Editing Nanorobotics (section)

==Approaches to manufacturing ==

Manufacturing nanomachines assembled from molecular components is a very challenging task. Because of the level of difficulty, many engineers and scientists continue working cooperatively across multidisciplinary approaches to achieve breakthroughs in this new area of development. The following techniques are currently applied towards manufacturing nanorobots:

===Biochip===
{{Main|Biochip}}
The joint use of [[nanoelectronics]], [[photolithography]], and new [[biomaterial]]s provides an approach to manufacturing nanorobots for common medical uses, such as surgical instrumentation, diagnosis, and drug delivery.<ref>{{cite journal |author=Fisher, B. |title=Biological Research in the Evolution of Cancer Surgery: A Personal Perspective |journal= Cancer Research |volume=68 |issue=24 |pages=10007–10020 |date=2008 |doi=10.1158/0008-5472.CAN-08-0186 |pmid=19074862|doi-access=free }}</ref><ref>{{Cite journal |doi= 10.3390/s8052932 |pmid= 27879858 |pmc= 3675524 |title= Nanorobot Hardware Architecture for Medical Defense |journal= Sensors |volume= 8 |issue= 5 |pages= 2932–2958 |year= 2008 |last1= Cavalcanti |first1= A. |last2= Shirinzadeh |first2= B. |last3= Zhang |first3= M. |last4= Kretly |first4= L. C.|bibcode= 2008Senso...8.2932C |doi-access= free }}</ref><ref>{{Cite journal |doi= 10.1586/14737140.8.12.1891 |title= Nano- and microrobotics: How far is the reality? |journal= Expert Review of Anticancer Therapy |volume= 8 |issue= 12 |pages= 1891–1897 |year= 2008 |last1= Hill |first1= C. |last2= Amodeo |first2= A. |last3= Joseph |first3= J. V. |last4= Patel |first4= H. R. |pmid=19046109|s2cid= 29688647 }}</ref> This method for manufacturing on nanotechnology scale is in use in the electronics industry since 2008.<ref>{{Cite journal |doi= 10.1080/00986440801930302 |title= Three-Dimensional Integration in Microelectronics: Motivation, Processing, and Thermomechanical Modeling |journal= Chemical Engineering Communications |volume= 195 |issue= 8 |pages= 847–888 |year= 2008 |last1= Cale |first1= T. S. |last2= Lu |first2= J. Q. |last3= Gutmann |first3= R. J.|s2cid= 95022083 }}</ref> So, practical nanorobots should be integrated as nanoelectronics devices, which will allow tele-operation and advanced capabilities for medical instrumentation.<ref>{{cite journal |author=Couvreur, P. |author2= Vauthier, C. |title=Nanotechnology: Intelligent Design to Treat Complex Disease |journal= Pharmaceutical Research |volume=23 |issue=7 |pages=1417–1450 |date=2006 |doi=10.1007/s11095-006-0284-8 |pmid=16779701|s2cid= 1520698 |doi-access=free }}</ref><ref>{{Cite journal |doi= 10.1227/01.neu.0000333820.33143.0d |title= The Future of Cerebral Surgery |journal= Neurosurgery |volume= 62 |issue= 6 Suppl 3 |pages= 1555–79; discussion 1579–82 |year= 2008 |last1= Elder |first1= J. B. |last2= Hoh |first2= D. J. |last3= Oh |first3= B. C. |last4= Heller |first4= A. C. |last5= Liu |first5= C. Y. |last6= Apuzzo |first6= M. L. J. |pmid=18695575}}</ref>

