Respirocytes from Patterned Atomic Layer Epitaxy: The Most Conservative Pathway to the Simplest Medical Nanorobot

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Respirocytes from Patterned Atomic Layer Epitaxy:

The Most Conservative Pathway to the

Simplest Medical Nanorobot




Tihamer Toth
-
Fejel

Tihamer.Toth
-
Fejel gd
-
ais.com



2
nd

Unither Nanomedical and Telemedicine Technology Conference

Quebec, Canada

February 24
-
27, 2009

Contents


Technology


Productive Nanosystems


Bio
-
mimetic


Scanning Probes


Tip
-
Based Nanofabrication


Patterned Atomic Layer Epitaxy


Application


Freitas Respirocytes


Requirements


Respirocyte subsystems

Productive Nanosystems

Size matters, atomic precision matters more.

Automated nanoscale tools are most important.

“A closed loop of nanoscale components that make
nanoscale components”


Approaches


Biomimetic methods


Protein engineering


Bis
-
amino acid solid
-
phase self
-
assembly


Structural DNA


Scanning Probe Techniques


Diamond Mechanosynthesis


Patterned Atomic Layer Epitaxy

Protein engineering

Difficult: must solve protein folding problem

Sensitive to small changes in sequence or environment

Low temperature process, but low performance properties

Bis
-
amino acid Solid
-
phase
Self
-
assembly


Protein engineering


Bis
-
amino acid Solid
-
phase Self
-
assembly


Structural DNA

C. Schafmeister, Molecular Lego,

Scientific American
, Feb
2007
, 64
-
71

Structural DNA

50 billion Smiley Faces in two hours

By 1 person with a glorified kitchen oven


Paul W. K. Rothemund, Folding DNA to create nanoscale
shapes and patterns,
Nature

Vol 440,16 March 2006



Courtesy Paul Rothemund

Pixelated DNA and Positioning



courtesy Paul W. K. Rothemund

Ke, et. al., Self
-
Assembled Water
-
Soluble Nucleic Acid Probe Tiles
for Label
-
Free RNA Hybridization Assays,
Science,

Jan 11, 2008

Diamondoid Mechanosynthesis

Adding two carbon atoms at a time

Theory confirmed by 100,000 hours CPU time

2009 experiment funded by UK EPSRC

Tip
-
Based Nanofabrication

DARPA’s Goal:



Automated, parallel nanofabrication


Position, size, shape, and orientation


In
-
situ detection & repair


AFM/STM or similar scanning probes

TBN with Lasers


3

5 ns pulse


NSOM based
ablation


FWHM of 90 nm


Film of unsintered,
1

3 nm gold
nanoparticle
encapsulated by
hexanethiol

300nm

TBN with Dip Pen Nanolithography:
Scanning Probe Epitaxy


Reader tip integrated with
synthesis tip


Dual
-
tip scanning probes
combine contact and non
-
contact modes


Core
-
filled tip with aperture
controls nanostructure
deposition


Control
where, when, and how
a reaction occurs on the
nanometer scale


15 nm limit (so far)

Tip
-
Based Nanofabrication:

Atomically Precise Manufacturing


Produce 3D structures with top
-
down
control and atomic precision.



Inevitable result of continued
improvements in ultra
-
precision
manufacturing



Integration of known techniques



General manufacturing process

Patterned Si ALE

STM tip removes
H atoms from the
Si surface

A precursor gas is
used to dose the
surface. Protected Si
atoms are deposited
only where H has
been removed.

Completed deposition
is verified and then the
deprotection/patterning
is repeated.

