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10 December 2010
ICOD: 10 December 2010
DIA-08-1102-005
Defense 
Intelligence 
Reference 
Document
D efense Fu tu res
Quantum Computing and 
Utilizing Organic Molecules in 
Automation Technology
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Quantum Computing and Utilizing Organic Molecules in 
Automation Technology
The Defense Intelligence Reference Document provides non-substantive but 
authoritative reference information related to intelliqence topics or methodoloqies.
Prepared by:
Technology Warning Division (DWO-4)
Defense Warning Office 
Directorate for Analysis 
Defense Intelligence Agency
Author:
AAP Person 73
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This product is one in a series of advanced technology reports produced in FY 2010 under the 
Defense Intelligence Agency, Defense Warning Office's Advanced Aerospace Weapon System 
Applications fAAWSA) Program. Comments or questions pertaining to this document should be 
addressed to|AAP Person 1 | AAWSA Program Manager, Defense Intelligence Agency,
ATTN: JU1AF - DI/DWO-3, Bldg 6000, Washington, DC 20340-5100.
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Contents
Summary.............................................................................................................................5
Introduction.......................................................................................................................7
Ultrafast Computing Power in Aerospace Applications.....................................................7
Making Digital Circuits Faster..................................................................................  8
Applications of Quantum Computers............................................................................10
The Closed Box and Fault Tolerance.........................................................  11
Scalability...........................................................................    12
Universal Logic......................    12
Initialization and Measurement....................................................................................13
The Quantum Dot Approach................................................  13
Electrostatic Quantum Dots in Graphene.................................................................14
Quantum Dots in Graphene Nanoribbons....................................    15
Graphene Disc in Single-Layer Graphene................................................................16
Graphene Disc in Bilayer Graphene.................................................    17
Manipulation of Spin Qubits in Graphene Quantum Dots Relative to GaAs...........18
Spin Relaxation and De-phasing in Graphene Quantum Dots................................19
Spin Relaxation Due to Spin-orbit Interaction..........................  20
Research with Graphene Quantum Dots...............................................................  21
Summary of Additional Inorganic Technologies..........................................................21
Photon Technologies..................................................................      21
Ion and Atomic Trap Technologies...........................................................................22
Nuclear Magnetic Resonance (NMR) Technologies.....................  22
Superconducting Technologies.................................................................................22
DNA-based Designs for Molecular Computers..............................................................23
DNA Background...................................................................................  23
Error Suppression Mechanisms in DNA Self-Assembly............................................28
Self-assembly with DNA-based Microfluidic Devices..............................................31
DNA Origami...................................................................................................  32
Engineering DNA-Based Logic Gates...........................................  35
Logic Operation by Deoxyribozymes.......................................................................35
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Deoxyribozyme-based Boolean Automata.................................  39
Robotic Bases (The DNA Robot) ...............................................................................40
DNA Nanomotors........................................................................  41
The Nano Walker; a Spider-like Approach..............    43
Discussion.....................................................................................................................45
Conclusion..........................................................................  46
References....................................................................................................................48
Figures
Figure 1. Hexagonal structure of graphene...................................................................  14
Figure 2. Quantum dot in graphene nanoribbon..............................................................15
Figure 3. Left; Energy diagram for quantum dot in single-layer graphene. Right; Bound 
state levels as function of dot radius.........................................  16
Figure 4. (a) Color scale plot of the transconductance, (b) One of the vertices of the 
honeycomb structure at Vsd = 800 pV: Charge stability diagrams for series- 
coupled quantum dots.............      16
Figure 5. Quantum dot in bilayer graphene...............................................  17
Figure 6. Bilayer graphene tunneling device structure....................................................18
Figure 7. Qubit piano.........................................................................................................19
Figure 8. Long distance coupling of three graphene qubits..............................  19
Figure 9. A DNA nanomachine driven by repeated sequential addition of DNA control 
strands.          23
Figure 10. Recombinant DNA molecule with restriction enzyme cleavage and sticky end 
ligation...............................................................  25
Figure 11. Two symmetric DNA nanomotifs and the crystals grown using them.. .........26
Figure 12. (top a-e) The XOR Cellular Automaton and Its Implementation by Tile-Based
Self-Assembly............................................................................    27
Figure 12 (continued), (bottom a-e) AFM Images of Algorithmic Self-assembly of 
Sierpinski Triangle Crystals.................    28
Figure 13. Error Suppression with the PTM Method..........................................    30
Figure 14. Simulation results of growth in (A) the OTM, (B) the PTM, and (C) the LTM.30
Figure 15. Three Types of Error in DNA Tile Self-assembly (a) Growth error (b) Facet 
error (c) Nucleation error. Red lines indicate the mismatched sides............31
Figure 16. Micro-fluidic device for DNA tile self-assembly..............................................32
Figure 17. (A) Schematic diagram of a 16-column microfluidic DNA synthesizer 
(B) Close up schematic of the column array................................33
Figure 18. Design of DNA origami.....................................................................................34
Figure 19. Several DNA origami folding paths..................................................................34
Figure 20. Functional design of a DNA based logic gate...........................................  37
Figure 21. Simplistic rendering of a DNA logic gate.................................  38
Figure 22. Basic gate structures, derived from allosterically regulated deoxyribozyme 
E6, for playing tic-tac-toe against a human opponent.................39
Figure 23. First Generation (MAYA I) DNA-based Logic Circuit that plays tic-tac-toe... 40
Figure 24. A single molecule DNA-based nanomotor driven by photons.........................42
Figure 25. AFM Scan of walkers as they follow a track pattern places on the surface. . 43
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Figure 26. The Nano walker made at Columbia University is a protein molecule 
decorated with three legs—single-stranded DNAzymes, synthetic DNA  
molecules that act as enzymes and catalyze a reaction........  44
Figure 27. Deoxyribozyme-based molecular walker and origami prescriptive landscape. 
...............................................................        45
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Quantum Computing and Utilizing Organic Molecules in 
Automation Technology
Summary
Powerful onboard com puting hardware is a desired option for future space travel. W ithout 
large data processing capability, the copious am ounts of data acquired during flight from  
astronom ical sensors as well as crew and vehicle sensors will need to be sent back to 
earthbound m achines for processing, introducing delays m easured in hours for routine 
calculations. C urrent com m ercial com puter hardware trajectories in silicon substrate 
sem iconductors are not likely to produce a radiation-hard or sm all and portable 
supercom puter without significant m ission-specific alteration. Alternatives to traditional 
com puting technology include com puters based on entangled quantum  states and m olecular 
com puting hardware based on D NA m olecules.
Included in this review is significant introduction to the necessary elem ents of quantum  
com puting and a sum m ary of the state-of-the-art technologies. Following is background on 
D NA and production of engineered D NA chains. Finally, D NA logic gates are presented along 
with a treatm ent of nanom achines that will repair D NA circuitry. Forecasts of technology 
developm ent in the 1 0-20 and 4 0-year horizons are included along the way, as well as 
sum m ary discussion and a conclusion.
T he first operating quantum  com puters capable of solving real-world problem s will 
com m ence within 1 0 years and be based on ion trap technology. T his is entirely based on the 
am ount of research resources dedicated to the problem  and the fact that there appear to 
only be engineering challenges rem aining. Atom ic and ion traps require very substantial 
cryogenic and EM shielding system s and are not practical for space travel.
Pure photonic technologies available today have difficulty with both m iniaturization and 
scalability. However, the am ount of active work in the field m akes a disruptive advance likely 
in the 1 0-year tim efram e. O ptical com puters will likely be realized in the 20-year horizon; 
however, the very powerful prom ise of quantum  com puting will still have issues with photon 
loss in any solid state device. T he 4 0-year horizon will see photon technologies play an 
essential but supporting role in distributed quantum  com puting. Realized all-optical non­
quantum  system s will have radiation tolerance advantages over current sem iconductor 
technology and are likely to augm ent or even replace general-purpose com puting devices for 
space travel.
Hybrid designs utilizing arrays of quantum  dots and photon com m unication channels will be 
an option for space travel supercom puting on the 4 0-year tim escale. T hese system s operate 
at attainable tem peratures without cryonics, and require no m ore shielding than hum ans. It 
is likely that spintronics will be an essential ingredient.
Sim ple organic com puting based on D NA tiles will be realized in the next 20 years. O n the 
4 0-year tim e horizon, useful D NA-based devices will be essential space exploration tools. 
T hese could take the form  of orbital-delivered wireless sensors searching planetary/asteroid 
features or for essential com pounds such as high concentrations of water. D NA com puters 
will also be realized on the 4 0-year tim eline. T heir advantage over solid state devices will be 
the ability to repair nanoscale elem ents dam aged in norm al use or by cosm ic radiation.
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T hese will not be the fastest system s in the astro-arsenal, but self-repair m ay m ake them  
the m ost robust.
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INTRODUCTION
C om puters today are not what they used to be. In the 1 7th century, a com puter was m erely a 
person who perform s com putations. In this sense, the first com puters were universally 
program m able and were ultim ately utilizing organic (D NA) hardware architecture. T he 
m odern sense of a com puter as a m achine that m anipulates input to produce determ inistic 
output em erged from  the work of T uring in the 1 9 30s. A T uring m achine consists of four 
parts: tape containing cells of sym bols, read head, action table, and state register. In 
operation, the state register is initialized, the first cell of the tape is read by the head, the 
table translates the sym bol into an action in the state register, and the tape is advanced to 
read the next sym bol. T he read, action, advance tape loop is repeated until the program  
ends.(l) Any calculation a m odern digital com puter can perform  can be accom plished using a 
T uring m achine?
Modern digital processing hardware, first used in the ENIAC  in the 1 9 50s, is based on logic 
gates. All functions of a com puter consist of the basic logic elem ents AND , O R, NO T , etc. 
