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Since 1991 IMM has been conducting and catalyzing research on Atomically Precise Manufacturing.  This includes development pathways, designs of devices and investigation into technological, economic and ethical implications. 

IMM promotes the advancement of molecular manufacturing by funding direct research, and by presenting at meetings, seminars, and conferences.

2019

Tad Hogg contributed to the following Workshops:  Foresight Institute, “Healing the Planet: Atomic Precision for Clean Energy & Clean Air.”  The Lodge, Palo Alto, California.  April 27-28, 2019.  https://foresight.org/event/healing-the-planet-atomic-precision-for-clean-energy-clean-air/

Foresight Institute, “Contemporary Materials Science: How Can Molecular Machines Help?”  Northwestern University Campus.  September 20-21, 2019.  https://foresight.org/event/contemporary-materials-science-how-can-molecular-machines-help/

Stanford BIO-X Undergraduate Research Sessions.  Stanford University.  Summer 2019.  https://biox.stanford.edu/research/undergraduate-research

Neil Jacobstein: Gave multiple talks on AI and Robotics to worldwide industry audiences. All of these talks included a section on nanotechnology and atomically precise manufacturing.  Gave multiple talks on AI and Robotics for Singularity University’s Executive Seminars. All of these talks included a section on nanotechnology and atomically precise manufacturing.  Participated in several Seminars for Stanford University’s MediaX Program. These seminars included a section on nanotechnology and atomically precise manufacturing.  Participated in several Meetings with the US National Academy of Sciences Earth and Life Studies Committee. These meetings included discussions on nanotechnology and atomically precise manufacturing.  Designed and moderated a very successful day long AI seminar for Aspen Institute New Zealand, which included education on molecular robotics and atomically precise manufacturing.

Paul Melnyk represented IMM at Foresight Institute’s, “Eric Drexler, Robin Hanson, Mark S. Miller: Decentralized Approaches to Artificial Intelligence.”  Academia.edu, San Francisco, California.  May 17, 2019.  https://foresight.org/event/eric-drexler-robin-hanson-mark-s-miller-decentralized-approaches-to-artificial-intelligence/

2018

Jacobstein gave over 20 talks worldwide in 2018 on Exponential Technology, AI and Robotics for Singularity University. His talks always included a section on Atomically Precise Manufacturing as a subset of the Robotics topic. One of them on Jan 19, 2018 in Munich Germany highlighted a Science article on a self assembled nanoscale robotic arm published on Jan 18, 2018. A talk in China in June 2018 highlighted the discovery of an organic molecule on Mars by the Curiosity Rover, and made the point that we are driving our intelligence into remote robotics.

Jacobstein wrote most of the AI section of this frequently downloaded article, and he has regularly encouraged the Science Robotics Editorial team to regard Atomically Precise Manufacturing as a subset of Robotics.

In 2018, Jacobstein was reappointed a Distinguished Visiting Scholar at Stanford, and gave 4 talks for Stanford University in Brazil and Palo Alto on Exponential Technology, AI and Robotics. His talks always included a section on Atomically Precise Manufacturing as a subset of the Robotics topic.

Jacobstein was reappointed to the Editorial Board of the AAAS Journal Science Robotics for the 2018 year.

Jacobstein gave over 10 media interviews in 2018 on Exponential Technology, AI, and Robotics. His interviews always included comments on the significance of Atomically Precise Manufacturing.

Newly appointed IMM Senior Research Fellow Ted Kaehler began to create a series of web pages.  The pages explore paths to creating the first Atomically Precise Manufacturing prototype.  There are many potential paths and supporting technologies, and the pages will discuss the advantages and difficulties of the most promising ones. The goal is to inspire research in areas that need to be developed for the first examples of Atomically Precise Manufacturing.

Jacobstein encouraged Ted Kaehler’s involvement in IMM, and his long term nanotech pathways project while Paul Melnyk assisted in project development.

Paul Melnyk represented IMM at “Medicine & Due Diligence” in September 2018, Family Life Center, Los Gatos, California.  Keynote speaker, Dr. Promod Haque, Senior Managing Partner at Norwest Venture Partners.  Presentation by Dr. Samuel Perli, Postdoctoral Fellow working with Prof. Shinya Yamanaka, the 2012 Nobel Laureate in Physiology or Medicine, at Gladstone Institute and UCSF.

2017

Robert A. Freitas Jr., was featured in the article, “From Science Fiction to Medical Reality, Robert Freitas ’74 envisions the future benefits of nanorobotics, an emerging area of nanotechnology.” Harvey Mudd College Magazine, Summer 2017.Written by Amy Derbedrosian; https://magazine.hmc.edu/summer-2017/science-fiction-medical-reality/

Neil Jacobstein was reappointed in 2017 to a second three year term at the National Academy of Sciences, Engineering and Medicine’s Earth and Life Studies Committee 2018-2021. He often represents the atomically precise manufacturing perspective during the technical discussions of this committee in Washington DC.

Neil Jacobstein wrote most of the AI section of this frequently downloaded article, and he has regularly encouraged the Science Robotics Editorial team to regard Atomically Precise Manufacturing as a subset of Robotics.

Neil Jacobstein was reappointed to the Editorial Board of the AAAS Journal Science Robotics for the 2018 year.

Neil Jacobstein gave over 25 talks worldwide in 2017 on Exponential Technology, AI and Robotics for Singularity University. His talks always included a section on Atomically Precise Manufacturing as a subset of the Robotics topic.

In 2017, Neil Jacobstein was reappointed a Distinguished Visiting Scholar at Stanford, and gave 5 talks for Stanford University in Brazil and Palo Alto on Exponential Technology, AI and Robotics. His talks always included a section on Atomically Precise Manufacturing as a subset of the Robotics topic.

In 2017, Neil Jacobstein gave over a dozen talks worldwide for public speaking agencies on Exponential Technology, AI and Robotics for Singularity University. His talks always included a section on Atomically Precise Manufacturing as a subset of the Robotics topic.

Neil Jacobstein gave over 10 media interviews in 2017 on Exponential Technology, AI, and Robotics. His interviews always included comments on the significance of Atomically Precise Manufacturing.

Paul Melnyk presented a generalist’s overview of nanotechnology at a private event for Silicon Valley municipality and business leaders.  “Paul provided a fascinating look into the world of nanotechnology. He offered perspective on the history of exploration in this field and the manipulation of particles at the nanometre scale.”

2016

Neil Jacobstein joined the founding Editorial Board of AAAS Science Robotics in January 2016. This Science journal covers macro to nano scale robotics.

Guang-Zhong Yang, James Bellingham, Howie Choset, Paolo Dario, Peer Fischer, Toshio Fukuda, Neil Jacobstein, Bradley Nelson, Manuela Veloso and Jeremy Berg, “Science for Robotics and Robotics for Science,” Science Robotics 06 Dec 2016: Vol. 1, Issue 1, eaal2099, DOI: 10.1126/scirobotics.aal2099.

Neil Jacobstein, “Exponentials: AI and Machine Learning” Exponential Manufacturing, Westin Hotel, Boston, May 10, 2016. Sponsored by Deloitte, and Singularity University. https://exponential.singularityu.org/manufacturing/

Neil Jacobstein, “The Augmentation Imperative”, MediaX Conference on Augmenting Personal Intelligence, Stanford University, May 17, 2016. http://mediax.stanford.edu/events/mediax2016-conference.