Patterned Si ALE

Joe Lyding UIUC

Patterned Si ALE

Joe Lyding UIUC

Room Temperature

10
-
8
Torr disilane

10 minutes/row

5V, 1nA; 7V .1nA; & 6V 1nA

6nm high features

Tip Arrays


MEMS


55,000 tips


15 nm resolution


Fast

Freitas Respirocytes


Atomically Precise Diamondoid


1000 nm (1
μ
m); 1000 atm


Requirements
Analysis:
What & How


Subsystems


Red Blood Cell Function


O
2

not soluble in water


Four hemes; one O
2

each


68,000 daltons


Lasts longer & more
effective inside cells

Hemoglobin

Hemoglobin Saturation


150 quintillion (10
18
) hemoglobin
molecules in 100 ml whole blood


Binding regulated by O2 partial pressure

Hemoglobin % Saturation

partial pressure oxygen (mm Hg
)

Hemoglobin Saturation: Bohr Effect


Lower pH
-
> lower saturation


Higher CO
2

-
> more oxygen delivered


Higher temperature also shifts curve right

Hemoglobin % Saturation

partial pressure oxygen (mm Hg
)

Oligosaccharide and Rhesus
Protein Coating

Perfluorocarbons

PFCs dissolve > 100x O
2

than blood serum

PFCs are hydrophobic & require emulsifiers


Perfluorocarbons surrounded
by a surfactant (lecithin)


Up to twice as efficient as RBC
(at high partial pressure)


No refrigeration required


1/40
th

size of RBC


May increase risk of stroke in
cardiac patients


Short term (hours)

Respirocyte Subsystems


Pressure Vessels


Pumps


Power


Communications


Sensors


Onboard Computation


1000 nm Spherical Pressure Vessels

APM Diamond


1,000,000 MPa

5 nm (~30 carbon atoms) walls

10,000 atm (but diminishing returns after 1000 atm)


Silicon (Crystalline, low defects)

30,000 MPa

10 nm walls

1,400 atm


Blood cells (or serum PFCs)

0.51 atm

0.13 atm deliverable to tissues (less for PFCs)

Location Dependent Pressure

Output O
2

Input CO
2

High
-
Pressure

Low
-
Pressure

Intake O
2

Output CO
2

Body Tissue

Capillaries

Lung

Capillaries

Ratiometric Oxygen Nanosensor

PEBBLE nanosensor


Ruthenium
-
DPP
(Oxygen sensitive dye)


Oregon Green Dye


Nanoscale pH Sensor


Zinc Oxide Nanowires


AlGaN/GaN junctions


Field tested outdoors

Selective Pumps

Water Pump


Neon Pump

Selective Pump:

Combined motor and rotor

Sodium
-
Potassium

Exchange

Pump


Small (12 nm diameter)


17 RMP (no load)


100 picoNewtons


Runs on ATP


Elegant


Difficult to integrate with silicon shell


Selective Oxygen Rotor


Cascaded Selective Rotors

Blood

Plasma

Kinesin

2 ATP/cycle

2 steps/cycle(rotation/slide)

16 nm per cycle

100 steps/second

~5 picoNewtons

40% efficient


Kinesin
-
based

Motors


Glucose


ATP

Three out of 10 enzymes have been attached

PH

40% efficient


Carbon Dioxide Return

Carbonic anhydrase


1 million times faster


30,000 daltons

Issues:

Detecting CO
2

presence

Getting CO
2

out of heme


Bicarbonate Sequestering

CmpA Protein

Highly selective

452 residues


52,000 daltons


Selective Carbon Dioxide Rotor

Non
-
Selective Pumps

3
-
valve peristaltic Micropump

Piezoelectric

100 V (peak
-
to
-
peak)

100 Hz

17.6 microliters/minute

Selective Membranes

Denissov, Molecular Sieves for Gas Separating Membranes

Computation:

Quantum Dot Cellular Automata


Arbitrary Boolean logic


Single electron charge


Very low power consumption

Production Issues


By 2012: Ten million atoms/hour (silicon)


Nanoimprint lithography


Multiple materials


ALE does not work for complex proteins


Bootstrapping


Small STM arrays build larger STM arrays


Build fabrication and assembly lines


Smaller vacuum chambers

Thank you!


Questions?



Tihamer Toth
-
Fejel

Tihamer.Toth
-
Fejel gd
-
ais.com