T hese are accom plished electronically by producing logic gates, com binations of transistors 
that perform  the logic function on input data. A com m on exercise in didactic digital logic 
pedagogy is to design all of the basic logic gates using only NAND  or NO R gates; thus, any 
hardware elem ent that can execute the NAND  function can build a com plete com puter?  
O ptim um  designs are regularly m ore elegant than com bining a single two-input gate, but it is 
sufficient as proof of principle for any architecture to be able to produce an inverter and a 
sim ple logic gate (AND /O R).
T he quest for faster com puting can be accom plished by m aking current hardware 
architecture faster, or by designing new hardware based on different architecture that solves 
the calculation in fewer steps. T he current treatise concentrates on the latter, dram atically 
changing the architecture of m odern com puters to perform  calculations in a different m anner. 
T wo m ethods are explored: that of creating logic gates, and that of creating a general T uring 
m achine. T he second of these is explored in the context of quantum  com puting with an 
em phasis on organic m olecules as a core technology. D esigns of logic gates utilizing D NA are 
covered. B ackground on all these areas of research is included first. Finally, D NA m achines 
that can assem ble and repair D NA technology are outlined.
ULTRAFAST COMPUTING POWER IN AEROSPACE 
APPLICATIONS
T he history of m anned spaceflight does not include powerful com puters as integrated 
com panions; space-borne supercom puters have so far been reserved to the world of science 
fiction. T he m ain issue on space stations has been radiation hardness, while the m ain issue 
on vehicles such as the space shuttle has been safety. T he am ount of testing required for a 
m icroprocessor to be certified for space precludes the m ost current technology from  
becom ing astro-worthy. Indeed, the m ost powerful general purpose com puters riding in the 
shuttle are the laptops the astronauts bring with them .
3 The complete history of computers up until the 1950s is a fascinating story. A good summary of this history is available 
in the Wikipedia entries for "computer" and "Turing machine" among other places. The model of a Turing machine 
presented is simplified.
bThe didactic exercise is usually followed by a laboratory exercise on breadboards and measurement of the truth table. 
NAND gates are popular because they are particularly simple to manufacture with current technology.
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T he first challenge to overcom e in supercom puting in space is radiation causing tem porary 
and perm anent errors in calculation. T he current approach is to m ake the solid state 
com ponents radiation-hard, a tim e-consum ing and costly process. An alternate approach is 
to use m ultiple com m ercial-off-the-shelf (C O T S) com ponents in parallel architecture.
George's group at the University of Florida pursued this approach with earthbound success. (2, 
3) A good question arises that if 50 years of space travel hasn't required one onboard 
supercom puter, why start now?  It seem s NASA asked this question as well and, after years 
of preparation, cancelled the space test of the technology in late 2009 .
Regardless of the need for current m issions, one can im agine m any future applications where 
it would be m ore convenient to data process on long space m issions without downloading 
data to Earth-based system  and uploading the results. T his is especially true for long- 
duration spaceflight where com m unication delays could be m inutes to hours (Mars ~1 3 
m inutes, Jupiter ~4 5 m inutes, and Neptune ~4 hours). Spacecraft active in the 4 0-year 
horizon will require supercom puting technology on-board to process all of the data to be 
acquired during flight. T his includes astronom ical data as well as ship and crew data.c 
Exam ple m issions include Mars with a goal to analyze the planet using thousands of sem i- 
autonom ous sensors or m illions of independent, wirelessly com m unicating nanom achines 
("m agic dust"). In such scenarios, it is not necessarily num bers that need lots of crunching, 
but algorithm s that need to be run on powerful system s that could be non-traditional in their 
design; for exam ple, m assively parallel.
MAKING DIGITAL CIRCUITS FASTER
In consideration of the underlying physics in the electrodynam ics of transistor operation, the 
scale of the constituent elem ents dom inates the type of analyses required. In the 
m acroscopic regim e, constituents are m easured in m icrons or larger, properties are 
dom inated by well-defined statistical averages in bulk m atter, and non-classical effects due 
to the underlying fact that all particles involved in the interactions are really fluctuations 
within a relativistic quantum  field can safely be ignored. For 4 0 years m aking a fast transistor 
was prim arily accom plished by avoiding saturation between states in an arrangem ent known 
as em itter coupled logic (EC L, pronounced "ek-el"). T he EC L fam ily of logic circuits could 
achieve sub-nanosecond switching tim es and dom inated the leading-edge of high-speed 
com puting up until the early 1 9 90s. T he drawback of EC L was that without reaching 
saturation, no depletion zone existed within the individual transistors and thus current flowed 
through m uch of the device hardware instead of the usual sm all leakage current associated 
with gates in a defined state. EC L's large current flow m akes cooling and power requirem ents 
challenging, especially for space-based platform s where heat dissipation is an issue.
Saturation technologies, prim arily MO SFET -based, surpassed the speed of high-current 
devices when the footprint of individual elem ents becam e sm all enough that a change 
between depletion states could be quickly stabilized, given the com parably slow drift 
velocities of prim ary charge carriers. T hese C MO S-fam ily technology devices are the current 
state-of-the-art in integrated circuits, and device speed increases, until recently, were 
dom inated by m aking the circuit elem ents sm aller (see below). Intel produces high volum e 
IC s with circuit elem ents size at 32 nm , and has dem onstrated m em ory elem ents in 22 nm
c The scenario of several massive data acquisition channels was presented at the Workshop for Technology Breakthroughs 
for Human Space Exploration, June 17th 2010, NASA Headquarters, Washington DC. Navigation is and will continue to be 
handled by traditional computing machines - it is only rocket science that needs to be solved for navigation purposes.
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pitch.d B y com parison, atom ic diam eters range from  around 0.1 nm  to 0.5 nm , with silicon 
~0.2 nm , or only a factor of 1 00 sm aller.
As circuit elem ents decrease in size, the num ber of atom s m aking up the bulk m aterials 
decreases and ignoring individual quantum  effects becom es problem atic. T his is the 
m esoscopic scale. At this size, quantum  effects can introduce noise into the circuit as the 
unpredictable6 nature of the underlying wave functions. O nce the circuit size shrinks to only a 
few atom s, quantum  effects will em erge from  the noise dom ain to dom inate the electrical 
behavior. It is thought that exploiting rather than avoiding quantum  phenom ena m ay prove 
useful in this regim e for inorganic technologies.
Following Moore's law, in less than 1 0 years inorganic circuit elem ents will be less than 5x5 
m olecules in 2-D  extent. (Molecular m achines built of organic com ponents, prim arily D IMA, 
are discussed in a later section.) Shrinking traditional silicon-based general-processing 
technology to this m icroscopic scale is one m otivation for developing new types of m achines 
based on quantum  phenom ena, but it is not the only one. Sm aller circuit elem ents decreased 
the settling tim e of transistors and thus gates on C PUs, allowing increasing clock speed (the 
C PU can execute the next instruction with shorter delay from  the last instruction). C PUs 
today get m ost of their perform ance with parallel architecture, executing several instructions 
at once in different pipelines. Using sm aller circuitry in general consum es less power, and 
this allows m ore parallel elem ents to be packed into a reasonable wattage package. T he 
m arch toward sm aller circuitry is continuing unabated so planning for the eventual quantum ­
dom inant characteristics is essential.
It is com m on to use the analogy of the laser to elucidate the application developm ents 
possible with quantum  com puting. In one sense, the laser is just another hardware 
technology that m akes light. Earlier light technologies include organic-fueled fire (~50,000 
B C ), incandescent bulbs (early 1 9 th c.), and fluorescent cham bers (m id- 1 9 th c.). T he light 
source to utilize is not governed by the highness of the technology, but by requirem ents of 
the application. O ne can read by laser light, but older and cheaper incandescent light will 
provide superior perceptible illum ination to a page. T raditional sem iconductor-based 
com puting is cheap and plenty powerful for controlling navigation or driving ship status 
displays.
T he laser analogy is further revealing in that it is quantum  effects producing a special kind of 
light that is coherent. C oherent light is single wavelength with all photons travelling in the 
sam e direction/T his coherence is a natural consequence of conservation of m om entum  in 
the absorption/em ission process. (4 ) C oherent light is very useful for som e applications that 
require low dispersion; for exam ple, bouncing a beam  off of a m irror on the m oon, or the 
m ore pedestrian pinpoint highlight of a projected PowerPoint presentation.
T he practical uses of the laser are not universally bigger or sm aller, faster or slower, or m ore 
or less energy efficient than the other hardware technologies that produce light, they are just 
different. Sim ilarly, when we think of what hardware and applications will arise for quantum  
com puting, they too are not necessarily bigger, sm aller, or faster than traditional m ethods; 
they are just different, and m any could not be accom plished with traditional technologies. (5)
d Pitch is the distance between repeat circuit elements. What is most interesting about the 22 nm technology is that it was 
produced with 192 nm lithography.
G At the mesoscopic scale, individual wave functions are not prepared a priori or controlled in their propagation. Some of 
the noise components are correlated.
f Laser light is actually very narrow bandwidth rather than single-valued.
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APPLICATIONS OF QUANTUM COMPUTERS
Although sm aller circuitry and supercom puting is a m otivator, the driving application behind 
quantum  com puting is cryptography. First, there is cracking cipher codes. T he vast m ajority 
of secured com m unications utilize a m ethod known as public-key cryptography. In this 
m ethod, the code is based on the prim e num ber factors of a very large integer which is 
publically available. T he private key is one of the integer factors and this allows the receiver 
of inform ation to decipher the code easily. T he strength of this technique is that traditional 
com puter algorithm s will take a long tim e to guess the correct factors of the public key, on 
the order of m onths.9 T raditional brute force m ethods require a num ber of steps that 
increase as an exponential function of the size of the public key. However, in 1 9 94 Shor 
presented a quantum  algorithm  that would only require a polynom ial num ber of steps, thus 
dram atically decreasing the required tim e to factor, assum ing a quantum  com puter would 
ever be physically realized. (6) T his speedup is prim arily due to the nature of quantum  
waves; specifically, they can follow several parallel paths instead of the usual stepwise 
procedural execution of instructions. T his acceleration by superposition concept is m ore 
easily understood in a random  search of data. C onsider an algorithm  that has a 50%  
probability to locate a specific phone num ber in a database of N phone num bers by a random  
search. T he procedural algorithm  on average will require 0.5/V  inquiries to locate the correct 
num ber. A quantum  algorithm  on the other hand can be devised that accum ulates 
inform ation by exam ining m ultiple num bers with each step. Such a schem e has been shown 
to reduce the num ber of exam inations required to V /V . (7, 8 ) T he superposition of states 
allows exam ination and processing of several tape cells sim ultaneously in a T uring-inspired 
m achine.