Exponential Finance sponsored by CNBC, “Artificial Intelligence.” Conrad Hotel, New York, New York June 9, 2016. Sponsored by CNBC, Deloitte, and Singularity University. http://exponential.singularityu.org/finance/

Neil Jacobstein, “Artificial Intelligence, Business, and The Future of Work” Socrates Seminar, July 8-11, 2016. Aspen Institute, Aspen Colorado.

Neil Jacobstein, “The Artificial Intelligence Revolution”, Singularity University Global Summit, Hilton Hotel, San Francisco, September 28, 2016.

Neil Jacobstein, “Artificial Intelligence (Update on 2016 R&D).” Exponential Medicine Conference, Coronado Hotel, San Diego, CA., November 8, 2016. Sponsored by Singularity University.

2015

Neil Jacobstein, Department of Energy, “Integrated Nanosystems for Atomically Precise Manufacturing Workshop,” Jacobstein was an invited participant of a 28 person workshop on research priorities for atomically precise manufacturing, DoubleTree Hotel, Berkeley California August 5-6, 2015. Neil also recruited Dr. Eric Drexler, Oxford Martin Senior Fellow, Oxford Martin School for this workshop.

Neil Jacobstein addressed R&D issues in molecular manufacturing and fielded questions about potential risks during a series of lectures and workshops held in the US and Europe, sponsored by Singularity University. Members of Fortune 1000 global companies and governments were in attendance at several of these workshops.

Neil Jacobstein briefed the IC community on advanced robotics, including prospects for molecular robotics on March 23, 2015.

Paul Melnyk, master of ceremonies at the 2014 Feynman Prize Awards banquet in Palo Alto, California on April 23, 2015.

2014

Neil Jacobstein addressed R&D issues in molecular manufacturing and fielded questions about potential risks during a series of lectures and workshops held in the US and Europe, sponsored by Singularity University. Members of Fortune 1000 global companies and governments were in attendance at several of these workshops.

Neil Jacobstein briefed the Atlantic Council on advanced robotics, including prospects for molecular robotics and atomically precise manufacturing.

Paul Melnyk, master of ceremonies at the 2013 Feynman Prize Awards banquet in Palo Alto, California on January 23, 2014.

2013

J. Storrs Hall, Ph.D., Profiles of the Future, Newman Summer Symposium, Newman University, Wichita, KS; Artificial Responsibility, Beyond AI: Artificial Golem Intelligence, University of Western Bohemia, Plzen, Czech Republic.

Neil Jacobstein, Lecture and workshop discussions of the economic, ethical, technical, and environmental aspects of nanotechnology and atomically precise manufacturing in over a dozen executive seminars, and approximately 20 invited speaking engagements in the US, Argentina, Hungary, Holland, Denmark, Italy, England, and other countries. Several of the seminars were with C level executives from Fortune 1000 companies.

2012

Neil Jacobstein, Singularity University Seminar in Milan. “Artificial Intelligence”, May 2, 2012. [Included references to molecular robotics]

Neil Jacobstein, Keren Hayesod Foundation, Computer History Museum, Mountain View, CA, “Workshop on Ethics of Exponential Technologies.”, May 14, 2012.

Neil Jacobstein, SETI Institute Mountain View, California, SETICON II Panel. “What’s Next in Science?” June 22, 2012.

Neil Jacobstein, Singularity University at NASA Ames, Graduate Summer Program 2012, Workshop on the Ethics of Exponential Technologies.

2011

T. Hogg & Freitas developed and evaluated designs of acoustic communication for medical nanorobots

Neil Jacobstein, Stanford University, “Creative Disruption”, lecture for Media X Audience that referenced nanotechnology as one exponential technology that would cause disruption of current corporate and political systems. October, 19, 2011.

Neil Jacobstein, Singularity University at NASA Ames, Multiple Executive Programs, Workshop with Ralph Merkle on the Ethical Implications of Nanotechnology.

Neil Jacobstein, Singularity University at NASA Ames, Graduate Summer Program 2011, Workshop with Ralph Merkle on the Ethical Implications of Nanotechnology.

Neil Jacobstein, 4th ISPIM Innovation Symposium – Managing Innovation for Sustained Productivity: Creating Advantage and Resilience. Wellington, New Zealand. December 1, 2011. “Incremental and Transformational Innovation for Measurable Improvements in Knowledge Worker Productivity”. [included references to advanced nanotechnology]

2010

Robert A. Freitas Jr., Scenario Analysis using a Simple Econometric Model of Alcor Finances, Alcor Foundation, 15 October 2010.

Ralph C. Merkle, 2009 Feynman Lecture: Contributions of Robert Freitas to Molecular Nanotechnology, 2010 Foresight Conference on Nanotech and AI, Palo Alto CA, 16-17 January 2010.

Neil Jacobstein and Ralph Merkle collaborated on four 3 hour workshops on the Ethical Implications of Nanofactories. These were based on work began at IMM and presented for discussion and review at the non profit Singularity University in the NASA Ames Research Park.

2009

Neil Jacobstein and Ralph Merkle gave two workshops in 2009 on the Ethical Implications of Nanofactories, at Singularity University at NASA Ames.

Neil Jacobstein gave a one day seminar on Augmented Decision Environments, Oct 19, 2009 at Stanford University. This seminar included a briefing on the possibilities for using molecular manufacturing to address some of humanities grand challenges.

Neil Jacobstein provided nanotechnology background for vetting some solar technology candidates for the Aspen Institute’s Energy and Environment Awards.

Neil Jacobstein wrote a chapter on Nanotechnology in: “Fighting Chance: Global Trends and Shocks in the National Security Environment”, Edited by Neyla Arnas, National Defense University Press and Potomac Books, 2009.

Ralph Merkle and Robert Freitas made a presentation at a life extension conference that has led, along with the efforts of others, to the formation of a company to pursue a variety of life extension technologies, including medical nanorobotics. The talk was titled:

Robert A. Freitas Jr., Ralph C. Merkle, Nanomedicine, Manhattan Beach Project Summit, Manhattan Beach, California, 13-15 November 2009. http://www.youtube.com/watch?v=T4ILDPiMs3M&feature=PlayList&p=588FEE45FE5B5D60&playnext=1&playnext_from=PL&index=50

Robert A. Freitas Jr. received the 2009 Feynman Prize in nanotechnology for theory (http://www.foresight.org/about/2009Feynman.html#2009Winners), in part for his work at IMM.

2008

D. R. Forrest, “Technology Roadmap for Productive Nanosystems,” Nanomanufacturing Conference and Exhibits, Society for Manufacturing Engineers, Framingham, MA, 22-23 April 2008.

2007

Robert A Freitas, Jr. won the 2007 Foresight Prize in Communication.

D.R. Forrest and N. Jacobstein, “Low Cost, Atomically-Precise Manufacturing of Defense Systems: Progress and Applications,” presented at the Society of Manufacturing Engineers conference Productive Nanosystems: Launching the Technology Roadmap, DoubleTree Hotel Crystal City, Arlington, VA , 9-10 October 2007.

David Forrest, Robert Freitas, and Neil Jacobstein provided substantial contributions to the International Technology Roadmap for Productive Nanosystems with three Working Group Proceedings: Molecular Machine Pathways, Diamondoid Mechanosynthesis, and Near-Term Applications. In addition, they provided editing assistance on the Fabrication section.

Neil Jacobstein discussed molecular nanotechnology at the “Robust Futures Workshop” in the Reuters Digital Vision Program, Stanford University, March 9, 2007. This workshop got rave reviews from participants.

