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BCIs and DNA Nanotechnology

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This talk provides a review of the current status of research related to self-assembling DNA nanotechnology (particularly DNA nanostructures, synthetic biology, and DNA origami scaffolding structures) and how the self-assembly of artificial systems might be applied in the context of neuro-nanomedicine. One application of self-assembling DNA nanotechnology might be new forms of brain-computer interfaces (BCIs) that are less invasive than current computer chip-based hardware solutions. Another application of self-assembling DNA nanotechnology might be high-resolution neocortical recording devices where synthetic molecules would assemble a DNA signature every time a neuron was fired.

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BCIs and DNA Nanotechnology

  1. 1. April 8, 2016, Miami FL Slides: http://slideshare.net/LaBlogga DNA Nanotechnology Applications in Brain-Computer Interfaces (BCIs) and Nanoneurosurgery Image credit: mashpedia.com Melanie Swan New School, New York NY m@melanieswan.com
  2. 2. April 2016 DNA Nanotechnology 2 About Melanie Swan  Founder DIYgenomics, Institute for Blockchain Studies, GroupPurchase  New School, Singularity University Instructor, IEET Affiliate Scholar, EDGE Contributor  Education: MBA Finance, Wharton; BA French/Economics, Georgetown Univ  Work experience: Fidelity, JP Morgan, iPass, RHK/Ovum, Arthur Andersen  Sample publications: Source: http://melanieswan.com/publications.htm  Kido T, Kawashima M, Nishino S, Swan M, Kamatani N, Butte AJ. Systematic Evaluation of Personal Genome Services for Japanese Individuals. Nature: Journal of Human Genetics 2013, 58, 734-741.  Swan, M. The Quantified Self: Fundamental Disruption in Big Data Science and Biological Discovery. Big Data June 2013, 1(2): 85-99.  Swan, M. Sensor Mania! The Internet of Things, Wearable Computing, Objective Metrics, and the Quantified Self 2.0. J Sens Actuator Netw 2012, 1(3), 217-253. Swan, M. Health 2050: The Realization of Personalized Medicine through Crowdsourcing, the Quantified Self, and the Participatory Biocitizen. J Pers Med 2012, 2(3), 93-118.  Swan, M. Steady advance of stem cell therapies. Rejuvenation Res 2011, Dec;14(6):699-704.  Swan, M. Multigenic Condition Risk Assessment in Direct-to-Consumer Genomic Services. Genet Med 2010, May;12(5):279-88.
  3. 3. April 2016 DNA Nanotechnology Thesis 3 DNA Nanotechnology is uniquely suited to advance the development of Brain-Computer Interfaces (BCIs) and aid in Nanoneurosurgery
  4. 4. April 2016 DNA Nanotechnology BCI market estimated at $1.7 billion in 2022  Brain-Computer Interface (BCI) market estimated to grow to USD $1.7 billion by 2022 (doubling in 7 years)  Sample Vendors: Emotiv System, Mind Solutions Corp., Puzzlebox, Natus Medical, Interactive Productline, Compumedics Ltd., Neuroelectrics 4 Source: http://www.medgadget.com/2016/03/brain-computer-interface-bci-market-is-expected-to-grow-owing-to-its-increasing- demand-in-healthcare-industry-till-2022-grand-view-research-inc.html, http://www.grandviewresearch.com/industry-analysis/brain- computer-interfaces-market Global brain computer interface market, by application, 2012-2022 (USD Million) – Grand View Research
  5. 5. April 2016 DNA Nanotechnology What is a Brain-computer Interface (BCI)?  A brain-computer interface (BCI), brain- machine interface (BMI), or neural prosthesis is any technology linking the human brain to a computer  A computational system implanted in the brain that allows a person to control a computer using only brainwaves; e.g.; electrical signals from the brain 5
  6. 6. April 2016 DNA Nanotechnology How does a BCI work?  Wearer type characters onto a computer screen as…  …the BCI registers the electrical output of the brain when the eyes are focused on a particular place on the computer screen  On the "q" in a matrix of on- screen letters for example, to produce "q" to appear as output on the monitor 6
  7. 7. April 2016 DNA Nanotechnology BCIs: Non-Invasive, Semi-Invasive, Invasive 7 Source: http://www.slideshare.net/ajaygeorge91/bci-ppt  Signal capture at multiple levels, external and internal