===Nubots===
{{Main|DNA machine}}

A ''nucleic acid robot'' (nubot) is an organic molecular machine at the nanoscale.<ref>{{Cite journal |doi= 10.1145/602421.602426 |title= Organic data memory using the DNA approach |journal= Communications of the ACM |volume= 46 |pages= 95–98 |year= 2003 |last1= Wong |first1= P. C. |last2= Wong |first2= K. K. |last3= Foote |first3= H.|citeseerx= 10.1.1.302.6363 |s2cid= 15443572 }}</ref> DNA structure can provide means to assemble 2D and 3D nanomechanical devices. DNA based machines can be activated using small molecules, proteins and other molecules of DNA.<ref>{{cite journal |author=Seeman. N. C. |title=From genes to machines: DNA nanomechanical devices |journal= Trends in Biochemical Sciences |volume=30 |issue=3 |pages=119–125 |date=2005 |doi=10.1016/j.tibs.2005.01.007|pmid=15752983 |pmc=3471994}}</ref><ref>{{cite journal |author=Montemagno, C. |author2= Bachand, G. |title=Constructing nanomechanical devices powered by biomolecular motors |journal= Nanotechnology |volume=10 |issue=3 |pages=225–231 |date=1999 |doi=10.1088/0957-4484/10/3/301|bibcode=1999Nanot..10..225M|s2cid= 250910730 }}</ref><ref>{{Cite journal |doi= 10.1038/nature06451 |title= Programming biomolecular self-assembly pathways |journal= Nature |volume= 451 |issue= 7176 |pages= 318–322 |year= 2008 |last1= Yin |first1= P. |last2= Choi |first2= H. M. T. |last3= Calvert |first3= C. R. |last4= Pierce |first4= N. A. |pmid=18202654|bibcode= 2008Natur.451..318Y |s2cid= 4354536 |url= https://resolver.caltech.edu/CaltechAUTHORS:20170224-143742507 }}</ref> Biological circuit gates based on DNA materials have been engineered as molecular machines to allow in-vitro drug delivery for targeted health problems.<ref>{{Cite journal |last1= Douglas |first1= Shawn M. |last2= Bachelet |first2= Ido |last3= Church |first3= George M. |doi= 10.1126/science.1214081 |title= A logic-gated nanorobot for targeted transport of molecular payloads |journal= Science |volume= 335 |issue= 6070 |pages= 831–834 |date= 17 February 2012 |pmid= 22344439|bibcode= 2012Sci...335..831D |s2cid= 9866509 }}</ref> Such material based systems would work most closely to smart biomaterial drug system delivery,<ref>{{cite journal |author=Jin, S. |author2= Ye, K. |title= Nanoparticle-Mediated Drug Delivery and Gene Therapy |journal= Biotechnology Progress |volume=23 |issue=1 |pages=32–41 |date=2007 |doi=10.1021/bp060348j|pmid= 17269667|s2cid= 9647481 }}</ref> while not allowing precise in vivo teleoperation of such engineered prototypes.

===Surface-bound systems===
Several reports show the attachment of [[synthetic molecular motor]]s to surfaces.<ref>{{Cite journal |doi= 10.1002/chem.200305712 |pmid= 15112199 |title= Powering Nanodevices with Biomolecular Motors |journal= Chemistry: A European Journal |volume= 10 | issue = 9  |pages= 2110–2116 |year= 2004 |last1= Hess |first1= Henry |last2= Bachand |first2= George D. |last3= Vogel |first3= Viola}}</ref><ref>{{Cite journal |doi= 10.1021/nn102876j |title= Adhesion of Photon-Driven Molecular Motors to Surfacesvia1,3-Dipolar Cycloadditions: Effect of Interfacial Interactions on Molecular Motion |journal= ACS Nano |volume= 5 |issue= 1 |pages= 622–630 |year= 2011 |last1= Carroll |first1= G. T. |last2= London |first2= G. B. |last3= Landaluce |first3= T. F. N. |last4= Rudolf |first4= P. |last5= Feringa |first5= B. L. |pmid=21207983|s2cid= 39105918 |url= https://pure.rug.nl/ws/files/6757528/2011ACSNanoCarroll.pdf }}</ref> These primitive nanomachines have been shown to undergo machine-like motions when confined to the surface of a macroscopic material. The surface anchored motors could potentially be used to move and position nanoscale materials on a surface in the manner of a conveyor belt.