David Forrest presented a talk on “Molecular Nanotechnology and the National Defense” at the Institute for Defense Analyses, 19 January 2007.

2006

Neil Jacobstein gave a talk on “Nanotechnology and Naval Energy R&D” at the Office of Naval Research sponsored Naval Science &Technology Partnership Conference: 2006, August 2, 2006.

Neil Jacobstein, “Foresight Guidelines,” April 2006.

Presentation: Forrest, D. R., “Transport Phenomena in Nanomechanical Systems for Molecular Manufacturing,” presented at the 2006 TMS Fall Extraction & Processing Meeting: Sohn International Symposium, San Diego, CA, 27-31 August 2006.

As a member of the Working Group for the Battelle/Foresight International Technology Roadmap for Productive Nanosystems, David Forrest presented a talk on “A Perspective on Approaches and Pathways to Productive Nanosystems” on March 20th at Oak Ridge National Laboratory, Oak Ridge, TN.

Robert Freitas presented an invited lecture, “Nanomedicine and Medical Nanorobotics: The Path Forward,” at the Sixth Alcor Conference: An Inside Look at the Science and Medicine of Tomorrow, 7 October 2006, Scottsdale, AZ.

Robert Freitas and Ralph Merkle co-founded the Nanofactory Collaboration. This group facilitates alliances with researchers on projects that advance the development of molecular manufacturing systems.

2005

IMM contributed two presentations on molecular manufacturing at the “Workshop on Molecular Self-Assembly for Manufacturing of Materials and Devices at the Molecular Scale,” held 9-11 February 2005 at the National Research Council, Washington, DC.

Neil Jacobstein gave a Keynote Talk on “The Future of Bits and Molecules” at the Annual Investors Meeting of Levensohn Venture Partners in May 2005.

Neil Jacobstein discussed molecular nanotechnology and the Foresight Guidelines at an Aspen Institute Socrates Seminar that he moderated on “Future Perspectives” July 2-4, 2005.

Neil Jacobstein provided a presentation on the feasibility and ethics of molecular manufacturing, to the New Zealand Ministry of Science and Technology in Wellington, NZ.

Neil Jacobstein presented a talk entitled, “Foresight Guidelines Update: Traction, Feedback, and Draft Version 5.0” at the Foresight Vision Weekend, 23 October 2005.

David Forrest and Josh Hall participated in a debate “Nanotechnology: Radical New Science or Plus Ça Change?,” U. of Nottingham Surface Science Summer School, Nottingham, UK, 24 August 2005. A transcript of the debate and streaming video are available. Forrest posted post-debate comments and you will also find comments from Richard Jones on his blog.

David Forrest presented a talk entitled: “Progress in Molecular Manufacturing,” (both slides and audio available from this link), Advancing Beneficial Nanotechnology: Focusing on the Cutting Edge, 13th Foresight Conference on Advanced Nanotechnology, San Francisco, 22-27 October 2005.

In 2005 Dr. Forrest prepared a white paper entitled “Molecular Manufacturing Will Change Materials Technology” for the Advisory Technical Awareness Council, the technology “look-ahead” arm of ASM International. The paper assesses the state of the art in progress on molecular manufacturing and provides recommendations to the society.

Neil Jacobstein reviewed and provided comments to Ralph Merkle and Robert Freitas on their book on Kinematic Self Replicating Machines.

David Forrest presented an invited talk for the Society for Manufacturing Engineers at their emerging technology forum in Minneapolis, 4 May 2005.

2004

Robert Freitas submitted the first patent ever filed on diamond mechanosynthesis:
Robert A. Freitas Jr., “A Simple Tool for Positional Diamond Mechanosynthesis, and its Method of Manufacture,” U.S. Provisional Patent Application No. 60/543,802, filed 11 February 2004; U.S. Patent Pending, 11 February 2005.

Robert Freitas gave an invited lecture, “Pathway to Diamond-Based Molecular Manufacturing,” at the First Symposium on Molecular Machine Systems at the First Foresight Conference on Advanced Nanotechnology, 22 October 2004, Washington, DC.

Robert Freitas gave an invited lecture, “Nanomedicine and Medical Nanorobotics,” at the First Foresight Conference on Advanced Nanotechnology, 23 October 2004, Washington, DC.

Robert Freitas and Ralph Merkle co-authored the technical book Kinematic Self-Replicating Machines (Landes
Bioscience, 2004), a landmark survey of the theoretical and experimental literature pertaining to physical self-replicating systems and self-replication.

Neil Jacobstein gave a keynote talk on: “Nanotechnology and Molecular Manufacturing” at the 11,000 member American Association of Clinical Chemistry Oak Ridge Conference, April 30, 2004.

Neil Jacobstein gave a keynote talk on: “Inventing the Future of Nanotechnology” for a monthly Forum of executives at the Greenwich Connecticut Country Club, March 25, 2004.

Neil Jacobstein made recommendations to the National Academy of Sciences on their upcoming panels and studies on the feasibility of nanotechnology, Spring/Summer, 2004.

Neil Jacobstein gave a talk on “The Strategic Significance of Nanotechnology and Molecular Manufacturing” at the Foresight Senior Associates Gathering, May 16, 2004.

Neil Jacobstein gave a briefing on “Nanotechnology and Molecular Manufacturing” to a group of officers and faculty at the National Security Forum, Maxwell Air Force Base, May 27, 2004.

Neil Jacobstein created and moderated a three-day Aspen Institute Socrates Seminar on “Future Scenarios: Tunneling Through the Uncertainty Barrier”, July 2-5, 2004. The seminar dealt with the need to anticipate the possibility, probability, and potential impacts of powerful new technologies, including molecular nanotechnology and manufacturing.

David Forrest presented the keynote address, “Molecular Manufacturing for Clean, Low Cost Textile Production,” at Ecotextile 04 in Manchester, UK, on July 7, 2004. He also prepared a corresponding paper on the same subject.

David Forrest, “Molecular Manufacturing for Clean, Low Cost Textile Production,” in: Proceedings of Ecotextile 04, held in Manchester, UK, 7-8 July 2004, Bolton Institute, Deane Road, UK.

David Forrest participated in a workshop on “Analysis of a Series of Emerging and Potentially Disruptive Advanced Manufacturing Technologies,” at the National Council for Advanced Manufacturing in Washington DC, July 22, 2004.

2003

Neil Jacobstein gave a presentation on “Prospects for Molecular Manufacturing” to an invitation only International Fondazione EL.B.A.NanoForum on Nanoscale Science and Technology co-sponsored by the Max Planck Society: August 28-31, 2003.

Neil Jacobstein spoke at a Cato Institute Panel Discussion Co-sponsored
with The Economist on “Nanotechnology: The Money, Science and Politics of the “Next Big Thing”“, December 11, 2003:

Dr. Forrest served as a reviewer for the report “Nanotechnology for the Intelligence Community,” Committee on Nanotechnology for the Intelligence Community, National Research Council, ISBN: 0-309-55081-5, 19 pages, 8 1/2 x 11, (2005).

2002

A white paper, “Balancing the National Nanotechnology Initiative’s R&D Portfolio,” was presented to the Office of Science and Technology Policy.

Neil Jacobstein gave a presentation on Molecular Nanotechnology as part of a panel on “Nanotech: The Next 10¹⁷ Nanoseconds” moderated by Steve Jurvetson at the Churchill Club, April 17, 2002.

David Forrest was an invited speaker at the Nanoscale Interdisciplinary Research Team’s Reading Nanoscience Workshop, University of South Carolina Philosophy Department, August 2002.