  8. 8. April 2016 DNA Nanotechnology BCIs in Practical Use  Repair human cognitive and sensory- motor function  Cochlear implants: a small computer chip is substituted for damaged inner ear control organs, sound waves transformed into brain-interpretable electrical signals  Over 70,000 US (219,000 global); 50% in children (2010)  Vision restoration: implantable systems transmit visual information to the brain 8 Source: http://www.asha.org/public/hearing/Cochlear-Implant-Frequently-Asked-Questions/
  9. 9. April 2016 DNA Nanotechnology Two-way BCIs: Input/Output 9 Source: R.A. Miranda et al. / Journal of Neuroscience Methods 244 (2015) 52–67  Input channels use electrical brain stimulation to deliver signals to the brain  Output channels collect the action potentials of single neuron spikes or scalp electrical signals into commands that move robot arms, wheelchairs, and cursors
  10. 10. April 2016 DNA Nanotechnology Areas of BCI Advancement needed  DNA Nanotechnology can help …  Improved implantable components  Bioengineered multi-electrode sensing arrays  Biocompatible electrodes and arrays  Miniaturized actuators, components  Improved signal detection  Neural spike train signals (action potentials)  Conductive gels  Novel cortical delivery approaches  Nanodevices 10 Source: http://www.wtec.org/bci/
  11. 11. April 2016 DNA Nanotechnology BCI Applications of DNA Nanotechnology  Pathology Resolution  Improve control of neuro-prosthetics and prosthetic limbs  Smooth the irregular neural electrical activity in epilepsy, Parkinson’s Disease  Amplify neuronal signaling in neurodegenerative disease  Environmental Support  Maintain healthy conductive environment  Neuronal repair  Activate neuronal arrays (optogenetics) 11
  12. 12. April 2016 DNA Nanotechnology 12 DNA Nanotechnology  Using DNA as a construction material; nanoscale building blocks  Specificity of the interactions between complementary base pairs make DNA a useful construction material  DNA ladder framework  Self-assembles, known properties, predictable shapes  Ready availability raw nucleic acids  Dynamically reprogrammable DNA, RNA, peptides  Use DNA as a building block to self- assemble structures in vivo
  13. 13. April 2016 DNA Nanotechnology Core DNA Nanotechnology Components 13 Holliday Junction Sticky Ends DNA Lattice Sources: Shrishaila, DNA Nanotechnology seminar
  14. 14. April 2016 DNA Nanotechnology Core DNA Nanotechnology Components 14 DNA Walker Nano-sized Lock Box (drug delivery) DNA origami is the nanoscale folding of DNA to create non- arbitrary two- and three-dimensional shapes at the nanoscale. DNA Origami
  15. 15. April 2016 DNA Nanotechnology Top 8 DNA Nanotechnology Advances for BCIs  Method: select advances representative of larger field  Sources: FNANO industry conference, PubMed searches, high-profile DNA nanotechnology labs (NYU, Caltech, Harvard, Stanford, Univ of Manchester) 15
  16. 16. April 2016 DNA Nanotechnology 1. Blood clot dissolution 2. Microneedle array diagnostics/delivery 3. Hydrogel cellular delivery 4. Molecular robot for positional nanoassembly 5. Nanotechnology-guided neural regeneration 6. DNA Nanobots in first human trial 7. Graphene electrode-neuron interface 8. Nanobots cargo delivery in mouse 16 Neocortical Neurogenesis in Mammals lafayette.edu Top 8 DNA Nanotechnology Advances for BCIs
  17. 17. April 2016 DNA Nanotechnology DNA Nanotechnology Killer App Blood Clot Dissolution  Problem: dissolve life-threatening blood clots in stroke  Novel nanotherapeutic for clearing obstructed blood vessels: biodegradable nanoparticle aggregate coated with tissue plasminogen activator (tPA) (clot-busting drug) 17 Sources: Marosfoi, et al (2015) Shear-Activated Nanoparticle Aggregates Combined With Temporary Endovascular Bypass to Treat Large Vessel Occlusion Donald Ingber, Wyss Institute and Ajay Wakhloo, U Mass
  18. 18. April 2016 DNA Nanotechnology DNA Nanotechnology Killer App Blood Clot Dissolution  Novel approach for complete vascular blockages where there is no blood flow (the usual case for stroke)  The nanotherapeutic reacts to fluid shear force, releasing tPA-coated nanoparticles in narrowed regions where vessels are occluded, binding to the blood clot and dissolving it  Application: less-invasive alternative to existing method (stent-retriever thrombectomy procedure) 18 Sources: Marosfoi, et al (2015) Shear-Activated Nanoparticle Aggregates Combined With Temporary Endovascular Bypass to Treat Large Vessel Occlusion Donald Ingber, Wyss Institute and Ajay Wakhloo, U Mass