===Positional nanoassembly===
Nanofactory Collaboration,<ref>[http://www.MolecularAssembler.com/Nanofactory "Nanofactory Collaboration"]. ''molecularassembler.com''.</ref> founded by [[Robert Freitas]] and [[Ralph Merkle]] in 2000 and involving 23 researchers from 10 organizations and 4 countries, focuses on developing a practical research agenda<ref>[http://www.MolecularAssembler.com/Nanofactory/Challenges.htm "Nanofactory Technical Challenges"]. ''molecularassembler.com''.</ref> specifically aimed at developing positionally-controlled diamond [[mechanosynthesis]] and a [[diamondoid]] nanofactory that would have the capability of building diamondoid medical nanorobots.

===Biohybrids===
{{see also|Biohybrid microswimmer}}

The emerging field of bio-hybrid systems combines biological and synthetic structural elements for biomedical or robotic applications. The constituent elements of bio-nanoelectromechanical systems (BioNEMS) are of nanoscale size, for example DNA, proteins or nanostructured mechanical parts. Thiol-ene e-beams resist allow the direct writing of nanoscale features, followed by the functionalization of the natively reactive resist surface with biomolecules.<ref>{{Cite journal|last1=Shafagh|first1=Reza|last2=Vastesson|first2=Alexander|last3=Guo|first3=Weijin|last4=van der Wijngaart|first4=Wouter|last5=Haraldsson|first5=Tommy|year=2018|title=E-Beam Nanostructuring and Direct Click Biofunctionalization of Thiol–Ene Resist|journal=ACS Nano|volume=12|issue=10|pages=9940–9946|language=en|doi=10.1021/acsnano.8b03709|pmid=30212184|s2cid=52271550|url=http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-236089}}</ref> Other approaches use a biodegradable material attached to magnetic particles that allow them to be guided around the body.<ref name="Yan Zhou Vincent Deng 2017 p.">{{cite journal | last1=Yan | first1=Xiaohui | last2=Zhou | first2=Qi | last3=Vincent | first3=Melissa | last4=Deng | first4=Yan | last5=Yu | first5=Jiangfan | last6=Xu | first6=Jianbin | last7=Xu | first7=Tiantian | last8=Tang | first8=Tao | last9=Bian | first9=Liming | last10=Wang | first10=Yi-Xiang J. | last11=Kostarelos | first11=Kostas | last12=Zhang | first12=Li | title=Multifunctional biohybrid magnetite microrobots for imaging-guided therapy | journal=Science Robotics | publisher=American Association for the Advancement of Science (AAAS) | volume=2 | issue=12 | date=2017-11-22 | issn=2470-9476 | doi=10.1126/scirobotics.aaq1155| pmid=33157904 | s2cid=2931559 | doi-access=free }}</ref>