David Forrest, “Perspectives on Nano2002: the Sixth International Conference on Nanostructured Materials,” held at the Rosen Center, Orlando, Florida, 16-21 June 2002. http://www.nanoindustries.com/feature/Nano2002.html.

IMM awarded three IMM Prizes in Computational Nanotechnology at the 10th Foresight Conference on Molecular Nanotechnology.

2001 and before

Neil Jacobstein presented an Aspen Institute Socrates Seminar entitled “Genes, Nanobots, and Megawatts” July 5-8 2001.

David Forrest presented an invited talk entitled, “Molecular Manufacturing: Implications for Polymers,” to the ASTM D-20 Committee on Polymers, Montreal, Canada, 23 July 2001.

David Forrest Presented a seminar on “Molecular Manufacturing and the National Defense” at the Naval Surface Warfare Center, West Bethesda, MD, 24 September 2001.

Dr. Forrest co-organized a session on Nanotechnology at ASM Solutions 2001, November 2001.

David Forrest presented an invited talk entitled, “Molecular Manufacturing Development and Technology Planning,” at the 32nd International SAMPE Technical Conference, Boston, MA, November 2000.

David Forrest organized a session on Molecular Manufacturing at ASM Solutions 2000, October 2000.

IMM Research fellow Dr. John Storrs Hall spoke on “Towards a Hardware Description Language for Molecular Machinery”at the Seventh Foresight Conference on Molecular Nanotechnology (October 15 -17, 1999)

On 26 June 1992 Eric Drexler provided testimony at a Senate hearing. The submitted written testimony and the oral testimony include discussion of environmental applications.

Working Group Proceedings for the International Technology Roadmap for Productive Nanosystems:

Molecular Machine Pathways
Diamondoid Mechanosynthesis
Near-Term Applications

Scientific American debate #2. IMM responds to attacks on the feasibility of molecular assemblers.

Neil Jacobstein, Ralph Merkle, and Robert Freitas, “Balancing the National Nanotechnology Initiative’s R&D Portfolio,” 29 May 2002. A Foresight/IMM White Paper submitted to the White House Office of Science and Technology Policy.

David Forrest, “Molecular Manufacturing Development and Technology Planning,” published in: Proceedings of the 32nd International SAMPE Technical Conference, Society for the Advancement of Material and Process Engineering, held 5-9 Nov. 2000, Boston, MA.

Drexler, K.E., “Building Molecular Machine Systems,” Trends in Biotechnology, Jan. 1999.

Jacobstein, Neil, “Molecular Nanotechnology: Security and Environmental Risk Management,” IMM Report NJ9902, February 1999.

David Forrest, “The Future Impact of Molecular Nanotechnology on Textile Technology and on the Textile Industry,” Proceedings of Discover Expo ’95: Industrial Fabric & Equipment Exposition, held 12 October 1995, Charlotte, North Carolina; pub. Industrial Fabric Association International, 1995.

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In addition, with the author’s permission we have converted the original article on molecular nanotechnology into hypertext format and made it available here:Drexler, K. Eric, “Molecular engineering: An approach to the development of general capabilities for molecular manipulation,” Proceedings of the National Academy of Sciences, September 1, 1981, vol. 78, no. 9, p. 5275-5278.

IMM Reports (#1-50). Topics in Molecular Manufacturing

Working Group Proceedings for the International Technology Roadmap for Productive Nanosystems:

Molecular Machine Pathways
Diamondoid Mechanosynthesis
Near-Term Applications

Scientific American debate #2. IMM responds to attacks on the feasibility of molecular assemblers.

Neil Jacobstein, “Foresight Guidelines,” April 2006.

Neil Jacobstein, Ralph Merkle, and Robert Freitas, “Balancing the National Nanotechnology Initiative’s R&D Portfolio,” 29 May 2002. A Foresight/IMM White Paper submitted to the White House Office of Science and Technology Policy.

Robert A. Freitas Jr., “Diamond Trees (Tropostats): A Molecular Manufacturing Based System for Compositional Atmospheric Homeostasis,” IMM Report 43, 10 February 2010; http://www.imm.org/Reports/rep043.pdf

Drexler, K. Eric, “Building Molecular Machine Systems,” Trends in Biotechnology, Jan. 1999.

Neil Jacobstein “Molecular Nanotechnology: Security and Environmental Risk Management,” IMM Report NJ9902, February 1999.

In 2005 Dr. Forrest prepared a white paper entitled “Molecular Manufacturing Will Change Materials Technology” for the Advisory Technical Awareness Council, the technology “look-ahead” arm of ASM International. The paper assesses the state of the art in progress on molecular manufacturing and provides recommendations to the society.

David Forrest, “Molecular Manufacturing for Clean, Low Cost Textile Production,” in: Proceedings of Ecotextile 04, held in Manchester, UK, 7-8 July 2004, Bolton Institute, Deane Road, UK.

David Forrest, “Perspectives on Nano2002: the Sixth International Conference on Nanostructured Materials,” held at the Rosen Center, Orlando, Florida, 16-21 June 2002. http://www.nanoindustries.com/feature/Nano2002.html.

David Forrest, “Molecular Manufacturing Development and Technology Planning,” published in: Proceedings of the 32nd International SAMPE Technical Conference, Society for the Advancement of Material and Process Engineering, held 5-9 Nov. 2000, Boston, MA.

David Forrest, “The Future Impact of Molecular Nanotechnology on Textile Technology and on the Textile Industry,” Proceedings of Discover Expo ’95: Industrial Fabric & Equipment Exposition, held 12 October 1995, Charlotte, North Carolina; pub. Industrial Fabric Association International, 1995.

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In addition, with the author’s permission we have converted the original article on molecular nanotechnology into hypertext format and made it available here: Drexler, K. Eric, “Molecular engineering: An approach to the development of general capabilities for molecular manipulation,” Proceedings of the National Academy of Sciences, September 1, 1981, vol. 78, no. 9, p. 5275-5278.

IMM promotes the advancement of molecular manufacturing by funding direct research, and by presenting at meetings, seminars, and conferences.

2020

Ted Kaehler, “A Three-Axis Jig for Assembling Molecular Blocks,” 20 October 2020.  A Jig for Molecular Assembly

2019

Nuno R. B. Martins, Amara Angelica, Krishnan Chakravarthy, Yuriy Svidinenko, Frank J. Boehm, Ioan Opris, Mikhail A. Lebedev, Melanie Swan, Steven A. Garan, Jeffrey V. Rosenfeld, Tad Hogg, Robert A. Freitas Jr., “Human Brain/Cloud Interface,” Front. Neurosci., 29 March 2019.  https://www.frontiersin.org/articles/10.3389/fnins.2019.00112/full.

Robert A. Freitas Jr., “Energy Density,” IMM Report 50, June 2019; http://www.imm.org/Reports/rep050.pdf

2018

Guang-Zhong Yang, James Bellingham, Pierre Dupont, Paolo Dario, Peer Fischer, Lucianno Floridi, Robert Full, Neil Jacobstein, Vijay Kumar, Marcia McNutt, Robert Merrifield, Bradley Nelson, Brian Scassellati, Mariarosaria Taddeo, Russell Taylor, Manuela Veloso, Zhong  Lin Wang, Robert Wood. “The Grand Challenges of Science Robotics.” Science Robotics.  31 Jan 2018: Vol. 3, Issue 14, aar7650.”