  19. 19. April 2016 DNA Nanotechnology DNA Nanotechnology Killer App Microneedle Array Diagnostic/Delivery 19  Problem: less-invasive diagnostic/delivery  Implantable microneedle array mimics normal arachnoid granulations surrounding the brain and spinal cord  Microfabricated arachnoid granulations punctured through dura mater membrane in the brain to provide a conduit for cerebrospinal fluid flow (porcine tests)  Application: hydrocephalus treatment  Communicating Hydrocephalus caused by deficient arachnoid granulation valves that poorly regulate cerebrospinal fluid flow Sources: Oh et al, A novel microneedle array for the treatment of hydrocephalus, 2015. Jonghyun Oh, Chonbuk National University, Korea and Tim Medina, Drexel University
  20. 20. April 2016 DNA Nanotechnology Microchanneled hydrogel 20 DNA Nanotechnology Killer App Hydrogel Cellular Delivery Sources: Kim et al, Artificially Engineered Protein Hydrogels Adapted from the Nucleoporin Nsp1 for Selective Biomolecular Transport, 2015.; https://www.cce.caltech.edu/content/chemical-engineering-seminar-126, Lee et al, A bio-inspired, microchanneled hydrogel, 2015.  Problem: selective permeability of the hydrogel-coated lipid bilayer  Artificially-engineered protein hydrogels  Nucleosporin-like polypeptide hydrogels mimic nucleosporin to access the nucleus  Tunable mechanical and transport properties  Microchanneled hydrogel scaffolding ability to control spatial organization of biomolecules in a 3D matrix  Application: selective biomolecular transport, transport protein cargo, molecular separation Katharina Ribbeck, Biological Engineering, MIT
  21. 21. April 2016 DNA Nanotechnology 21 DNA Nanotechnology Killer App Molecular Robot for Positional Nanoassembly Sources: Kaszemm et al, Pick-up, transport and release of a molecular cargo using a small-molecule robotic arm, 2016. http://www.nature.com/nchem/journal/v8/n2/pdf/nchem.2410.pdf.  Problem: Small-molecule transport and assembly  Artificial robotic arm transports molecular cargo by inducing conformational and configurational changes  Results: 79–85% of 3- mercaptopropanehydrazide molecules transported between platform sites without cargo dissociation  Application: reposition single molecules; atom-length scale positioning David Leigh, University of Manchester, http://www.catenane.net
  22. 22. April 2016 DNA Nanotechnology DNA Nanotechnology Killer App Nanotechnology-guided Neural Regeneration  Problem: directed neural stem cell differentiation into neurons and oligodendrocytes  Nanoparticle-based system to deliver nanomolecules to the microenvironment to modulate cell surface chemistry  Surface properties influence changes in cell adhesion, shape, and spreading  Nanoscaffolds enhance gene delivery, facilitate axonal alignment  Application: regenerate damaged nerve tissue 22 Sources: Shah et al, Nanotechnology-Based Approaches for Guiding Neural Regeneration, 2016. Shreyas Shah, Rutgers and Physiological Communications, Bell Labs
  23. 23. April 2016 DNA Nanotechnology DNA Nanotechnology Killer App DNA Nanobots in First Human Trial 23 Sources: Amir et al, Folding and Characterization of a Bio-responsive Robot from DNA Origami, 2015. Hachmon et al, A Non- Newtonian Fluid Robot, 2016. http://nextbigfuture.com/2015/05/pfizer-partnering-with-ido-bachelet-on.html  Problem: Targeted cancer treatment less destructive than chemo and radiation  DNA Nanobots: single strand DNA folded into clamshell shaped box  Clamshell contains existing cancer drugs  Protective box has two states  Closed during targeted transport  Open to disgorge cancer drug to expose cancerous cells  Application: targeted drug delivery Ido Bachelet, Bar-Ilan University and Pfizer
  24. 24. April 2016 DNA Nanotechnology 24 DNA Nanotechnology Killer App Graphene Electrode-Neuron Interface Sources: Fabbro et al, Graphene-Based Interfaces Do Not Alter Target Nerve Cells, 2016. http://www.gizmag.com/graphene-electrode- brain-disorders/41591/  Problem: Effective implantable electrode materials to interface with human neurons  Created direct graphene-to-neuron interface where neurons retained signaling properties (rat brain culture)  Improvement over currently implanted electrodes (tungsten and silicon) which have scar tissue and high disconnection rate per stiff materials; pure graphene is flexible, non-toxic  Application: restore lost sensory function Laura Ballerini, University of Trieste; Andrea Ferrari, Cambridge University