===Bacteria-based===
{{see also|Bacterial motility}}

This approach uses biological microorganisms, like the [[bacterium]] ''[[Escherichia coli]]''<ref>{{Cite journal |doi= 10.1177/0278364908100924 |title= Flagellated Magnetotactic Bacteria as Controlled MRI-trackable Propulsion and Steering Systems for Medical Nanorobots Operating in the Human Microvasculature |journal= The International Journal of Robotics Research |volume= 28 |issue= 4 |pages= 571–582 |year= 2009 |last1= Martel |first1= S. |last2= Mohammadi |first2= M. |last3= Felfoul |first3= O. |last4= Zhao Lu |last5= Pouponneau |first5= P. |pmid=19890435 |pmc=2772069}}</ref> and ''[[Salmonella typhimurium]]''.<ref>{{Cite journal |doi= 10.1038/srep03394 |title= New paradigm for tumor theranostic methodology using bacteria-based microrobot |journal= Scientific Reports |volume= 3 |pmid= 24292152 |year= 2013 |last1= Park |first1= Sung Jun |last2= Park |first2= Seung-Hwan |last3= Cho |first3= S. |last4= Kim |first4= D. |last5= Lee |first5= Y. |last6= Ko |first6= S. |last7= Hong |first7= Y. |last8= Choy |first8= H. |last9= Min |first9= J. |last10= Park |first10= J. |last11= Park |first11= S. |pmc=3844944 |pages=3394|bibcode= 2013NatSR...3.3394P }}</ref> Thus the model uses a flagellum for propulsion purposes. Electromagnetic fields normally control the motion of this kind of biological integrated device.<ref>{{Cite thesis |last=Sakar |first=Mahmud |date=22 November 2010 |title=MicroBioRobots for Single Cell Manipulation |url=https://repository.upenn.edu/handle/20.500.14332/29799 |format=PDF |type=Doctor of Philosophy (PhD) |location=Philadelphia |publisher=University of Pennsylvania |access-date=21 April 2024}}</ref> Chemists at the University of Nebraska have created a humidity gauge by fusing a bacterium to a silicon computer chip.<ref>{{cite journal |author=Berry, V.|author2=Saraf, R. F. |title=Self-assembly of nanoparticles on live bacterium: An avenue to fabricate electronic devices |journal=Angewandte Chemie International Edition |volume=44 |issue=41 |pages=6668–6673 |date=2005 |doi=10.1002/anie.200501711 |pmid=16215974|s2cid= 15662656 |url= https://digitalcommons.unl.edu/cbmesaraf/11 |doi-access=free }}</ref>

===Virus-based===
[[Retrovirus]]es can be used to attach to [[cell (biology)|cell]]s and replace [[DNA]]. They go through a process called [[reverse transcription]] to deliver [[gene]]tic packaging in a [[vector (molecular biology)|vector]].<ref>RCSB Protein Data Bank. [http://www.rcsb.org/pdb/101/motm.do?momID=33 "RCSB PDB-101"] {{Webarchive|url=https://web.archive.org/web/20151019150835/http://www.rcsb.org/pdb/101/motm.do?momID=33 |date=2015-10-19 }}. ''rcsb.org''.</ref> Usually, these devices are Pol – Gag [[gene]]s of the [[virus]] for the [[Capsid]] and Delivery system. This process is called [[retroviral]] [[gene therapy]], having the ability to re-engineer [[cell (biology)|cellular]] [[DNA]] by usage of [[Virus|viral]] [[vector (molecular biology)|vectors]].<ref>Perkel, Jeffrey M.  [http://www.sciencemag.org/site/products/posters/GeneDeliveryPoster.PDF Viral Mediated Gene Delivery].  sciencemag.org</ref> This approach has appeared in the form of [[Retrovirus|retroviral]], [[Adenoviridae|adenoviral]], and [[Lentivirus|lentiviral]] [[gene]] delivery systems.<ref>{{Cite journal |last1=Cepko |first1=C. |last2=Pear |first2=W. |date=2001 |orig-date=October 1996 |title=Overview of the Retrovirus Transduction System |journal=Current Protocols in Molecular Biology |volume=Chapter 9 |at=Unit9.9 |doi=10.1002/0471142727.mb0909s36 |isbn=978-0471142720 |pmid=18265289 |s2cid=30240008}}</ref><ref name="CepkoPear2001">{{cite journal|last1=Cepko|first1=Constance|last2=Pear|first2=Warren|title=Overview of the Retrovirus Transduction System|journal=Current Protocols in Molecular Biology|volume=36 |pages=9.9.1–9.9.16 |year=2001|issn=1934-3639|doi=10.1002/0471142727.mb0909s36|pmid=18265289|s2cid=30240008}}</ref> These gene therapy vectors have been used in cats to send genes into the [[genetically modified organism]] (GMO), causing it to display the trait.<ref>{{cite news |last=Jha |first=Alok |url=https://www.theguardian.com/science/2011/sep/11/genetically-modified-glowing-cats |title=Glow cat: fluorescent green felines could help study of HIV |work=The Guardian |date=11 September 2011}}</ref>