Tad Hogg, Stress-Based Navigation for Microscopic Robots in Viscous Fluids, J. of Micro-Bio Robots 14:59-67 (2018).  https://arxiv.org/abs/1804.00762

Ralph C. Merkle, Robert A. Freitas Jr., Tad Hogg, Thomas E. Moore, Matthew S. Moses, James Ryley, “Mechanical Computing Systems Using Only Links and Rotary Joints,” Journal of Mechanisms and Robotics, 2018;10(6):061006.  https://arxiv.org/pdf/1801.03534

J. Storrs Hall, Where is My Flying Car?

Kindle books 2018

https://www.amazon.com/dp/B07F6SD34R
http://wimflyc.blogspot.com/p/where-is-my-fly8ing.html

This is a fairly major work of technological history and futurism, covering private aviation, nanotechnology, fusion and other energy sources, regulation, innovation, and technological backlash, and related subjects.

Rob Freitas described it as “awesome.”

2017

Ralph C. Merkle, “New Technologies and Climate Change,” IMM Report 49, June 2017;  http://www.imm.org/Reports/rep049.pdf

Tad Hogg, Matthew S. Moses and Damian G. Allis, “Evaluating the Friction of Rotary Joints in Molecular Machines,” Molecular Systems Design & Engineering, 2:235-252 (2017), DOI: 10.1039/C7ME00021A

2016

Nuno R. B. Martins, Wolfram Erlhagen, Robert A. Freitas Jr., “Human Connectome Mapping and Monitoring Using Neuronanorobots,” J. Evol. Technol. 26(January 2016):1-25. http://jetpress.org/v26.1/martins.htm

Robert A. Freitas Jr., “The Alzheimer Protocols: A Nanorobotic Cure for Alzheimer’s Disease and Related Neurodegenerative Conditions,” IMM Report 48, June 2016; http://www.imm.org/Reports/rep048.pdf

Robert A. Freitas Jr., “The Whiskey Machine: Nanofactory-Based Replication of Fine Spirits and Other Alcohol-Based Beverages,” IMM Report 47, May 2016; http://www.imm.org/Reports/rep047.pdf

Ralph C. Merkle, Robert A. Freitas Jr., Tad Hogg, Thomas E. Moore, Matthew S. Moses, James Ryley, “Molecular Mechanical Computing Systems,” IMM Report 46, March 2016; http://www.imm.org/Reports/rep046.pdf

2015

Robert A. Freitas Jr., “The Nanofactory Solution to Global Climate Change: Atmospheric Carbon Capture,” IMM Report 45, December 2015; http://www.imm.org/wp-content/uploads/2007/07/rep045.pdf

Nuno R.B. Martins, Wolfram Erlhagen, Robert A. Freitas Jr., “Action Potential Monitoring Using Neuronanorobots: Neuroelectric Nanosensors,” Intl. J. Nanomaterials and Nanostructures 1(June 2015):20-41; http://materials.journalspub.info/index.php/IJNN/article/view/107

2014

Robert A. Freitas Jr., “Chapter 3. Temperature Effects On Medical Nanorobots,” in Charles Tandy, ed., The Prospect of Immortality — Fifty Years Later, RIA University Press, Ann Arbor MI, 2014; http://www.amazon.com/The-Prospect-Immortality-Fifty-Years/dp/1934297224

Robert A. Freitas Jr., “The life-saving future of medicine,” The Guardian (U.K.), 29 March 2014 Supplement, back page; http://www.theguardian.com/what-is-nano/nano-and-the-life-saving-future-of-medicine

Tad Hogg, “Using Surface-Motions for Locomotion of Microscopic Robots in Viscous Fluids”, J. of Micro-Bio Robotics 9(3) 61-77 (2014), DOI: 10.1007/s12213-014-0074-z

2013

Tad Hogg, “Distributed Control of Microscopic Robots in Biomedical Applications” in 2nd edition of Advances in Applied Self-Organizing Systems, chapter 8, Mikhail Prokopenko editor, pages 179-208, Springer, 2013.

Denis Tarasov, Ekaterina Izotova, Diana Alisheva, Natalia Akberova, Robert A. Freitas Jr., “Optimal Approach Trajectories for a Hydrogen Donation Tool in Positionally Controlled Diamond Mechanosynthesis,” J. Comput. Theor. Nanosci. 10(September 2013):1899-1907. http://www.molecularassembler.com/Papers/TarasovSep2013.pdf

Robert A. Freitas Jr., “Chapter 6. Diamondoid Nanorobotics,” in Constantinos Mavroidis, Antoine Ferreira, eds., NanoRobotics: Current Approaches and Techniques, Springer, New York, 2013. http://www.amazon.com/Nanorobotics-Approaches-Techniques-Constantinos-Mavroidis/dp/1461421187

Robert A. Freitas Jr., “Chapter 6. Welcome to the Future of Medicine,” in Max More, Natasha Vita-More, eds., The Transhumanist Reader: Classical and Contemporary Essays on the Science, Technology, and Philosophy of the Human Future, Wiley-Blackwell, 2013, pp. 67-72. http://www.amazon.com/The-Transhumanist-Reader-Contemporary-Technology/dp/1118334299

2012

Nuno R.B. Martins, Wolfram Erlhagen, Robert A. Freitas Jr., “Non-destructive whole-brain monitoring using nanorobots: Neural electrical data rate requirements,” Intl. J. Machine Consciousness 4(June 2012):109-140. http://www.nanomedicine.com/Papers/NanoroboticBrainMonitoring2012.pdf

Tad Hogg, Robert A. Freitas Jr., “Acoustic Communication for Medical Nanorobots,” Nano Communication Networks 3(June 2012):83-102. http://arxiv.org/abs/1202.0568

Denis Tarasov, Ekaterina Izotova, Diana Alisheva, Natalia Akberova, Robert A. Freitas Jr., “Structural Stability of Clean and Passivated Nanodiamonds having Ledge, Step, or Corner Features,” J. Comput. Theor. Nanosci. 9(January 2012):144-158. http://www.molecularassembler.com/Papers/TarasovFeb2012.pdf

Robert A. Freitas Jr., “Foreword,” in: Wim Helwegen, Luca Escoffier, eds., Nanotechnology Commercialization for Managers and Scientists, Pan Stanford Publishing Pte. Ltd., Singapore, 2012, pp. xxv-xxvi. http://www.panstanford.com/pdf/9789814364386fm.pdf

Josh Schonwald, “Chapter 19. The Nano Panacea,” in Josh Schonwald, The Taste of Tomorrow: Dispatches from the Future of Food, HarperCollins Publishers, 2012, pp. 262-274. http://www.amazon.com/The-Taste-Tomorrow-Dispatches-Future/dp/0061804215/

Ralph Merkle, “State of Molecular Technology.” Atlantic Council’s Strategic Foresight Initiative (SFI); Stanford University’s Technology Futures and Global Trends. February 27, 2012.

2011

Robert A. Freitas Jr., “Chapter 11. Diamondoid Mechanosynthesis for Tip-Based Nanofabrication,” in Ampere Tseng, ed., Tip-Based Nanofabrication: Fundamentals and Applications, Springer, New York, 2011, pp. 387-400.

Damian G. Allis, Brian Helfrich, Robert A. Freitas Jr., Ralph C. Merkle, “Analysis of Diamondoid Mechanosynthesis Tooltip Pathologies Generated via a Distributed Computing Approach,” J. Comput. Theor. Nanosci. 8(July 2011):1139-1161.