  25. 25. April 2016 DNA Nanotechnology 25 DNA Nanotechnology Killer App Nanobots Cargo Delivery in Live Mouse  Problem: Wider range of targeted in vivo delivery methods  Nanobot micromotors delivered first medical payload in living creature (mouse stomach tissue) Sources: Gao, Artificial Micromotors in the Mouse's Stomach, 2015. http://pubs.acs.org/doi/ipdf/10.1021/nn507097k http://www.gizmag.com/nanobot-micromotors-deliver-nanoparticles-living-creature/35700/?li_source=LI&li_medium=default-widget Joseph Wang, Nanoengineering, UCSD  Zinc-coated synthetic micromotors used stomach acid-driven propulsion to install themselves in the stomach wall  Micromotor bodies dissolved in gastric acid, releasing cargo, leaving nothing toxic behind  Application: Autonomous delivery and release of therapeutic payloads in vivo, cell manipulation
  26. 26. April 2016 DNA Nanotechnology Approaching overlap in DNA Nanotechnology and Neuronanosurgery  Imaging (quantum dot)  Drug delivery (nanoparticles)  Treatment and Intervention  Diagnostics  Remediation (clean-up)  Research, simulation, test  Animal models  Prepare the surgical environment 26  Lumbar Puncture  Burr Hole (Craniotomy)  Blood clot removal  Spinal fluid check  Subdural hematoma drain Available Applications: DNA Nanotechnology Needed Applications: Nueronanosurgery
  27. 27. April 2016 DNA Nanotechnology Neuroscience Procedures 61% Spinal Surgery 23% Cranial 12% Peripheral Nerve 4% Miscellaneous 27 Sources: http://www.medscape.com/viewarticle/515636_3, Menken, The workload of neurosurgeons, 1991. 66% Lumbosacral 32% Cervical 12% Thoracic Procedures 83% minor: spinal puncture, myelography, arteriography 17% major: laminectomy, discectomy, craniotomy
  28. 28. April 2016 DNA Nanotechnology Neuroscience Procedures 28 Sources: Menken, The workload of neurosurgeons, 1991.
  29. 29. April 2016 DNA Nanotechnology Progression and Phased Transition 29 Sources: Swan, M. Cognitive Applications of Blockchain Technology. Cognitive Science 2015. Hildt, DNA Nanotechnology, 2013 Highly Invasive Lumbar Puncture Burr Hole (Craniotomy) Somewhat Invasive Microneedle Array Microfluidics Minimally Invasive DNA Nanotechnology Diagnostics Current Methods Nanotechnology Methods Cost: $3000/per
  30. 30. April 2016 DNA Nanotechnology Conclusions  DNA nanotechnology: specifiable building block for building in-vivo structures  Pathology resolution: blood clot dissolution  Diagnostics and drug delivery: microneedle array, hydrogel, nanorobot drug delivery  In situ molecular construction: positional nanoassembly, nano- guided neural regeneration, electrode component construction and repair 30
  31. 31. April 2016 DNA Nanotechnology Future Applications  DNA nanotechnology might provide requisite functionality in the design of next-generation BCIs  Using self-assembling DNA nanotechnology to create new forms of BCIs that are less invasive than current computer chip-based hardware solutions  Deploying DNA nanotechnology in high-resolution neocortical recording devices where synthetic molecules would assemble a DNA signature every time a neuron was fired 31
  32. 32. April 2016 DNA Nanotechnology Philosophy of BCIs and DNA Nanotechnology  BCIs: external aid or human and machine in integrated synthesis and collaboration?  What do BCIs mean for what it is to be human?  Fundamentally not just human + tech tool  24-7 connectivity means human cognitive processing continuously linked to the Internet and other minds  What is it if the human cannot not be online?  Unavoidable bifurcation into different gradations of improved and unimproved humans? (those not augmenting with BCIs)  BCI aesthetics inhibit adoption; need ‘Apple design’ uplift to make BCIs beautiful 32
  33. 33. April 2016 DNA Nanotechnology Thesis 33 DNA Nanotechnology is uniquely suited to advance the development of Brain-Computer Interfaces (BCIs) and aid in Nanoneurosurgery
  34. 34. April 8, 2016, Miami FL Slides: http://slideshare.net/LaBlogga Image credit: mashpedia.com Melanie Swan New School, New York NY m@melanieswan.com Thank you! DNA Nanotechnology Applications in Brain-Computer Interfaces (BCIs) and Nanoneurosurgery

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