Second, there is quantum  com m unication. O nce public key encryption is easily broken by the 
quantum  com puter, a new cipher needs to replace it. T he canonical quantum  com m unication 
experim ent defines a sender, B ob, and a receiver, Alice. In m ost scenarios, Alice and B ob 
com m unicate over a distance using entangled particles and a traditional open line. T he open 
line relays inform ation about m easurem ent settings, but is useless to an observer without 
access to the entangled wave function (entanglem ent is discussed below, and the open line 
inform ation is an analogue to the public key of current ciphers). T he other advantage of this 
setup is that alm ost any disturbance in the com m unication line between Alice and B ob would 
destroy entanglem ent and thus the inform ation would be lost instead of intercepted. 
Additional archetypical participants in a com m unications experim ent/scenario follow the 
English alphabet: C harlie (or C huck if his intent is m alicious), D ave, Eve, etc. Quantum  
com m unication is thus an application replacing one perform ed by a general purpose 
com puting m achine; the classical and quantum  system s do not operate in sim ilar fashion 
other than the function of securely transm itting inform ation. Additionally, quantum  
com m unication has been suggested as a m ethod to connect isolated quantum  system s 
without disturbing closed box requirem ents like classical interventions would. (9 , 1 0)
B eyond cryptography is a third application, quantum  m etrology, where tim e and/or distance 
are m easured to an extrem ely high accuracy. A fourth obvious application is sim ulation of 
quantum  system s. (1 1 , 1 2)
9 Or hours if one has farms of supercomputers. The point is that the value of most communication is much smaller than 
the cost to decipher by brute force. The 128-bit web standard is a compromise between security and speed.
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THE CLOSED BOX AND FAULT TOLERANCE
In traditional silicon transistor circuits, once a bit is set to 1 or 0 by a gate or other device 
locking the output voltage, that value is expected to rem ain through subsequent clock cycles 
until determ inistically changed?  Additionally, traditional circuits behave by the sam e rules for 
each clock cycle; that is, as m ore inform ation is processed, repeated gate operation does not 
deteriorate the bit latching m echanism . T his behavior is achieved by constantly providing 
energy to the circuits. Any interruption in this constant need for power from  the outside and 
the integrity of the inform ation in the com puting circuit is lost.'
A fundam ental principle of quantum  m echanics is that any external influence on a system  
necessarily disturbs the state of that system . T his influence could be external disruption or 
internal leakage - either interaction will change the internal quantum  state. T his destructive 
process is known as decoherence. External influences will disturb the system  and thus the 
circuits need to be isolated from  the rest of the universe, also known as the 'closed box' 
requirem ent.
T rial to trial variations in a quantum  circuit produce an increasing deviation from  an initial 
phase as the wave function evolves. T his trial-to-trial deviation causes decoherence on a 
tim escale term ed T 2*. Although a single trial in a quantum  circuit could retain coherence 
longer than T 2*, absent external influence the isolated internal circuit com ponents m ust 
eventually com e to therm al equilibrium  through random  processes: this occurs on tim escale 
T l. Moreover, the closed box cannot be perfect since a useful device requires som e kind of 
input and output, thus som e sm all interaction with the external environm ent is necessary. 
Random  interactions with the environm ent from  this isolation 'leakage' will dephase internal 
signals on tim escale T 2. T hese three tim e constants that describe the internal signal decays 
are very sim ilar to the sam e nam ed quantities in nuclear m agnetic resonance (NMR). NMR is 
indeed a technology path under developm ent for quantum  circuits. Each technology and 
hardware design will be characterized in its isolation from  external and internal influences by 
T 2* (stable repeatability), T l (resistance to entropy), and T 2 (isolation from  the rest of the 
universe).
No design can be com pletely free of decoherence and the next consideration is how m uch 
decoherence is acceptable, or m ore precisely, what is the fault tolerance threshold for 
successful operation?  Fault tolerance isn't m uch of a consideration in traditional processing 
architecture/ although it is a m ajor consideration in storage and com m unication of 
inform ation. T o illustrate fault tolerance, consider a schem e of hard disk storage 
configuration where each 8 -bit byte is written across 9 disks in a stripe-set configuration 
(one bit per disk, read in parallel). T he extra disk holds parity inform ation about the byte. 
C onsecutive bytes shift the location of all bits one disk so the parity inform ation isn't all 
stored on the sam e disk?  In the event one disk fails, each byte can be reconstructed from  
the other 8 disks using a software algorithm  that autom atically starts when the disk failure is 
detected. T he broken hardware can be replaced and the data reconstructed while the system  
is operating in this slower 'lim p' m ode. T his storage system  is said to be fault tolerant. T he
h For those new to quantum phenomena, it may seem redundant to use the phrase "deterministically changed.'" The 
phrase emphasizes the point that absent any error, classical circuits are always changed by intent, while quantum circuits 
include the element of random occurrence.
' Here we refer to the processing circuits themselves. Some types of memory and long term storage can of course hold 
information in isolation indefinitely.
J A non-deterministic result in processing hardware causes a fatal error in current designs.
k The bitwise stripe-set is instructive on the principle at hand, but for engineering considerations, more complex 
configurations are used in practice. See Wikipedia "RAID" for actual data distribution schemes.
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drive failure detection and algorithm  takeover in the readout phase is the error correction 
schem e.
In a quantum  system  the error correction is accom plished in a sim ilar m anner; that is, the 
state of a qubit is defined across m ultiple subspaces of the logic space and then several 
m easurem ents are perform ed on the subspace that do not disturb the state itself. T he 
original state can be reconstructed by the partial m easurem ent. As an illustrative exam ple 
consider the one-qubit space defined by an electron spin-up or spin-down. First, re-define 
this 1 -d state in an oblique three-dim ensional system  such that spin-up is in the (+ x,+ y,+ z) 
octant, and spin down is thus in the (-x,-y,-z) octant. If one m easures x as positive the 
original state was up; m easuring x and y both positive provides additional assurance the 
state was actually up. Measuring x and y different allows z as a tie-breaker. In this exam ple 
system , 33%  error rates are allowed. O f course realizable system s are m ore com plex and 
only tolerate error rates in the 3%  range. T his difference is m ainly due to the need to disturb 
the system  as little as possible in what is known as a quantum  non-dem olition m easurem ent 
(a QND  m easurem ent). (1 3, 1 4) In sum m ary, fault tolerance is possible if a QND  m echanism  
to m easure qubits can be dem onstrated.
SCALABILITY
O nce a closed box has been constructed, the next consideration in successful quantum  
inform ation processing (Q IP) technology is whether circuit elem ents are scalable. T hat is, 
whether elem ents shown to perform  as quantum  bits can be com bined into larger circuits at 
a reasonable cost of resources (com putation tim e, decoherence tim e, physical space, or 
required power). T he exact nature of the required engineering scale-up is specific to each 
technology.
T he unit of Q IP (quantum  inform ation processing) is the qubit.1 D ifferent from  digital logic, 
quantum  m echanics increases the inform ation content in N qubits through superposition. 
T hat is, quantum  waves can travel through several paths and contain a superposition of 
states, increasing the am ount of inform ation in each channel. Furtherm ore, any system  of /V  
qubits can have degrees of entanglem ent. T his entanglem ent m akes the sim ple exam ple 
state (1 ,0,0) different from  (1 ,0,0) with (x,0,0) entangled, different from  (1 ,0,0) with (1 ,0,x) 
entangled, etc. W hen there are 4 qubits, entanglem ent can occur with 2, 3 or all 4 bits, as 
well as 2 with 2. T he logic space quickly grows to B unyanesque proportions and is easily 
outside of the realm  of sim ulation or even representation by N or even N 2 classical bits. 
C onsidering that one could start with qupits or qudits (see footnote I) it is quickly obvious 
that quantum  com puters have enorm ous com putational potential when scalable.
1 For pedagogy, the discussion is limited to qbits; however, p and d states could also be used as a basic unit (qpits or 
qdits) thus greatly expanding the possible information content in a single channel.
UNIVERSAL LOGIC
T he very large num ber of possible states of a quantum  com puter spans what is known in 
m athem atics as a Hilbert space, a generalized version of Euclidean space with arbitrary 
(finite or infinite) dim ension (Euclidean space having 3 dim ensions). T he concept of a 
universal logic requires that this large Hilbert space be accessible with a finite set of control 
operations. For m ost designs these control operations are sm all in num ber and are the 
quantum  analogues of digital gates perform ing operations on qubits.
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T wo special schem es that operate differently than digital analogues of gate-based technology 
are adiabatic and cluster-state quantum  com putation. In an adiabatic design, the answer is 
the ground state of a com plex network of interactions and the interactions are slowly turned 
on to evolve qubits from  the initial state to the final ground state. In the cluster-state 
schem e, the system  is placed in a particular state through use of a sm all set of control gates 
and the output is repeatedly m easured using arbitrary basis (the fault-tolerance m echanism ). 
In the adiabatic case, the com putation is 'program m ed' in the setup of interactions. In the 
cluster-state case, the calculation produces a superposition of states that need several 
m easurem ents to ensure correct interpretation. B oth schem es have been shown to be 
equivalent to gate-based circuit technologies. (1 5-1 7)
INITIALIZATION AND MEASUREMENT
Im plied in the discussions above is the ability to set the quantum  com puter into a known 
initial state, m easure various states during com putation if needed, and output the final state. 