Denis Tarasov, Ekaterina Izotova, Diana Alisheva, Natalia Akberova, Robert A. Freitas Jr., “Structural Stability of Clean, Passivated, and Partially Dehydrogenated Cuboid and Octahedral Nanodiamonds up to 2 Nanometers in Size,” J. Comput. Theor. Nanosci. 8(February 2011):147-167.

Robert A. Freitas Jr., “Nanorobots in Your Future,” What’s Happening Magazine, 15 April 2011.

Robert A. Freitas Jr., Penny Sarchet, “Nanofactories — a future vision,” The Guardian (U.K.), 25 November 2011.

Robert A. Freitas Jr., Stephen Laifer, “Book Review: The Future of Aging,” Life Extension Magazine, September 2011, pp. 81-84.

Tad Hogg, “Robust Self-Assembly Using Highly Designable Structures” at the Black Forest Focus on Soft Matter, Saig, Germany, 25-27 May 2011

Josh Hall, “Further Reflections on the Timescale of AI”, Solomonoff 85th Memorial Conference, Monash Univ, Melbourne, Australia, 30 Nov–2 Dec 2011

Josh Hall, “Ethics for Machines” in Machine Ethics, Michael Anderson & Susan Leigh Anderson (Eds), Cambridge University Press (May 9, 2011) ISBN 0521112354, pp28-46

Josh Hall, (2011) “Ethics for Self-Improving Machines” in Machine Ethics, Michael Anderson & Susan Leigh Anderson (Eds), Cambridge University Press (May 9, 2011) ISBN 0521112354, pp512-523

2010

Robert A. Freitas Jr., Chapter 23. Comprehensive Nanorobotic Control of Human Morbidity and Aging, in Gregory M. Fahy, Michael D. West, L. Stephen Coles, and Steven B. Harris, eds, The Future of Aging: Pathways to Human Life Extension, Springer, New York, 2010, pp. 685-805. http://www.nanomedicine.com/Papers/Aging.pdf

Tad Hogg, Robert A. Freitas Jr., Chemical Power for Microscopic Robots in Capillaries, Nanomedicine: Nanotechnology, Biology, and Medicine 6:298-317 (2010). Full text at arxiv.org

Denis Tarasov, Natalia Akberova, Ekaterina Izotova, Diana Alisheva, Maksim Astafiev, Robert A. Freitas Jr., Optimal Tooltip Trajectories in a Hydrogen Abstraction Tool Recharge Reaction Sequence for Positionally Controlled Diamond Mechanosynthesis, J. Comput. Theor. Nanosci. 7(February 2010):325-353.

Robert A. Freitas Jr., Diamond Trees (Tropostats): A Molecular Manufacturing Based System for Compositional Atmospheric Homeostasis, IMM Report 43, 10 February 2010.

Robert A. Freitas Jr., Long-Term Financial Stability in Cryonics, Cryonics 31(Third Quarter, 2010):4. http://www.alcor.org/cryonics/Cryonics2010-3.pdf

Robert A. Freitas Jr. The Future of Nanomedicine, The Futurist (January-February 2010):21-22

Tad Hogg and Robert A. Freitas Jr., Chemical Power for Microscopic Robots in Capillaries. The work was mostly done during 2009, with minor improvements in early 2010 and the published article appeared in 2010, in the journal Nanomedicine: Nanotechnology, Biology, and Medicine 6:298-317 (2010)

2009

Robert A. Freitas Jr., Meeting the Challenge of Building Diamondoid Medical Nanorobots, Intl. J. Robotics Res. 28(April 2009):548-557. (DOI: 10.1177/0278364908100501) http://www.nanomedicine.com/Papers/MeetChallengeIJRR2009.doc

Robert A. Freitas Jr., Chapter 15. Computational Tasks in Medical Nanorobotics, in M.M. Eshaghian-Wilner, ed., Bio-inspired and Nano-scale Integrated Computing, John Wiley & Sons, New York, 2009, pp. 391-428. http://www.nanomedicine.com/Papers/NanorobotControl2009.pdf

Robert A. Freitas Jr., Medical Nanorobotics: The Long-Term Goal for Nanomedicine, in Mark J. Schulz, Vesselin N. Shanov, eds., Nanomedicine Design of Particles, Sensors, Motors, Implants, Robots, and Devices, Artech House, Norwood MA, 2009, Chapter 14, pp. 367-392.

Robert A. Freitas Jr., Welcome to the Future of Medicine, Studies in Health Technol. Inform. 149(2009):251-256.

Robert A. Freitas Jr., Nanotechnology and Radically Extended Life Span, Life Extension Magazine 15(January 2009):80-85. http://www.lef.org/magazine/mag2009/jan2009_Nanotechnology-Radically-Extended-Life-Span_01.htm

Robert A. Freitas Jr., Nanomedicine, in Stephen Valentine, Timeship, Images Publications, Mulgrave, VIC, Australia, 2009, pp. 10-11.

Ralph C. Merkle, Robert A. Freitas Jr., The Importance of MNT to the Cryonics Community, Cryonics 29(Fourth Quarter, 2008):4-5. (published August 2009) http://www.alcor.org/cryonics/cryonics0804.pdf
http://www.alcor.org/cryonics/cryonics0804.pdf

Ralph C. Merkle, Robert A. Freitas Jr., A Cryopreservation Revival Scenario using MNT, Cryonics 29(Fourth Quarter, 2008):6-8. (published August 2009) http://www.alcor.org/Library/html/MNTscenario.html

Interview with Robert Freitas and Ralph Merkle, Cryonics 29(Fourth Quarter, 2008):9-11. (published August 2009) http://www.alcor.org/cryonics/cryonics0804.pdf

Tad Hogg and Robert A. Freitas Jr., Chemical Power for Microscopic Robots in Capillaries. The work was mostly done during 2009, with minor improvements in early 2010 and the published article appeared in 2010, in the journal Nanomedicine: Nanotechnology, Biology, and Medicine 6:298-317 (2010). Full text at arxiv.org

2008

David Forrest, “Technology Roadmap for Productive Nanosystems,” Nanomanufacturing Conference and Exhibits, Society for Manufacturing Engineers, Framingham, MA, 22-23 April 2008.

2007

David Forrest, Robert Freitas, and Neil Jacobstein provided substantial contributions to the International Technology Roadmap for Productive Nanosystems with three Working Group Proceedings: Molecular Machine Pathways, Diamondoid Mechanosynthesis, and Near-Term Applications. In addition, they provided editing assistance on the Fabrication section.

2004

Robert Freitas and Ralph Merkle co-authored the technical book Kinematic Self-Replicating Machines (Landes
Bioscience, 2004), a landmark survey of the theoretical and experimental literature pertaining to physical self-replicating systems and self-replication.

2002

A white paper, “Balancing the National Nanotechnology Initiative’s R&D Portfolio,” was presented to the Office of Science and Technology Policy.

Tad Hogg is an IMM Research Fellow, and was a Member of the Research Staff at Hewlett-Packard Laboratories and the Xerox Palo Alto Research Center (PARC). Tad holds a PhD from Stanford and BS from Caltech, both in physics.

Tad is an inventor on more than 20 patents, including methods for communicating among microscopic robots and improving the reliability of nano-electronic circuits with defects. He is an author of over 150 peer-reviewed technical publications. These include theoretical studies of medical applications of microscopic robots, which quantify how they could enhance medical technology. Other publications discuss distributed controls for shape-changing robots and defect-tolerant architectures for molecular electronics.

