such as machinery , processes in factories , boilers , and heat-treating ovens , switching on telephone networks , steering , stabilization of ships , aircraft and other applications and vehicles with reduced human intervention. Examples range from a household thermostat controlling a boiler to a large industrial control system with tens of thousands of input measurements and output control signals. Automation has also found
7560-478: The weight of the vehicle, and coupled with more precise acceleration and braking, as well as fuel-efficient route mapping, can increase fuel economy and reduce emissions. Despite this, some researchers theorize that an increase in the production of self-driving cars could lead to a boom in vehicle ownership and usage, which could potentially negate any environmental benefits of self-driving cars if they are used more frequently. Automation of homes and home appliances
7650-415: The wells of a stock plate to the corresponding wells of a completely empty plate. To prepare for an assay , the researcher fills each well of the plate with some biological entity that they wish to conduct the experiment upon, such as a protein , cells , or an animal embryo . After some incubation time has passed to allow the biological matter to absorb, bind to, or otherwise react (or fail to react) with
7740-541: The world can take advantage of this facility without lengthy intellectual property negotiations. With a compound library of over 200,000 small molecules, the MSSR has one of the largest compound deck of all universities on the west coast. Also, the MSSR features full functional genomics capabilities (genome wide siRNA, shRNA, cDNA and CRISPR) which are complementary to small molecule efforts: Functional genomics leverages HTS capabilities to execute genome wide screens which examine
7830-628: Was Air France Flight 447 , where a failure of automation put the pilots into a manual situation they were not prepared for. Many roles for humans in industrial processes presently lie beyond the scope of automation. Human-level pattern recognition , language comprehension , and language production ability are well beyond the capabilities of modern mechanical and computer systems (but see Watson computer ). Tasks requiring subjective assessment or synthesis of complex sensory data, such as scents and sounds, as well as high-level tasks such as strategic planning, currently require human expertise. In many cases,
7920-405: Was a tendency for oscillation whenever there was a speed change. As a consequence, engines equipped with this governor were not suitable for operations requiring constant speed, such as cotton spinning. Several improvements to the governor, plus improvements to valve cut-off timing on the steam engine, made the engine suitable for most industrial uses before the end of the 19th century. Advances in
8010-399: Was adopted by James Watt for use on a steam engine in 1788 after Watt's partner Boulton saw one at a flour mill Boulton & Watt were building. The governor could not actually hold a set speed; the engine would assume a new constant speed in response to load changes. The governor was able to handle smaller variations such as those caused by fluctuating heat load to the boiler. Also, there
8100-549: Was on a paper machine in 1919. One of the most important developments in the steel industry during the 20th century was continuous wide strip rolling, developed by Armco in 1928. Before automation, many chemicals were made in batches. In 1930, with the widespread use of instruments and the emerging use of controllers, the founder of Dow Chemical Co. was advocating continuous production . Self-acting machine tools that displaced hand dexterity so they could be operated by boys and unskilled laborers were developed by James Nasmyth in
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