T hese processes can be tricky while m aintaining isolation and low entropy. T he initialization 
and m easurem ent techniques are discussed with each technology.
The Quantum Dot Approach
A m ajor obstacle in the quest to design and construct a radically new kind of inorganic 
quantum  com puter has been finding a way to m anipulate the single electrons that are likely 
to constitute the new m achines' qubits. T he ability to m anipulate and alter a single electron 
without disturbing the trillions of electrons in the im m ediate surroundings has becom e a 
research focus for m any studies. (1 8 ) (1 9)(20) A candidate is to utilize properties of the 
intrinsic spin of the electron. In 1 925, Austrian physicist W olfgang Pauli proposed that an 
electron in a quantum  state can assum e only one of two states-"spin-up" or "spin down." 
(21 ) O ne approach to m anipulate spin state and electrical charge independently for use in 
quantum  com puting has arisen in the quantum  dot.
Q uantum  dots (QD s) are tiny islands within a solid state lattice where electrons experience 
charging effects as well as quantum  confinem ent, like an electron in an energy level around a 
nucleus. (22) B esides fundam ental insights into m atter, these artificial atom s can also work 
as building blocks for the control of electronics at the single electron level. T he so called 
single-electron transistors are able to switch on and off electron transport through a dot by 
m eans of electrical gates using the effect of C oulom b blockade.
C onversely, one can use spin rather than charge to control electrical conduction in 
m esoscopic-scale electronics; such "spin-controlled electronic devices," and their 
developm ent and study, are term ed spintronics. (23) Exploiting the spin degree of freedom , 
a quantum  dot can act as a spin filter (24 )(25)(26) or as a spin-blockade device. (27) 
Q uantum  dots have been proposed as host for an electron-spin qubit. Arrays of such 
quantum  dots with tunable tunnel-couplings between them  would work as a universal 
quantum  com puter. (28 ) Recent progress in this field using GaAs-based two-dim ensional 
electron gases is im pressive (29 ), though decoherence can arise from  spin-orbit and 
hyperfine interaction with the nuclear-spin(s) of the host m aterial (30) (31 ) (32). T hese 
decoherence effects can be reduced by using a lattice structure with low m agnetic m om ent. 
C arbon has near zero m agnetic m om ent due to the six each paired protons and neutrons in 
carbon isotope 1 2C ; a sm all net m agnetic m om ent com es from  the natural 1 %  contam ination 
of 1 3C .
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Electrostatic Quantum Dots in Graphene
T he graphene form  of carbon, a hexagonal sheet array single atom  thick, is a candidate 
substrate for quantum  dots. However, two fundam ental challenges need to be overcom e 
before graphene can be used to form  and operate spin qubits. First, it is difficult to create a 
tunable quantum  dot in graphene because of the absence of an energy gap in the band 
spectrum . Electrons in such low energy gap m aterials exhibit Klein tunneling, and 
com plicating efforts to confine particles (33) (34 ) (35). Second, due to the valley degeneracy 
that exists in graphene, (36)(37)(38) it is non-trivial to form  two-qubit gates using 
Heisenberg exchange coupling for spins in tunnel-coupled dots. Attem pts have been m ade to 
solve the first problem , such as to use suitable transverse states in graphene ribbons to 
confine electrons (39 ), to com bine single and bilayer regions of graphene (4 0), or to achieve 
confinem ent by using inhom ogeneous m agnetic fields. (4 1 ) T he second problem  has only 
been realized recently, and scientists have created a m ethod to confine the electrons in a 
unique valley through suitable transverse states in a ribbon of graphene which appears to 
overcom e these lim itations. (4 2) T he approach as used in GaAs quantum  dots (4 3) is not 
possible due to Klein tunneling.
Figure 1. Hexagonal structure of graphene.
Several ways are possible to induce a gap in bulk graphene. In general, quantum  
confinem ent can lead to the opening of a gap in ribbons (4 4 ) (4 5) (4 6). W ithin the tight- 
binding approxim ation of graphene, arm chair boundary conditions can lead to an insulator 
and gate-tunable quantum  dots (Figure 2).
Another prom ising direction is to start with bulk graphem e and induce a gap via the 
interaction with a substrate. (4 7)(48 )(4 9 ) T hree quantum  dot architectures that allow for 
bound states tunable by electrostatic fields are: (i) graphene nanoribbons with arm chair- 
term inated boundaries, (ii) discs in single-layer graphene, and (iii) discs in bilayer graphene. 
Special em phasis is given on the ability to controllably break the valley degeneracy, a 
prerequisite for two-qubit spintronic gates (50) (51 ) in graphene.
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Quantum Dots in Graphene Nanoribbons
Graphene ribbons are one dim ensional stripes of graphene. T hey can be considered as 
unfolded carbon nanotubes. Graphene ribbons were proposed by Nakada et al in 1 9 96 (52). 
Nakada used the sam e single orbital tight-binding m odel that successfully portrays two­
dim ensional graphene as a sem im etal; graphene ribbons are either m etallic or 
sem iconducting depending on their crystallographic orientation and width. More realistic 
calculations using the Hubbard m odel in a m ean field approxim ation and density functional 
calculations show that zigzag ribbons are insulating due to the m agnetization of their edges 
with opposite spin orientation in each edge. It has been found that this anti-ferrom agnetic 
insulator phase has a hidden underlying ferroelectric order that can be described as excitonic 
insulator whose order param eter is the spin-resolved dipole operator, the analog of the spin 
current operator (53). Long (gl pm ) graphene nanoconstrictions display gapped behavior: 
conduction is suppressed by several orders of m agnitude for a wide range of gate voltages 
around the D irac point, and for tens of m illivolts of source-drain bias (54 ) (55).
Figure 2. Quantum dot in graphene nanoribbon. A ribbon of graphene with semi-conducting 
armchair boundaries is schematically shown. Two barrier gates (blue) define the rectangular 
size of the quantum dot (with width W and length L). A back gate (red) allows one to shift the 
energy levels in the dot. Two or more quantum dots of this type can be easily put in series in a 
single nanoribbon.
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Figure 3. Left; Energy diagram for quantum dot in single-layer graphene. Right; Bound state 
levels as function of dot radius.
Graphene Disc in Single-Layer Graphene
Single layer graphene is attracting attention because its charge carriers are m assless, 
relativistic particles (56). T he relativistic effects result from  a unique, zero-gap band 
structure that leads to quantum  states described by the two-com ponent D irac-W eyl equation. 
T his allows relativistic physics to be explored in a solid state system  and has m any potential 
applications ranging from  high frequency electronics (57) to quantum  com puting (58).
Graphene dots can be form ed from  external potentials or nanocrystals but this work is only 
concerned with external potentials. T he physics of nanocrystals has been discussed recently 
(59 ) (60) and is different from  the situation treated here. T he quantum  states, in external 
potentials are quasi-bound: they have a low am plitude oscillatory tail and are sim ilar to the 
scattering resonances studied in undergraduate physics. A perpendicular m agnetic field 
enhances the localization of these states (61 ) and true bound states can occur in graphene 
dots defined by a spatially non-uniform  field (62). So a m agnetic vector potential has a 
localizing effect that tends to cancel the delocalizing effect of a scalar potential.
V a, [mV ] V 91 [mV ]
Figure 4. (a) Color scale plot of the transconductance, (b) One of the vertices of the honeycomb 
structure at Vsd = 800 pV: Charge stability diagrams for series-coupled quantum dots.
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Graphene Disc in Bilayer Graphene
B ilayer graphene is the two-layer analog of the single layer. T he two sublattices are coupled 
by the so-called B ernal stacking. A voltage V  between the two layers breaks inversion 
sym m etry (like the m ass term  △  in the single layer) and opens a gap proportional to the 
voltage. In addition, the com bination of a top gate and a back gate allows tuning the gap and 
the average potential U(r) independently.
A central issue, from  a com putational electronics perspective, is to quantitatively study the 
condensed state. In m aterials-based device m odels, one has an underlying Ham iltonian, such 
as an ab initio Ham iltonian.m
In principle, the excitonic condensate em erges from  the interacting particles described by the 
Ham iltonian. It is shown that both true bound states and quasi-bound states occur, 
depending on the form  of the potentials. In addition, there is a third and m ost interesting 
possibility where the character of the states depends on the param eters of the potentials and 
can be controlled at will. A confinem ent-de-confinem ent transition then occurs in which the 
character of the states changes from  oscillatory to exponential as in the Klein paradox for 
particles with m ass. T his gives a way of probing the Klein paradox experim entally in a solid 
state system  and num erical studies of the quantum  states in a realistic dot m odel show it is 
feasible. Further, the sam e effect could be used to fabricate a graphene dot which has true 
bound states. T his only requires a uniform  m agnetic field and a gate which can be m ade 
lithographically, a geom etry that is m uch easier to fabricate than the non-uniform  m agnetic 
field geom etry.
T he relativistic nature of the transm ission, exactly 1 00% , does not depend on E and U o is a 
consequence of the zero m ass. If the particles had m ass m o, the energy-m om entum  relation 
would be (E - I/)2 - p2c2 = m o2^ and the am plitudes of the wave function com ponents in 
equations of m otion would depend on k or k 1 and m o. T hen the right side am plitude in 
equations would be different from  the left side am plitude, so a reflected wave would have to 
be introduced to satisfy the boundary condition at x = 0 and the transm ission coefficient 
would not be 1 00% .
Figure 5. Quantum dot in bilayer graphene.
m Ab initio Hamiitonian is one derived from first principles.
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Figure 6. Bilayer graphene tunneling device structure. Two sheets of graphene 
are separated by a one-nanometer thick insulating of graphene.
Manipulation of Spin Qubits in Graphene Quantum Dots Relative to GaAs
For universal quantum  com puting, single-qubit and two-qubit m anipulations are necessary. 