Tad helped organize Foresight Institute workshops on applications of atomically precise manufacturing to medicine, energy and artificial intelligence. He was the industry advisor for a summer research project on microscopic robots at the Institute for Pure and Applied Mathematics (IPAM) at UCLA. He was a visiting faculty member at the multi-agent robotics group of the University of Girona, Spain, and at the Santa Fe Institute summer school on complex systems. Tad presented tutorials on distributed control at an IEEE Swarm Intelligence Symposium, and on combinatorial search and quantum computing at AAAI conferences. He has served on editorial boards of the Journal of Artificial Intelligence Research, the International Journal of Modern Physics, and Autonomous Agents and Multiagent Systems.

The behavior of multi-agent systems, experimental evaluation of economic mechanisms including the use of quantum information processing, heuristic search algorithms for quantum computers, and the effectiveness of peer-production web sites and their social networks are Tad’s other research interests. One example of this work was applying economic principles to distributed computation, in which Tad helped develop and test Spawn, an early market-based distributed resource allocation system for networked computers.

Tad is a Fellow of the American Association for the Advancement of Science (AAAS), a Senior Member of the Association for the Advancement of Artificial Intelligence (AAAI), and a Member of the Tau Beta Pi Engineering Honor Society.

Robert A. Freitas Jr. is Senior Research Fellow at the Institute for Molecular Manufacturing (IMM) in Palo Alto, California, and was a Research Scientist at Zyvex Corp. (Richardson, Texas), the first molecular nanotechnology company, during 2000-2004. He received B.S. degrees in Physics and Psychology from Harvey Mudd College in 1974 and a J.D. from University of Santa Clara in 1979. Freitas co-edited the 1980 NASA feasibility analysis of self-replicating space factories and in 1996 authored the first detailed technical design study of a medical nanorobot ever published in a peer-reviewed mainstream biomedical journal. More recently, Freitas is the author of Nanomedicine, the first book-length technical discussion of the potential medical applications of molecular nanotechnology and medical nanorobotics; the first two volumes of this 4-volume series were published in 1999 and 2003 by Landes Bioscience. His research interests include: nanomedicine, medical nanorobotics design, molecular machine systems, diamond mechanosynthesis or DMS (theory and experimental pathways), molecular assemblers and nanofactories, and self-replication in machine and factory systems. He has published 33 refereed journal publications, 4 books, 61 other publications and several contributed book chapters, filed the first patent on diamond mechanosynthesis, and co-authored Kinematic Self-Replicating Machines (2004), another first-of-its-kind technical treatise.

In conjunction with Foresight Update 39

Nanomedicine: Is Diamond Biocompatible With Living Cells?

By Robert A. Freitas Jr., IMM Research Fellow

In October 1999, IMM Research Fellow Robert A. Freitas Jr. published Volume I of Nanomedicine, his ground-breaking technical work on the medical applications of molecular nanotechnology. Beginning with this issue of the Foresight Update, he will be contributing reports based on his research toward the completion of Volumes II & III of Nanomedicine.

The exteriors of many medical nanorobots [1] and nanorobot aggregates may be made of diamond. That’s why the biocompatibility of diamond surfaces and diamond particles is of considerable interest in nanomedicine [2]. Some nanomedical applications will demand a nonadhesive interface, while other applications may require complete tissue integration with the nanodevice, using biocompatible surfaces of engineered bioactivity, probably including nanostructured materials able to promote and stabilize cell attachment. Atomically-precise diamond surfaces aren’t readily available, so cell responses cannot yet be seriously investigated. However, the biocompatibility of comparatively rough, bulk manufactured diamond surfaces has been addressed experimentally by a handful of researchers — for example, in connection with diamond-coated orthopedic prostheses already proposed, developed, or in clinical use [3]. Here, I focus on one very narrow but important aspect of diamond biocompatibility: the response of living cells to diamond surfaces and particles.

Diamond Surfaces

The first pioneering study of cell response to diamond surfaces was completed by Thomson and colleagues [4] in 1991, using tissue culture plates with diamond-like carbon (DLC) coatings 0.4 microns thick. DLC is an amorphous hydrocarbon polymer with carbon bonding largely of the diamond type instead of the usual graphitic bonding [5], and thus has many of the useful properties of diamond [6]. Mouse fibroblasts grown on the DLC coatings for 7 days showed no significant release of lactate dehydrogenase (an enzyme that catalyzes lactate oxidation, often released into the blood when tissue is damaged) compared to control cells. This demonstrated that there was no loss of cell integrity due to the DLC coatings.

Mouse peritoneal macrophages similarly cultured on DLC also showed no significant excess release of lactate dehydrogenase or of the lysosomal enzyme beta N-acetyl-D-glucosaminidase (an enzyme known to be released from macrophages during inflammation). Morphological examination revealed no physical damage to either fibroblasts or macrophages, confirming the biochemical indication that there was no toxicity and that no inflammatory reaction was elicited in vitro. Follow-up studies [7] in 1994-95 found that mouse macrophages, human fibroblasts, and human osteoblast-like cells grown on DLC coatings on a variety of substrates exhibited normal cellular growth and morphology, with no in vitro cytotoxicity.

Subsequent experiments have largely confirmed these early results. For instance, human hematopoietic myeloblastic ML-1 cells and human embryo kidney cells were observed to proliferate continuously on DLC film with very high viability and no toxicity [8]. Scanning electron microscopy used to investigate the morphological behavior of osteoblasts found that these cells attached, spread and proliferated normally without apparent impairment of cell physiology when placed on DLC or amorphous carbon nitride films, whereas cells placed on silicon were able to attach but not to spread [9]. Human osteogenic sarcoma T385 cells and 1BR3 fibroblasts cultured on DLC-coated wells also showed DLC to be biocompatible [10].

The cytotoxicity study of DLC coatings by Parker and colleagues [11], employing the Kenacid Blue cytotoxicity test in vitro with 3T3-L1 mouse fibroblasts, found normal cell growth on diamond surfaces. Other tests by this team [12] of the biocompatibility of “amorphous carbon hydrogen” using a standard cell line showed that such films are nontoxic to cells, appear to increase cell attachment, and afford normal cell growth rates.

Dion et al. [13] looked at general cytotoxicity and hemocompatibility of DLC surface with 3T3 Balb/c cloned cells, and human endothelial cells isolated from placenta were investigated as a model for differentiating cells. No negative effects due to DLC coatings were observed on the viability of cells, which showed normal metabolic activities.

O’Leary and colleagues [14] evaluated cytotoxicity and cell adhesion of mouse fibroblasts on saddle field source deposited DLC (containing less than 1% hydrogen) coating a titanium alloy surface. They found normal cell adhesion, density, and spreading on DLC.

Jones et al. [15] deposited DLC coatings (by plasma-assisted chemical-vapor deposition (CVD)) and other coatings on titanium substrate and tested their hemocompatibility, thrombogenicity, and interactions with rabbit blood platelets. The DLC coatings produced no hemolytic effect, platelet activation, or tendency towards thrombus formation. Platelet spreading correlated with the surface energy of the coatings.

Finally, an experiment by Tang et al. [16] studied the attachment of neutrophils to plasma-preincubated ~1 cm² 350-micron-thick CVD diamond wafers. Incubation for 1 hour with purified human neutrophils at 2 x 10⁶ cells/cm³ produced an attachment rate of ~400,000 cells/cm² (~0.004 cells/micron²), about the same as for 316 stainless steel and 40% lower than for titanium, two common and well-tolerated implant materials. SEM photographs of CVD diamond wafers implanted intraperitoneally in live mice for 1 week revealed minimal inflammatory response.

