Editing Laboratory robotics (section)

==Applications==

=== Low-cost laboratory robotics ===
[[File:Low-cost robotic arm employed as an autosampler.jpg|alt=Low-cost robotic arm used as an autosampler.|thumb|Low-cost robotic arm used as an autosampler.]]
The high cost of many laboratory robots has inhibited their adoption. However, currently there are many robotic devices that have very low cost, and these could be employed to do some jobs in a laboratory. For example, a low-cost robotic arm was employed to perform several different kinds of water analysis, without loss of performance compared to much more expensive autosamplers.<ref>{{Cite journal|last1=Carvalho|first1=Matheus C.|last2=Eyre|first2=Bradley D.|date=2013-12-01|title=A low cost, easy to build, portable, and universal autosampler for liquids|journal=Methods in Oceanography|volume=8|pages=23–32|doi=10.1016/j.mio.2014.06.001|bibcode=2013MetOc...8...23C }}</ref> Alternatively, the autosampler of a device can be used with another device,<ref name=":2" /> thus avoiding the need for purchasing a different autosampler or hiring a technician for doing the job. The key aspects to achieve low-cost in laboratory robotics are 1) the use of low-cost robots, which become more and more common, and 2) the use of scripting, which enables compatibility between robots and other analytical equipment.<ref>{{Cite book|title=Practical Laboratory Automation: Made Easy with AutoIt.|last=Carvalho|first=Matheus|publisher=Wiley VCH|year=2017}}</ref>

=== Robotic, mobile laboratory operators and remote-controlled laboratories ===
In July 2020 scientists reported the development of a mobile robot chemist and demonstrate that it can assist in experimental searches. According to the scientists their strategy was [[Laboratory automation|automating]] the researcher rather than the instruments – freeing up time for the human researchers to think creatively – and could identify photocatalyst mixtures for hydrogen production from water that were six times more active than initial formulations. The modular robot can operate laboratory instruments, work nearly around the clock, and autonomously make decisions on his next actions depending on experimental results.<ref>{{cite news |title=Researchers build robot scientist that has already discovered a new catalyst |url=https://phys.org/news/2020-07-robot-scientist-catalyst.html |access-date=16 August 2020 |work=phys.org |language=en}}</ref><ref>{{cite journal |last1=Burger |first1=Benjamin |last2=Maffettone |first2=Phillip M. |last3=Gusev |first3=Vladimir V. |last4=Aitchison |first4=Catherine M. |last5=Bai |first5=Yang |last6=Wang |first6=Xiaoyan |last7=Li |first7=Xiaobo |last8=Alston |first8=Ben M. |last9=Li |first9=Buyi |last10=Clowes |first10=Rob |last11=Rankin |first11=Nicola |last12=Harris |first12=Brandon |last13=Sprick |first13=Reiner Sebastian |last14=Cooper |first14=Andrew I. |title=A mobile robotic chemist |journal=Nature |date=July 2020 |volume=583 |issue=7815 |pages=237–241 |doi=10.1038/s41586-020-2442-2 |pmid=32641813 |bibcode=2020Natur.583..237B |s2cid=256820162 |url=https://strathprints.strath.ac.uk/74759/1/Burger_etal_Nature_2020_A_mobile_robotic.pdf |access-date=16 August 2020 |language=en |issn=1476-4687}}</ref>

There is ongoing development of "remote controlled laboratories" that automatically perform many life sciences experiments per day and can be operated, including in collaboration, from afar.<ref>{{cite web |title=Robots Get Ready to Roam in Clinical Labs {{!}} AACC.org |url=https://www.aacc.org/cln/articles/2020/october/robots-get-ready-to-roam-in-clinical-labs |website=www.aacc.org |date=October 2020 |access-date=25 May 2022}}</ref>

===Pharmaceutical applications===

One major area where automated synthesis has been applied is structure determination in [[pharmaceutical research]]. Processes such as [[NMR]] and [[HPLC]]-[[Mass spectrometry|MS]] can now have sample preparation done by robotic arm.<ref>Gary A. McClusky, Brian Tobias. "Automation of Structure Analysis in Pharmaceutical R&D." Journal of Management of Information Systems  (1996).</ref> Additionally, structural protein analysis can be done automatically using a combination of NMR and [[X-ray crystallography]]. [[Crystallization]] often takes hundreds to thousands of experiments to create a protein crystal suitable for X-ray crystallography.<ref>Heinemann, Udo, Gerd Illing, and Hartmut Oschkinat. "High-Throughput Three-Dimensional Protein Structure Determination." Current Opinion in Biotechnology 12.4 (2001): 348-54.</ref> An automated micropipet machine can allow nearly a million different crystals to be created at once, and analyzed via X-ray crystallography.