Single-qubit rotations of spin qubits are naturally done by electron spin resonance (ESR) (63) 
and by electric- dipole-induced spin resonance (ED SR) (64 ). T he Rabi frequency fRabiat which 
the qubit rotates, for instance, in the ESR experim ent (65) is proportional to the electron spin 
g-factor, fRaw = gpB B ac/2h where ps is the B ohr m agneton and B ac the external oscillating 
m agnetic field used to rotate the spin. Notably, the electron spin g-factor differs for different 
m aterials. In GaAs quantum  dots, it has been m easured to be |g| <  0.4 3 (66) whereas, in 
graphene quantum  dots, it has been determ ined to be close to |g| = 2. (67) T hus, it is 
possible to rotate the electron spin in graphene quantum  dots using ESR about five tim es 
faster than in GaAs quantum  dots using the sam e field strength of the external oscillating 
m agnetic field. T his is an im portant gain because all qubit m anipulations need to be done 
fast to avoid decoherence and im plem ent fault-tolerant quantum  com puting (68 ).
Another im portant advantage of graphene spin qubits is related to the sm all band gap in 
graphene nanoribbons. (For a ribbon width of about 30nm , the band gap can be estim ated to 
be of the order of 60 m eV .) T his fact yields additional flexibility for two-qubit operations. 
T wo-qubit operations are usually done via the Heisenberg exchange interaction (69 ). T he 
tunneling m atrix elem ent can, however, be easily tuned by increasing or decreasing the 
overlap of the wave functions of the electrons in the two quantum  dots. In graphene or any 
sm all band gap sem iconductor, this m anipulation can be done in two distinct ways: either 
through tunneling via conduction band states (i.e., norm al tunneling) or through tunneling 
via valence band states (i.e., Klein tunneling). T his has been predicted for graphene 
nanoribbons and experim entally realized in carbon nanotube quantum  dots in (70)(71 ).
T he m ost im portant physical consequence of this additional flexibility is the appearance of a 
new type of long-distance coupling between graphene spin qubits as illustrated in Figure 8 .
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B y m eans of Klein tunneling, two distant qubits can be strongly coupled without touching the 
states of interm ediate qubits that m ight be located between the two. T hus, a ribbon of 
graphene hosting m any spin qubits in a line can be viewed as a qubit piano where any two of 
them  can be entangled with leaving the states of the others unchanged; see Figure 7. 
Interestingly, this feature, i.e., the availability of non-local interactions, is im portant for 
quantum  error correction since it raises the threshold for fault-tolerant quantum  com puting 
(72).
Figure 7. Qubit piano. Illustration of many spin qubits in a line hosted within a 
graphene nanoribbon. Quantum dots are red bars and barrier regions are blue 
bars. Different spin qubits that are strongly coupled to each other via Klein 
tunneling are marked with the same color.
Figure 8. Long distance coupling of three graphene qubits.
Spin Relaxation and De-phasing in Graphene Quantum Dots
W hy can we expect stable spin qubits in graphene quantum  dots?  T here is hope that spin 
relaxation and dephasing will be very weak in graphene for the following reasons: (i) C arbon
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is a light elem ent with atom ic num ber 6. Hence, its atom ic spin-orbit interaction is weak as 
com pared to heavier elem ents. However, such a statem ent should be taken with care 
because, in the solid state, spin-orbit coupling is oftentim es dom inated by bulk inversion or 
structure inversion asym m etry. T herefore, crystal structures of light elem ents can (under 
certain circum stances) exhibit rather strong spin-orbit coupling.
Prim e exam ples are carbon nanotubes where theory predicted a substantial spin-orbit 
coupling (a few hundred peV ) due to the curvature of the tube (73) (74 )(75) which has been 
nicely confirm ed in recent transport experim ents on carbon nanotube quantum  dots (76). 
Since the surface of graphene is less curved than that of carbon nanotubes, the spin-orbit 
coupling in graphene - due to ripples - should still be rather weak (roughly ten tim es less 
than the spin-orbit coupling due to curvature in carbon nanotubes (77)). (ii) C arbon has two 
stable isotopes: 1 2C  and 1 3C . T he natural abundance is 9 9 %  1 2C  and 1 %  1 3C . Since 1 2C  
has nuclear-spin 0 and 1 3C  has nuclear-spin 1 /2, the electron spin of the qubit can only 
interact with 1 %  of the nuclei via hyperfine interaction. T his ratio can even be further 
decreased because it is possible to artificially m ake 1 2C -enriched graphene.
Spin Relaxation Due to Spin-orbit Interaction
T he spin-orbit coupling arises from  the band structure and is enhanced by ripples in the 
graphene sheet. T he orbital m otion is influenced by scattering centers and ripple-induced 
gauge fields. Spin relaxation due to Elliot-Yafet and D yakonov-Perel m echanism s and gauge 
fields in com bination with spin-orbit coupling are discussed. In intrinsic graphene, the 
D yakonov-Perel m echanism  and spin flip due to gauge fields dom inate and the spin-flip 
relaxation tim e is inversely proportional to the elastic scattering tim e. T he spin-relaxation 
anisotropy depends on an intricate com petition between these m echanism s.
As Pauli noted, when an electron is in a quantum  state it can sim ultaneously be partially in 
the spin up state and partially in the spin down state. D uring this phenom enon known as 
"superposition states" an electron can exist in a free spin cycle oscillating between the up 
and down states. A qubit based on the spin of an electron could have nearly lim itless 
potential because it is neither strictly on or off. Recently, researchers at Princeton University 
discovered how to m anipulate a single electron without disrupting any surrounding electrons 
(78 ). B y utilizing an interferom eter technique where one or two electrons are trapped in 
m icroscopic corrals that are created by applying voltage to m iniscule electrodes, "spin qubits" 
were form ed. T his effort is ground-breaking in that previous research utilized techniques 
where the electrons were exposed to m icrowave radiation.
T he previous m ethod was ineffective to m anipulate individual spin qubits because the 
m icrowave was incapable of isolating to only a single electron. W hereas com m only used 
single-spin rotation m echanism s rely on gigahertz frequency m agnetic fields, the coherent 
rotations between S and T + dem onstrated here occur on a nanosecond tim e scale set by the 
Zeem an energy and are solely driven with local gate-voltage pulses. As a result, it will be 
feasible to scale this quantum  control m ethod to a large num ber of spin qubits operating in 
close proxim ity. In addition, it is possible that the spin-flip m echanism  em ployed here, which 
relies on coupling to the nuclear-spin bath, could be harnessed under the appropriate 
conditions to create a nuclear-spin m em ory (79 ).
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Research with Graphene Quantum Dots
Graphene is an ideal candidate for spin qubits due to its low intrinsic spin-orbit coupling and 
the sparse am ount of nuclear spins. W e discussed bound states in gate-tunable graphene 
quantum  dots realized in both graphene nanoribbons and gapped single-layer and bilayer 
graphene. In contrast to quantum  dots realized in edged graphene flakes, gate-tunable 
quantum  dots are defined electrostatically rather than by the physical edge of a graphene 
sam ple. T his allows one to controllably break the valley degeneracy, a prerequisite for spin­
based quantum  com puting, e.g., by using a m agnetic field. W e have also discussed quantum  
m anipulation of spin qubits in such dots, as well as recent theoretical studies on the 
consequences of spin-orbit interaction and hyperfine interaction with nuclei for spin­
relaxation and spin-decoherence. B oth theoretical and experim ental efforts have focused on 
single-layer graphene quantum  dots. T he next m ajor area is likely to be bilayer graphene. 
B ilayer graphene is potentially superior to single-layer graphene due to the creation of a 
tunable bandgap by electric fields which allows for an all electrical control of graphene 
quantum  dots.
T hese new capabilities m ay be a boon for spintronic quantum  inform ation processing. 
Single-qubit gates, based on single-spin electron spin resonance, have achieved significant 
breakthroughs. Fast (~200 ps) two-qubit operation has been dem onstrated, but single-qubit 
operations on a sim ilar tim e scale still rem ain a challenge. A proposed new configuration of 
two-spin encoding of the qubit, where a single and a triplet state play the role of the 0 and 1 , 
shows prom ise. W ith this type of qubit, the interferom eter, dem onstrated by the Princeton 
researchers, could be used for single-qubit gates on a nanosecond tim e scale. Alternatively, 
fast qubit rotations in a slightly different singlet-triplet qubit can be obtained by aligning 
nuclear spins to create different nuclear polarizations in the two dots. Fast single-qubit and 
two-qubit gates available in the sam e system  allow for efficient quantum  error correction and 
could provide an im portant head start in the battle against decoherence. However, no two- 
qubit gates for this type of qubit, which would involve four spins, have yet been 
dem onstrated. Utilizing graphene as a structural basis for quantum  com puting, coupled with 
other carbon based m aterials such as self-assem bling D NA, m otifs, m ay lead the 
revolutionary developm ent in quantum  com puting.
SUMMARY OF ADDITIONAL INORGANIC TECHNOLOGIES
T he advancem ent of quantum  com puting schem es is the subject of significant investm ent 
and developm ent over the past two decades. Recently, Ladd reviewed inorganic technologies. 
(5) Ladd proposes that ion traps are the m ost probable technology based on their long T 2, 
but then concludes that a com parison between the technologies is incom plete without further 
developm ent on all fronts. T he current treatise concentrates on organic technology but 
sum m arizes here the work of Ladd and others for com pleteness.
