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.

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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. April 2016
DNA Nanotechnology
Core DNA Nanotechnology Components
13
Holliday Junction Sticky Ends
DNA Lattice
Sources: Shrishaila, DNA Nanotechnology seminar

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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. April 2016
DNA Nanotechnology
Neuroscience Procedures
28
Sources: Menken, The workload of neurosurgeons, 1991.

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. 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. 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. 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. 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. 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