===Reproducibility verification===
{{Excerpt|Replication crisis|Semi-automated}}

=== Diagnostic testing for pathogens ===
{{See also|Medical diagnosis|Diagnostic robot}}
{{Expand section|date=May 2022}}
For example, there are robots that are used to analyze swabs from patients to [[COVID-19 testing|diagnose COVID-19]].<ref>{{cite news |last1=Sanders |first1=Robert |title=UC Berkeley scientists spin up a robotic COVID-19 testing lab |url=https://news.berkeley.edu/2020/03/30/uc-berkeley-scientists-spin-up-a-robotic-covid-19-testing-lab/ |access-date=25 May 2022 |work=Berkeley News |date=30 March 2020}}</ref><ref>{{cite web |title=Robot automates COVID-19 testing |url=https://healthcare-in-europe.com/en/news/robot-automates-covid-19-testing.html |website=healthcare-in-europe.com |access-date=25 May 2022 |language=en}}</ref><ref>{{cite web |title=CDC B-Roll {{!}} CDC Online Newsroom {{!}} CDC |url=https://www.cdc.gov/media/b_roll.html |website=www.cdc.gov |access-date=25 May 2022 |language=en-us |date=30 March 2022 |quote=This b-roll depicts the lab work involved in serology testing. This laboratory robot performs all the steps of the SARS-CoV-2 antibody test from sample loading through antibody detection in one workflow, and it can test over 3,600 samples a day. A public health scientist can test about 400 samples a day by hand. The use of automated laboratory robots will improve antibody testing capacity, resulting in more data to help monitor and respond to the COVID-19 pandemic.}}</ref> Automated robotic liquid handling systems have been or are being built for [[lateral flow assay]]s. It minimizes hands-on time, maximizes experiment size, and enables improved reproducibility.<ref>{{cite journal |last1=Anderson |first1=Caitlin E. |last2=Huynh |first2=Toan |last3=Gasperino |first3=David J. |last4=Alonzo |first4=Luis F. |last5=Cantera |first5=Jason L. |last6=Harston |first6=Stephen P. |last7=Hsieh |first7=Helen V. |last8=Marzan |first8=Rosemichelle |last9=McGuire |first9=Shawn K. |last10=Williford |first10=John R. |last11=Oncina |first11=Ciela I. |last12=Glukhova |first12=Veronika A. |last13=Bishop |first13=Joshua D. |last14=Cate |first14=David M. |last15=Grant |first15=Benjamin D. |last16=Nichols |first16=Kevin P. |last17=Weigl |first17=Bernhard H. |title=Automated liquid handling robot for rapid lateral flow assay development |journal=Analytical and Bioanalytical Chemistry |date=1 March 2022 |volume=414 |issue=8 |pages=2607–2618 |doi=10.1007/s00216-022-03897-9 |pmid=35091761 |pmc=8799445 |language=en |issn=1618-2650|doi-access=free }}</ref>

=== Biological laboratory robotics ===
[[File:Automated pipetting system using manual pipettes.jpg|thumb|right|An example of pipettes and microplates manipulated by an anthropomorphic robot (Andrew Alliance)]]
Biological and chemical samples, in either liquid or solid state, are stored in vials, plates or tubes. Often, they need to be frozen and/or sealed to avoid contamination or to retain their biological and/or chemical properties.  Specifically, the life science industry has standardized on a plate format, known as the [[microtiter plate]],<ref>{{Cite journal 
| last1 = Barsoum | first1 = I. S. 
| last2 = Awad | first2 = A. Y. 
| title = Microtiter plate agglutination test for Salmonella antibodies 
| journal = Applied Microbiology 
| volume = 23 
| issue = 2 
| pages = 425–426 
| year = 1972 
| doi = 10.1128/AEM.23.2.425-426.1972 
| pmid = 5017681 
| pmc = 380357
}}</ref> to store such samples.

The microtiter plate standard was formalized by the Society for Biomolecular Screening in 1996.<ref>"Microplate Standardization, Report 3"
submitted by T. Astle Journal of Biomolecular Screening (1996). Vol. 1 No. 4, pp 163-168.</ref>  It typically has 96, 384 or even 1536 sample wells arranged in a 2:3 rectangular matrix.  The standard governs well dimensions (e.g. diameter, spacing and depth) as well as plate properties (e.g. dimensions and rigidity).

A number of companies have developed robots to specifically handle SBS microplates.  Such robots may be liquid handlers which aspirates or dispenses liquid samples from and to these plates, or "plate movers" which transport them between instruments.

Other companies have pushed integration even further: on top of interfacing to the specific consumables used in biology, some robots (Andrew<ref>{{Citation 
  | title = hands-free use of pipettes
  | date = October 2012
  | url = http://www.andrewalliance.com
  | access-date = September 30, 2012}}</ref> by Andrew Alliance, see picture) have been designed with the capability of interfacing to volumetric pipettes used by biologists and technical staff. Essentially, all the manual activity of liquid handling can be performed automatically, allowing humans spending their time in more conceptual activities.