Photon Technologies
Using the polarization state of a photon is an appealing approach to store, com m unicate, and 
m anipulate qubits. Photons do not require a vacuum  or very low tem perature for fairly good 
isolation from  therm odynam ic interactions. T hey do require special, non-linear m edia for 
robust, reliably predictable m anipulation. A m ajor advance in 2001, known as the KLM 
schem e, showed that a scalable quantum  com puting was possible using linear optics and 
single-photon detectors and sources. (8 0) T he m ajor hurdle, according to Ladd, is photon
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loss within waveguides, and is equivalent to decoherence tim e in other quantum  hardware.n 
T he size of quantum  gates is currently on the order of cm ; this hurdle becom es less as gate 
size decreases. It is finally concluded that photons will likely be used in a hybrid technology 
with another quantum  elem ent serving as the basis for gates and other interactions. T his 
schem e is known as distributed quantum  com puting, where elem ents can be separated by 
significant distance. T his distance is either large by com parison with gate or gate array size, 
or actually large (km ) in a com m unications network.
Photonic technologies are a very active developm ent area: the raw num ber of publications 
found for "photon com puters" or "photon com puting" shows m ore entries for 2009 than for 
2008 and 2007 com bined.0 Furtherm ore, m any devices operate at or near room  tem perature 
and m ost do not require expensive cryogenic system s (tem perature below He boiling point), 
m aking them  inexpensive to research versus other technologies. T hese objective m easures 
m ake breakthroughs m ore likely, and in 1 0 years all-optical com puting should be addressing 
problem s that cannot be accom plished via classical system s. In 4 0 years, m anufacturing 
engineering will decrease the cost of these devices and they will be an option for m any 
com puting tasks in the space environm ent.
Ion and Atomic Trap Technologies
Individual atom ic ions can be trapped in free space by nanoscale electrodes, while atom s can 
be trapped in an optical lattice created by lasers. In the ion system s, m anipulation of 
electrode voltages m ove ions around the lattice and interact them  with each other. In atom ic 
system s, m odulation of the optical lattice and/or external optical interference is used to 
m anipulate the atom s. Ladd concludes that scaling is the prim ary hurdle in trap-based 
technologies.
More detail of such hurdles in trap technologies is revealed in a year earlier (m uch longer) 
review by Haffner. (8 1 ) lon-trap-based gate operations are shown to have arbitrarily high 
fidelity, or higher fidelity than required for fault-tolerant com putation. T he current bottleneck 
in trap technology versus classical system s is the trapping frequency of a few hundred 
m icroseconds, even though m assive parallel operations are possible. Haffner concludes that 
there are no fundam ental barriers to scaling trap-based com puting, but the technology is 
challenging and will progress as evolution rather than revolution. T his is encouraging given 
that 4 0 years ago 20-nm  transistors seem ed challenging, but without fundam ental 
operational barriers.
Nuclear Magnetic Resonance (NMR) Technologies
NMR storage and m anipulation has been shown in liquid m edia up to a dozen qubits. Liquids 
are preferred because of their longer T 2. However, therm al m otion in the liquid state m ade 
scalability an issue. Moving to solid state NMR to address therm odynam ic issues dram atically 
decreases T 2. Ladd concludes that NMR technologies are a good testing ground for fault- 
tolerant algorithm  developm ent, but of little practical use for quantum  com puting.
Superconducting Technologies
Superconductivity is the flow of electricity without resistive losses. Sim ilar to the laser, this 
m acroscopic phenom enon has quantum  m echanical origins. W hen cooled below a critical
n A waveguide is the equivalent "wire" that isolates the transmission of photons between interaction and storage devices. 
° Web of Science database, inquired 30 June 2010.
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tem perature, som e m aterials such as copper form  a lattice that allows electrons to pair and 
flow as a bosonic charged (2e) particle. T he com ponents of superconducting circuits can be 
fabricated with current technology; however, decoherence tim es are lim ited to several 
m icroseconds m axim um  due to the large size (1 00 m icrom eters) of the circuit elem ents and 
thus large num ber of charge carriers in a qubit device (~1 01 0). Additionally, the current qubit 
device designs only operate at the scale of 1 0's of m K. Superconducting elem ents, 
specifically Josephson junctions, m ay play a role in hybrid designs such as the distributed ion 
traps of Haffner (8 1), but are currently not seen as a stand-alone technology for quantum  
com putation.
DNA-BASED DESIGNS FOR MOLECULAR COMPUTERS
W hile traditional silicon-based circuits reach their fundam ental atom ic lim itation, researchers 
search for alternative m edium s for com putation. T he m ost logical solution to overcom e this 
restriction in silicon-based integrated circuit architectures resides within our own bodies, 
deoxyribonucleic acid (D NA). Living organism s also carry out com plex physical processes 
under the direction of digital inform ation. B iochem ical reactions and ultim ately an entire 
organism 's operation are ruled by instructions stored in its genom e, encoded in sequences of 
nucleic acids. W hen the workings of bim olecular m achines inside cells that process D NA and 
RNA are com pared to T uring's m achine, striking sim ilarities em erge: both system s process 
inform ation stored in a string of sym bols taken from  a fixed alphabet, and both operate by 
m oving step by step along those strings, m odifying or adding sym bols according to a given 
set of rules.
Figure 9. A DNA nanomachine driven by repeated sequential addition of DNA control strands (82).
DNA Background
W atson and C rick m ay have never realized the full potential of the double helical structure 
they identified nearly 60 years ago, (8 3) for little was known about this am azing m olecule 
that harnesses life. B iochem ists in the late nineteenth century had found that these nucleic 
acids, long-chain polym ers of nucleotides, were m ade up of sugar, phosphoric acid, and
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several nitrogen-containing bases consisting of deoxyribonucleic acid (D NA). B y the late 
1 9 40s the scientific com m unity widely accepted D NA as the carrier of genetic inform ation. 
B ut, it wasn't until 1 9 77 that Fred Sanger developed the first dideoxynucleotide chain 
term ination bottom  up assem bly m ethod for D NA. (8 4 ) T his technique would later usher in a 
new age of nucleic acid research and open the door for the m odern era of biotechnology. 
W ith the advent of the Polym erase C hain Reaction (PC R) (8 5) technology a virtual treasure 
trove of capabilities now exist for genetic and biochem ical engineers to create custom ized 
D NA strands. T his revolutionary process has created a m ultidisciplinary field of work within 
nanotechnology that intersects at the crossroads of com puter science, biochem istry, m aterial 
science, and engineering. T his section on D NA-based nanosystem s and com puting will 
introduce several state of the art research applications and concepts currently being 
em ployed to produce D NA-based devices.
It is crucial to form ulate a basic understanding of the structure and chem ical principles of the 
D NA m olecule to fully grasp its potential as a building m aterial for D NA-based nanosytem s. 
For the lay reader we have constructed a sim plistic outline to illustrate the general principles 
of the D NA m olecule that hold true to their biochem ical properties as they apply to bottom - 
up nanostructure assem blies.
1 . D NA consists of two long polym ers m ade of sim ple units called nucleotides, with 
backbones m ade of sugars and phosphate groups joined by ester bonds. T hese two 
strands run in opposite directions to each other and are therefore anti-parallel. T he 
double strands of D NA form  a double helical structure.
2. T he inform ation in D NA is stored as a code m ade up of four chem ical bases: adenine (A), 
guanine (G), cytosine (C ), and thym ine (T ). T he order, or sequence, of these bases 
determ ines the inform ation available for building and m aintaining an organism . T hese 
nucleotides bind through a chem ical bonding process known as W atson and C rick base 
pairing. A bonds with T , and G bonds with C  - a given sequence of such nucleotides will 
always bond with the com plem entary sequence.p
3. In its double helical configuration, D NA is a relatively rigid m olecule. T his rigidity can be 
further enhanced by bundling several double helixes to form  D NA lattices and tiles to 
form  synthesized nanoarchitechtures (8 7)(88 )(8 9).
4 . T he W atson and C rick base-pairing principles have created predictable binding affinities in 
bench top applications. T his knowledge of the intra- and inter-m olecular physical 
properties of the D NA m olecule enable the program m ing of desired interactions within the 
sequences to produce a custom ized sequence of D NA.
5. T he ease in sequencing D NA based on the Sanger technique, which today has evolved 
into advanced autom ated processes, have m ade designer D NA strands readily available. 
C ustom ized strand lengths or oligonucleotides (strands typically 1 00-200 base pairs long) 
can be easily ordered from  various sequencing services or produced within the lab at 
relatively low costs with high throughput and quality.
6. T oday biotechnologists can em ploy a library of unique restriction enzym es that can cut 
the D NA strand between specific nucleotides leaving "sticky ends", or single stranded
p Sometimes transcription errors will result in an incorrect bond, such as A with G. These are single nucleotide 
polymorphisms, or SNPs (pronounced "snips"). SNPs are not uncommon in the human genome and have important 
implications in disease; however, in the current treatise we consider such "wrong" pairings to be errors that need 
correction.
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overhangs at the end of the double helix (Figure 1 0). T hese fragm ents can be exploited to 
create a recom binant m olecule of D NA by;
a. Inserting or rem oving a specific sequence of D NA.
b. Attaching a fluorescent m olecular beacon.
c. Am plifying the sequence through the PC R process.
5'________________G AAT T C__________________3*
3' CT T AAG  _____ 5'O riginal DN A 
molecules
Q Cleave DM As from two sources 
with same restriction enzyme.
O  M ix fragments and allow 
sticky ends to J oin by base pairing.
Figure 10. Recombinant DNA molecule with restriction enzyme cleavage and sticky end ligation.
7. B y carefully using the recom binant tools and technologies available to genetic engineers, 
one can properly program  a custom ized W atson-C rick base-paired D NA m otif that will 
self-assem ble in solution. T his m ethod of self assem bly is preferred on sm all scale 
applications due to the difficulties experienced when assem bling nanoscale objects 
through the traditional top down m ethod. Assem bly of D NA m otifs with the aid of various 
branched D NA strands with sticky ends can be directed by the geom etry and connectivity 
of the varying m otifs. O nce the structure is assem bled a range of D NA lattices can be 
produced (Figure 1 1).
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Figure 11. Two symmetric DNA nanomotifs and the crystals grown using them, (a) 
and (d) show a symmetric cross motif and a three-point-star motif, respectively. 
