BCIs and DNA Nanotechnology

April 8, 2016, Miami FLSlides: http://slideshare.net/LaBlogga

DNA Nanotechnology

Applications in Brain-Computer Interfaces (BCIs) and

NanoneurosurgeryImage credit: mashpedia.com

Melanie SwanNew School, New York NY

[email protected]

April 2016DNA 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.

April 2016DNA Nanotechnology

Thesis

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DNA Nanotechnology is uniquely suited to advance the development of Brain-Computer

Interfaces (BCIs) and aid in Nanoneurosurgery


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

4Source: 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


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

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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

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BCIs: Non-Invasive, Semi-Invasive, Invasive

7Source: http://www.slideshare.net/ajaygeorge91/bci-ppt

Signal capture at multiple levels, external and internal


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

8Source: http://www.asha.org/public/hearing/Cochlear-Implant-Frequently-Asked-Questions/


Two-way BCIs: Input/Output

9Source: 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


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

10Source: http://www.wtec.org/bci/


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)

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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


Core DNA Nanotechnology Components

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Holliday Junction Sticky Ends

DNA Lattice

Sources: Shrishaila, DNA Nanotechnology seminar


Core DNA Nanotechnology Components

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DNA WalkerNano-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


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)

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1. Blood clot dissolution2. Microneedle array diagnostics/delivery3. Hydrogel cellular delivery4. Molecular robot for positional

nanoassembly5. Nanotechnology-guided neural

regeneration6. DNA Nanobots in first human trial 7. Graphene electrode-neuron interface8. Nanobots cargo delivery in mouse

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Neocortical Neurogenesis in Mammalslafayette.edu

Top 8 DNA Nanotechnology Advances for BCIs


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)

17Sources: 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


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)

18Sources: 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


DNA Nanotechnology Killer App Microneedle Array Diagnostic/Delivery

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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


Microchanneled hydrogel

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DNA Nanotechnology Killer AppHydrogel 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


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


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

22Sources: Shah et al, Nanotechnology-Based Approaches for Guiding Neural Regeneration, 2016.

Shreyas Shah, Rutgers and Physiological Communications, Bell Labs


DNA Nanotechnology Killer App DNA Nanobots in First Human Trial

23Sources: 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


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


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/nn507097khttp://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


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

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Lumbar Puncture Burr Hole (Craniotomy) Blood clot removal Spinal fluid check Subdural hematoma drain

Available Applications:DNA Nanotechnology

Needed Applications:Nueronanosurgery


Neuroscience Procedures

61% Spinal Surgery23% Cranial12% Peripheral Nerve 4% Miscellaneous

27Sources: http://www.medscape.com/viewarticle/515636_3, Menken, The workload of neurosurgeons, 1991.

66% Lumbosacral32% Cervical12% Thoracic

Procedures 83% minor: spinal puncture, myelography, arteriography17% major: laminectomy, discectomy, craniotomy


Neuroscience Procedures

28Sources: Menken, The workload of neurosurgeons, 1991.


Progression and Phased Transition

29Sources: Swan, M. Cognitive Applications of Blockchain Technology. Cognitive Science 2015.Hildt, DNA Nanotechnology, 2013

Highly Invasive

Lumbar PunctureBurr Hole (Craniotomy)

Somewhat Invasive

Microneedle ArrayMicrofluidics

Minimally Invasive

DNA Nanotechnology Diagnostics

Current Methods Nanotechnology Methods

Cost: $3000/per


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

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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

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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

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Thesis

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DNA Nanotechnology is uniquely suited to advance the development of Brain-Computer

Interfaces (BCIs) and aid in Nanoneurosurgery

April 8, 2016, Miami FLSlides: http://slideshare.net/LaBlogga

Image credit: mashpedia.com

Melanie SwanNew School, New York NY

[email protected]

Thank you!

DNA Nanotechnology

Applications in Brain-Computer Interfaces (BCIs) and

Nanoneurosurgery

BCIs and DNA Nanotechnology

Technology

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