Instrument companies have designed [[plate reader]]s which can carry out detect specific biological, chemical or physical events in samples stored in these plates.  These readers typically use optical and/or [[computer vision]] techniques to evaluate the contents of the microtiter plate wells.

One of the first applications of robotics in biology was [[peptide]] and [[oligonucleotide synthesis]]. One early example is the [[polymerase chain reaction]] (PCR) which is able to amplify DNA strands using a [[thermal cycler]] to micromanage DNA synthesis by adjusting temperature using a pre-made computer program. Since then, automated synthesis has been applied to organic chemistry and expanded into three categories: '''reaction-block systems''', '''robot-arm systems''', and '''non-robotic fluidic systems'''.<ref>Nicholas W Hird [[Drug Discovery Today]], Volume 4, Issue 6, p.265-274 (1999) [https://dx.doi.org/10.1016/S1359-6446(99)01337-9]</ref> The primary objective of any automated workbench is high-throughput processes and cost reduction.<ref>David Cork, Tohru Sugawara. Laboratory Automation in the Chemical Industries. CRC Press, 2002.</ref> This allows a synthetic laboratory to operate with a fewer number of people working more efficiently.

===Combinatorial library synthesis===
Robotics have applications with [[combinatorial chemistry]] which has great impact on the [[pharmaceutical]] industry. The use of robotics has allowed for the use of much smaller reagent quantities and mass expansion of chemical libraries. The "parallel synthesis" method can be improved upon with automation. The main disadvantage to "parallel-synthesis" is the amount of time it takes to develop a library, automation is typically applied to make this process more efficient.

The main types of automation are classified by the type of solid-phase substrates, the methods for adding and removing reagents, and design of reaction chambers. Polymer resins may be used as a substrate for solid-phase.<ref>Hardin, J.; Smietana, F., Automating combinatorial chemistry: A primer on benchtop robotic systems. Mol Divers 1996, 1 (4), 270-274.</ref> It is not a true combinatorial method in the sense that ''"split-mix"'' where a peptide compound is split into different groups and reacted with different compounds. This is then mixed back together split into more groups and each groups is reacted with a different compound. Instead the "parallel-synthesis" method does not mix, but reacts different groups of the same peptide with different compounds and allows for the identification of the individual compound on each solid support.  A popular method implemented is the reaction block system due to its relative low cost and higher output of new compounds compared to other "parallel-synthesis" methods. Parallel-Synthesis was developed by ''Mario Geysen'' and his colleagues and is not a true type of combinatorial synthesis, but can be incorporated into a combinatorial synthesis.<ref>H. M. Geysen, R. H. Meloen, S. J. Barteling Proc. Natl. Acad. Sci. USA 1984, 81, 3998.</ref> This group synthesized 96 peptides on plastic pins coated with a solid support for the solid phase peptide synthesis. This method uses a rectangular block moved by a robot so that reagents can be pipetted by a robotic pipetting system. This block is separated into wells which the individual reactions take place. These compounds are later cleaved from the solid-phase of the well for further analysis. Another method is the closed reactor system which uses a completely closed off reaction vessel with a series of fixed connections to dispense. Though the produce fewer number of compounds than other methods, its main advantage is the control over the reagents and reaction conditions. Early closed reaction systems were developed for peptide synthesis which required variations in temperature and a diverse range of reagents. Some closed reactor system robots have a temperature range of 200°C and over 150 reagents.

===Purification===
Simulated distillation, a type of [[gas chromatography]] testing method used in the petroleum, can be automated via robotics. An older method used a system called ORCA (Optimized Robot for Chemical Analysis) was used for the analysis of petroleum samples by simulated distillation (SIMDIS). ORCA has allowed for shorter analysis times and has reduced maximum temperature needed to elute compounds.<ref>William F. Berry, V. G., Automated simulated distillation using an articulated laboratory robot system. Journal of Automatic Chemistry 1994, 16 (6), 205-209.</ref> One major advantage of automating purification is the scale at which separations can be done.<ref>Paegel, Brian M., Stephanie H. I. Yeung, and Richard A. Mathies. "Microchip Bioprocessor for Integrated Nanovolume Sample Purification and DNA Sequencing." Analytical chemistry 74.19 (2002): 5092-98.</ref> Using microprocessors, ion-exchange separation can be conducted on a nanoliter scale in a short period of time.

Robotics have been implemented in liquid-liquid extraction (LLE) to streamline the process of preparing biological samples using 96-well plates.<ref>Peng, S. X.; Branch, T. M.; King, S. L., Fully Automated 96-Well Liquid−Liquid Extraction for Analysis of Biological Samples by Liquid Chromatography with Tandem Mass Spectrometry. Analytical Chemistry 2000, 73 (3), 708-714.</ref> This is an alternative method to solid-phase extraction methods and protein precipitation, which has the advantage of being more reproducible and robotic assistance has made LLE comparable in speed to solid phase extraction. The robotics used for LLE can perform an entire extraction with quantities in the microliter scale and performing the extraction in as little as ten minutes.