Images (b) and (e) are atomic force micrographs showing the crystal structure, 
and (c) and (f) are fluorescence microscopy images of DNA 2D crystals assembled 
from the DNA motifs (86).
8 . Another widely accepted bottom  up m ethod to construct D NA nanosystem s is through a 
process known as strand displacem ent or branched m igration. T his assem bly m ethod 
displaces one D NA strand and selectively replaces it with a strong com plem entary strand 
which usually consists of m ore W atson C rick base pairs. T his m ethod can be utilized to 
correct sequence errors m ade during strand synthesis and D NA tile assem bly and in 
com plex logic gates, and for controlling D NA m otors.
In 1 9 96, W infree devised a theoretical proposal that addressed how crystal m orphology and 
patterning can be program m ed by tile design in an inherently asynchronous assem bly 
process, in which it was addressed by the abstract T ile Assem bly Model (aT AM). (9 0) W infree 
explored how physical param eters, such as tile concentration and tem perature, affect crystal 
growth and influence error rates, based on reversible tile association and dissociation rates 
(9 1 ). T his work was built on previous efforts by W ang's (9 2)(9 3) em bedding of com putation 
in geom etrical tiles showing that two-dim ensional (2D ) self-assem bly of D NA can perform  
T uring-universal com putation. T his im plies that any algorithm  can in principle be em bedded 
in, and guide, a potentially aperiodic crystallization process. In this "algorithm ic self­
assem bly" paradigm , a set of m olecular "W ang tiles" is viewed as the program  for a 
particular com putation or m olecular fabrication task.
Later collaboration between W infree and Seem an resulted in the first successful fabrication of 
a two-dim ensional D NA lattice structure that utilized the m athem atical principle of tiling (9 4 ). 
T he self nam ed D X (double crossover) m olecule has two double helical m otifs that are rigidly 
bound together by several single strands that are organized in a double crossover pattern 
form ing a rigid structure of D NA. T hese D NA strands are oriented in a parallel direction. T his 
m ethod allows for the production of D NA based lattices by exploiting the use of sticky ends at 
four ends. T hese ends can then be further constructed to build up a scaffold of D NA based on
26
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the com plem entary binding of the W atson-C rick base pairs that correspond to each sticky 
end. In this way, a lattice structure can be built upon the base structure by synthesizing 
additional D X m otifs to construct what is known as a "D NA tile." T hese tiles can be further 
utilized as a scaffold for additional m olecular structures.
In order to envision the aT AM tiling process, it is easy to picture various tiles with different 
num bers written on the sides, indicating m atching rules where two tiles would stick only if 
their contacts m atched. Additional m atching interactions can be arranged in a m anner that 
adjacent tiles can strongly hold the next one in place, but a single interaction creates a weak 
bond. Figure 1 2 illustrates an instantiation of the algorithm ic self assem bly process, in which 
sets of four species tiles that represents XO R (exclusive O R) function to create a Sierpinski 
triangle pattern. T he so called seed structure is used to input the initial values that 
com m ence the algorithm ic self assem bly process. However, it m ust be noted that random  
nucleation events m ay occur. Nevertheless, algorithm ic self-assem bly has created a m eans 
to em ulate cellular autom ata.
Figure 12. (top a-e) The XOR Cellular Automaton and Its Implementation by Tile-Based Self-Assembly, 
(bottom a-e) AFM Images of Algorithmic Self-assembly of Sierpinski Triangle Crystals.
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Figure 12 (continued). (top a-e) The XOR Cellular Automaton and Its 
Implementation by Tile-Based Self-Assembly, (bottom a-e) AFM Images of 
Algorithmic Self-assembly of Sierpinski Triangle Crystals.
In theory, this process allows scientists the ability to build a com puter from  nanoscale 
m aterial with D NA tiles (9 5). T he experim ental success of this trial dem onstrated that 2D  
algorithm ic self-assem bly offers new capabilities for com putation and construction, as well as 
a new range of physical phenom ena and experim ental challenges as well.
Error Suppression Mechanisms in DNA Self-Assembly
Molecular self-assem bly is an em erging technology that will ultim ately enable the fabrication 
of great quantities of com plex nanoscale objects such as com puter circuits at very low costs. 
B ecause the D NA-tile-based bottom -up assem bly technique relies on the logic of 
program m ing self-assem bly, it requires a situation where sticky-end binding specificity is 
infallible. Realistically, however, correctness of m atching between tiles cannot be guaranteed 
due to the therm odynam ics and kinetics of D NA tile self-assem bly. T his process alone results 
in occasional erroneous assem bly steps. T he num ber of assem bly errors increases with the 
num ber of tile types, and accruing errors render large scale com plex com putation practically 
infeasible.
Assem bly errors can be classified into three types: 1 .) Growth errors. 2.) Facet errors. 3.) 
Nucleation errors. Growth and facet errors are the errors that occur on the growth front of an 
existing assem bly, while nucleation errors deal with the spurious initiation of assem blies. A 
growth error occurs when a D NA tile with one or m ore m ism atched sticky ends is em bedded 
in the assem bly. A facet error occurs on the flat surface (facet) of the aggregate when two 
D NA tiles attach on a growth front (facet) side by side, and thus stabilize each other's 
binding. T his is considered an error because the identity of these tiles m ay not be correct 
with respect to the com putation being perform ed. Nucleation errors are sim ilar to facet errors 
in that a num ber of tiles spontaneously assem ble a cluster by stabilizing each other through
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binding. T his then seeds ordinary, but m eaningless com putation. Growth errors, facet errors, 
and nucleation errors all occur because of tiles that m ake only weak contacts with the 
assem bly (Figure 1 5). T hese erroneous tiles m ust fall off in order for correct growth to 
proceed. O ne approach is to design the lattice such that each tile is first stabilized by the 
arrival of another tile before it secures itself in place.
Prior analysis predicted that the error rates of tile assem bly can be reduced by optim izing 
physical param eters such as tile concentrations and tem perature. In order to suppress 
different types of errors, several m ethods have been proposed based on the idea of 
increasing the am ount of tim e required to lock in erroneously assem bled tiles. In order to 
m inim ize the errors, several m ethods have been proposed. Unfortunately, som e of these 
m ethods cannot effectively suppress all types of errors. For exam ple, the tile proof reading 
m odel first proposed by W infree and B ekbolatov (9 6) can correct errors in growth if an 
incorrect tile attaches in the next position. T his error correction technique uses redundancy 
to correct errors. In this m ethod, each tile is replaced in the system  with four tiles, arranged 
in a 2 X 2 block. T he com pact resilient tile m odel as proposed by Reif (9 7) attem pts to 
reduce the increase in scale of the final pattern produced by self-assem bly. W hile both of 
these m ethods are effective in reducing errors, they are only lim ited to those errors produced 
by growth. However, the error suppression m odels Protected Tile M echanism  (PT M) and 
Layered Tile M echanism  (LT M) proposed by Fujibayashi and Murata can suppress all three 
error types illustrated in Figure 1 5. (9 8)(99 ). T he functional m ethod of suppression in these 
m odels is the control of sticky end hybridization. In these m echanism s the im plem entation of 
the D NA tiles is altered by the introduction of a structural m otif protection strand and 
protection tiles (see Figure 1 3 and Figure 1 4 ). In this technique, the protection strand is a 
single oligom er that covers the input side of the tile. Each sticky end rem ains uncovered and 
it works as the toehold for initiating a branch m igration process that rem oves the protection 
strand. T he com bination of a tile and a protection strand is called a "protected tile," or just 
"tile" when it is clear from  context, and "foundation tile" refers to the unprotected 
foundation tile. T he output sides of all tiles are unprotected, thus the growth front always 
displays unprotected sticky ends. As seen in Figure 1 3 the protected tiles associate to the 
growth front by the exposed 3-nt sticky ends first, then branch m igration results in strand 
displacem ent on each of the m atching input arm s; if both arm s are m atched, the protection 
strand is com pletely displaced, and it dissociates. In Figure 1 4, this m ethod undergoes Monte 
C arlo sim ulation to evaluate its suppressive properties. Surprisingly, it was discovered that 
the PT M and LT M suppression m ethods can prevent nucleation errors as well as growth and 
facet errors.
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l® l O utputs ^^ W
Inputs
Figure 13. Error Suppression with the PTM Method.
(al *=^=£f*>>» (b) ' - %T  ■ M *0 M  (c) r-%^-jH“"M
Figure 14. Simulation results of growth in (A) the OTM, (B) the PTM, and (C) the LTM.
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Figure 15. Three Types of Error in DNA Tile Self-assembly (a) 
Growth error (b) Facet error (c) Nucleation error. Red lines 
indicate the mismatched sides.
Self-assembly with DNA-based Microfluidic Devices
T hus far we have explored D NA com puting through m ethods based on linear D NA m olecule 
hybridizations (1 00) and "D NA tiles" with four "sticky ends"(1 01 ), W hile it has been proven 
experim entally that D NA tiles have m uch stronger com putational power com pared to linear 
D NA strands (1 02)(1 03), the suppression of assem bly errors is the central problem  of the 
D NA-tile-based nanotechnology. Even though several error reduction m ethods have been 
proposed thus far, m any of them  only consider the design of D NA tile sets. (1 04 ) 
T raditionally, the result is a com plicated tile set and these approaches are rarely 
im plem ented. T o overcom e these restraints, researchers in T okyo devised a m icrofluidic 
device specially designed for D NA tile assem bly (1 05).
T raditional D NA T ile assem bly m ethods require that all the D NA tiles are m ixed in a single 
test tube, annealed for self-assem bly, and then the m ixture is dropped on a m ica surface for 
AFM observation. Since all kinds of tiles are assem bled in one pot, D NA tile sets m ust be very 
carefully designed such that each sticky end has an appropriate bonding specificity and 
strength to obtain desired structure. In practice, it is very difficult to keep concentrations of 
each m onom er tile in one-pot self-assem bly. Additionally, the assem bly process is strongly 
affected by the concentration of the D NA tile and the tem perature of the water solution.