Interestingly, on the rougher “polished” surface having ~1 micron features, a small number of spread and fused macrophages 10-13 microns in diameter were present, indicating that some activation had occurred. However, on the smoother “unpolished” surface having <0.25 micron features, samples were partially covered by round, non-spread (non-activated) cells, 4-7 microns in diameter, which had formed no obvious pseudopodia or cell bridges. The authors [16] noted that “the morphology of unpolished surfaces of CVD diamond could be responsible for preventing the activation of surface-adherent cells [but] the mechanism for this differential response of phagocytic cells…is not yet understood.” If surface rugosity [17], topography [18], or crystalline structure [19] can account for the differential response, then it is quite possible that atomically-precise diamondoid surfaces with <1 nm features — constituting much of the external surfaces of medical nanorobots and nano-organs — could be made almost completely macrophage-inactive.

Diamond Particles

In biomaterials research, it has been found [20] that even though a bulk material may be well-tolerated by the body, finely divided particles of the same material can often lead to severe and even carcinogenic complications in test animals. Differences in particle size influence histological reaction [21] and cytokine production [22]. Many nanomedical applications will involve “particle” sized diamondoid objects (e.g., micron-scale individual medical nanorobots), so it is of great interest to review the experimental data relating to the reactions of specific cells to the presence of diamond particles. We already know that finely divided carbon particles are well-tolerated by the body — the passive nature of carbon in tissue has been known since ancient times, and both charcoal and lampblack (roughly spherical 10-20 nm particles) were used for ornamental and official tattoos. Are diamond particles also well-tolerated by cells?

(1) Neutrophils. A 1982 report of possible crystal-induced neutrophil activation by 2-8 micron amorphous diamond crystals [23] has never been confirmed. Indeed, to the contrary, diamond particles are traditionally regarded as biologically inert and noninflammatory [24]. For example, Hedenborg and Klockars [25] used 4-8 micron diamond dust as an inert control in their experimental work, and found that diamond dust did not stimulate the production of reactive oxygen metabolite by polymorphonuclear (PMN) leukocytes — a proposed pathway for chronic inflammation and tissue injury of the lung. Tse and Phelps [24] found that 3-micron diamond dust crystals in a 2 mg/cm³ concentration (~0.06% Nct or “nanocrit” [2]; volume concentration) were phagocytized by 21% of all PMN cells present at a 7250 cell/mm³ concentration after 45 minutes, but no chemotactic activity was generated. Higson and Jones [26] exposed horse and pig neutrophils to urate, hydroxyapatite, pyrophosphate and brushite crystals (all implicated in joint inflammation), which induced superoxide and peroxide generation in a concentration- and temperature dependent fashion. But exposing the neutrophils to diamond crystals at 37 degrees C produced no effect. Yet another experiment [27] tested the ability of various crystals to stimulate phagocytosis, degranulation, and secretion of cell movement (motility) factors (CMFs) from PMN leukocytes and found that hydroxyapatite (HA) crystals stimulated some enzyme release and CMF generation, and monosodium urate monohydrate (MSUM) crystals much more so. But 4-8 micron diamond crystal fragments in suspension up to ~0.2% Nct, while clearly interacting with PMN leukocytes, did not stimulate degranulation, CMF production, or cell death even at high crystal concentrations.

(2) Monocytes and Macrophages. It has long been known that free carbon and diamond particles are ingested by macrophages without harmful effects. For example, cells that have taken up large amounts of 2-4 micron diamond dust remain healthy for at least 30 hours, whereas cells succumb rapidly after ingesting silica [28]. Phosphatase enzyme discharged into diamond-containing phagosomes by adherent lysosomes did not escape into the cytoplasm or nucleus. In a more recent study [29], 2-15 micron particles of diamond, silicon carbide (SiC), hydroxyapatite (HA) and polymethylmethacrylate (PMMA) were suspended in serum-free cultures of human monocytes at a concentration of 0.5 mg/cm³ (~0.01% Nct). All particles were phagocytosed. But while monocyte morphology changed after the ingestion of SiC and HA, there was no change after the ingestion of diamond, indicating no activation of the monocytes by the diamond. Interleukin-1beta production was indistinguishable for control and diamond cultures, but increased 30-fold in the HA cultures, 38-fold in the cultures exposed to SiC, and in a similar range to HA and SiC for the PMMA. The authors [29] concluded that diamond particles in serum-free monocyte culture are inert, despite being phagocytosed, unlike most other particles.

(3) Fibroblasts. Early studies in the 1950s [30] and 1960s [28] found that micron-size diamond dust particles did not induce a fibrogenic reaction. Schmidt et al. [31] note that diamond dust is nonfibrogenic in human monocyte-macrophages found in the lungs; in other words, fibroblasts are not recruited by macrophages in response to the presence of diamond dust. Diamond dust of sizes <0.5 micron and 1-2 microns did not induce the release of thymocyte proliferation factor or fibroblast proliferation factor at diamond particle concentrations up to ~0.1 mg/cm³ (~0.003% Nct) [31]. In another experiment [32], synthetic hydroxyapatite crystals at a concentration of 50 micrograms/cm³ in 1% and 10% serum stimulated ³H thymidine uptake into quiescent canine synovial fibroblasts and human foreskin fibroblast cultures. Calcium pyrophosphate dihydrate crystals also stimulated uptake, as did calcium urate crystals markedly and sodium urate crystals more modestly — but 1-5 micron diamond crystals had no mitogenic effect on the fibroblasts at particle concentrations up to 0.4 mg/cm³ (~0.01% Nct).

(4) Other Cells. The reactions of regenerating rabbit bone tissue to phagocytosable particles were studied [33] by dispersing various particles in hyaluronan and then introducing them into an implant-traversing canal, forming a bone harvest chamber. Tissue that entered the canal during the following 3 weeks was harvested. Particles of high density polyethylene, bone cement and chromium-cobalt injected in this fashion all provoked an inflammatory reaction in tissue entering the canal and caused a marked decrease in the amount of ingrown bone. But the phagocytosable 2-15 micron round-shaped diamond particles — introduced at a number density of ~60 million/cm³ (~0.7% Nct) — produced no decrease in bone formation and appeared “comparatively harmless…there was no obvious cellular reaction to these particles.” Histologically, the diamond particles aggregated into clumps. Occasional macrophages were seen nearby, but phagocytic cells remained few and dispersed, despite containing large amounts of ingested particulate diamond. There was no concentration of macrophages and giant cells such as is usually seen when PMMA or high-density polyethylene particles are implanted. Finally, diamond has never been shown to be neurotoxic [34].

(5) Inflammation and Hemolysis. Tse and Phelps [24] found that 3-micron diamond crystals in a 10 mg/cm3 concentration (~0.3% Nct) injected into canine knee joints produced “little evidence of inflammation” — intra-articular pressure remained low, along with the local cell count. A study by Dion et al. [35] observed no detectable hemolysis in vitro by various ceramic powders tested, including diamond, graphite and alumina, after 60 minutes of exposure to a powder concentration of ~0.5 gm per cm³ of diluted blood (~14% Nct).

Thus it appears that diamond is extremely — indeed outstandingly — biocompatible with living cells.

Acknowledgments

The author thanks Stephen S. Flitman, M.D., and Ronald G. Landes, M.D., for helpful comments on an earlier version of this paper.

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