W ith the m icrofluidic D NA tile self-assem bler, a series of stepwise assem bly processes are 
incorporated into construction of the tile lattice. In the m icrofluidic device, pre-assem bled 
D NA lattices are anchored on the m icrofluidic channel to initiate tile growth through the 
following steps: 1 ) Single-strand D NAs are im m obilized on the surface of a reaction cham ber. 
T his provides scaffolds to initiate the self-assem bly process, while anchoring the assem bled 
structure against the flow. 2) Monom er D NA tiles are supplied by flow in the m icrochannel. A
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constant concentration around the crystal can easily be realized by a constant flow. T his 
ground-breaking work in D NA synthesis technology has opened the door for several 
applications in genetic engineering and lab on a chip technology (1 07)(1 08)(1 09).
T his kind of controlled self-assem bly will drastically im prove the size and yield of errorless 
nano structure. It is also possible to produce desired nano structures on a patterned 
tem plate in the reaction cham ber for various applications.
Figure 16. Micro-fluidic device for DNA tile self-assembly.
DNA Origami
T he idea of holding helical dom ains in a parallel arrangem ent via the juxtaposition of 
antiparallel crossovers has becom e a general principle in D NA nanotechnology, used in at 
least a dozen constructions. For exam ple, it has been extended to m olecules with three 
parallel helixes (1 1 0) and it has been used to attach triangles rigidly to a nanom echanical 
device. (Ill) However, these techniques do not create a generalized m ulti-crossover 
m olecule with parallel helices due to the inability to have the ratio of the com ponent short 
strands exactly equal.
Single-stranded origam i such as W illiam  Shih's octahedron (1 1 3) cannot, by definition, suffer 
from  this problem . Scaffolded origam i sidesteps the problem  of equalizing strand ratios by 
allowing an excess of helpers to be used. As long as each scaffold strand gets one of each 
helper, all scaffolds m ay fold correctly (som e m ight get trapped in m isfolding). B ecause 
origam i are easily differentiable from  the helpers, separating them  is not difficult (e.g. large 
origam i stick m uch m ore strongly to m ica surfaces than do tiny helpers and so excess 
helpers can be washed away). Single-stranded origam i and scaffolded origam i thus seem  
the best candidates for the creation of large com plex structures. As Shih has observed, the 
geom etry used for the octahedron should generalize and allow the creation of arbitrary 
polygonal networks. Generalization of the parallel helical geom etry introduced by double­
crossover m olecules is sim ple using scaffolded D NA origam i; Ruthem ond has recently 
dem onstrated the technique for the creation of six arbitrary shapes and six arbitrary patterns 
(including the one shown here); the design m ethod and experim ents showing its generality 
are described in (1 1 4 ). T o get a feeling for the m ethod, look at Figure 1 8 . Shapes are 
approxim ated by laying down a series of parallel helical dom ains inside of the shape (Figure 
1 8 a). Helices are cut to fit the shape, in a series of sequential pairs from  top to bottom , so
32
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that the resulting geom etry approxim ates the shape within one D NA turn (~ 3.6 nm ) in the 
x-direction and two helical widths (~ 6 nm , including an inter-helix gap) in the y-direction. 
T o m ake a m olecular design, a scaffold is run exactly once through each helix; perform ed in 
a raster-fill m anner, this creates a 'folding path' (Figure 1 8b). T o hold the scaffold in this 
shape, helper strands are added to create a regular pattern of antiparallel crossovers (Figure 
1 8 c).
Figure 1 9 illustrates the versatility of shapes-program m ed D NA origam i with a high yield in 
excess of 70% . Each shape seen in Figure 1 9 uses 7000-base long scaffolds requiring m ore 
than 200 D NA strands for a final m olecular weight of 1 5,000 nucleotides. T hus, the D NA 
origam i structure has a m olecular weight that is 1 00X that of the original D X m odel and 
nearly 6X larger in geom etric construction where 50 billion copies of the pattern are created 
at once. W ith this technique, a device has been created that has a m olecular weight of the 
com ponent of cells that can synthesize proteins and am ino acids- the ribosom e. For the first 
tim e, we are now capable of self-assem bling structures whose size and com plexity rival that 
of Nature's m ost com plex self assem bled m achines.
Reagent Controller Herringbone Binary T ree Column Array individually 
□ addressable
M d wive
Figure 17. (A) Schematic diagram of a 16-column microfluidic DNA synthesizer. 
The control lines are shown in red, the fluidic lines in blue, the herringbone 
mixers in yellow, and the square profiled binary tree and reactor columns in 
green. (B) Close up schematic of the column array (106).
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Figure 18. Design of DNA origami. (112)
Figure 19. Several DNA origami folding paths. (112)
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Engineering DNA-Based Logic Gates
T his branch of nanotechnology em ploys D NA enzym ology to induce m olecular behavior in 
solution that responds to an appropriate nucleic acid input. T he goal is to m ake reliable D NA- 
based logic gates that can be used to assem ble com plicated logic circuits, which, in turn, can 
be used to control com plex m olecular devices (1 15). Strictly speaking the silicom im etic 
solution-phase approaches are not connected to traditional D NA nanotechnology, or 
Adlem an's m odel of D NA com puting (1 1 6). However, there is som e overlap of concepts, and 
all these approaches can be integrated in order to achieve com plex functional behaviors. 
T here are two prim ary requirem ents that a D NA-based logical device has to fulfill: first, the 
device should have the ability to integrate the presence or absence of several inputs into a 
single output. Second, a device has to be designed in such a way that a lim ited num ber of 
sim ple devices can be com bined into a variety of com plex circuitries. T his usually m eans that 
one device can com m unicate with other com ponents through som e kind of inform ation 
transfer. Furtherm ore, devices that could com m unicate with sensors, and produce outputs 
for autonom ous therapeutic and diagnostic devices are of our interest, because they m ay one 
day function as silicon-free expert system s. D NA-based logic gates are intended to perform  
as traditional binary logic gates, which turn l's and O 's of input into l’s and O 's of output, 
which form  the central processing units in digital com puters. Recently, Seem an and 
colleagues at New York University have found a clever new way to tease D NA strands into 
m im icking exclusive O R (XO R) logic gates (1 1 7). In the case of an XO R gate, the rule is 
sim ple: when the sam e two digits enter the gate, a 0 com es out; two different entering digits 
return a 1 . In this latest case of D NA com puting, inputs are replaced by single-stranded 
m olecules, and how they bind with each other-base pair to base pair--dictates the 
operations. In essence, the collection of input m olecules that are used set up the problem ; 
once that's done, the answer self-assem bles in a single step. T he near term  goal is to build 
D NA-based com puting m odules and to develop nanoscopic m achines that could exist in living 
organism s, sensing conditions and m aking decisions based on what they sense, then 
responding with actions such as releasing m edicine or killing specific cells.
Logic Operation by Deoxyribozymes
T his biocom puting approach is based on two libraries of nucleic acids, one consisting of an 
allosterically m odified deoxyribozym e (nucleic acid catalysts m ade of D NA) and the second, 
its substrates. A D NAzym e is associated with gene replication only, and they exist only in the 
laboratory. Nevertheless, they are very powerful tools for building D NA-based nanosystem s. 
T he functions of these m olecular units are essential for m olecular logic gates and the 
seam less integration into D NA-based com puting devices. T hese constructs are capable of 
carrying out sim ple arithm etic operations (1 18 ) and have the capability to arrange several 
gates around a com m on substrate. (1 1 9)
T hese devices have oligonucleotides (short ssD NA) as both inputs and outputs. 
Phosphodieseterase deoxyribozym es cleave other oligonucleotides, producing shorter strands 
as outputs. For exam ple, operation of the sim plest sensors is illustrated in Figure 20. T he 
stem -loop of YESx m olecule inhibits the catalytic m odule through the overlap of the stem  
with the substrate recognition region. Hybridization of ix to the com plem entary loop opens 
the stem  to allow substrate binding to proceed. T he YESx gate behaves as a two-state switch, 
with the active state in the presence of input. T he com bination of these sensors for input to 
gate logic is illustrated in Figure 21. Generalized approaches have three-input gates 
(including NO T , AND , AND NO T , AND AND NO T  gates) based on the deoxyribozym e logic. (1 21 ) 
T hese gates are generic and m odular, in the sense that other deoxyribozym es could be
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com bined in parallel into sim ilar constructs, with the expectation of sim ilar behavior. T hat 
m eans, in principle, we can construct enzym atic networks that perform  B oolean calculations 
of any com plexity. At this m om ent, serial connections are prohibitively slow to be used in 
practical devices, thus reported circuits are lim ited to im plicit O R connectivity between 
individual elem ents.
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O UT PUT  E N ZY M E
A DN A enzyme called a de 
oxy ribozyme (fop) consists of 
single-stranded O N A folded 
into a 'core' structure with 
arms at each end that can 
bind to a substrate DN A 
strand that has the comple­
mentary sequences of bases 
separated by a specific se­
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at one end of the substrate 
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quencher molecule M ods 
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To perform  as logic gates analogous to silicon ones, a technology m ust produce specific 
outputs tn response to a variety of inputs. DN A enzym es and recognition m odules 
provide these output and input functions for a system  based on DN A in solution.
Fluorescent 
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IN PUT  SE N SO R
In a DN A structure called a stem-loop, the DN A folds onto itself and zips together to form 
a double-stranded stem with a single-stranded loop (left). W hen a matching input strand 
binds to the loop, it pries the stem apart (ngM
< Input ^[dF-W j^H
' «^s* ^ A A A iM
SE N SO R G AT E
A stem-loop attached to the arm of an enzyme blocks the enzyme's function (7) until an input DN A 
strand opens the controller and exposes the arm UK enabling the enzyme to bind and cleave sub­
strates (J ). T his structure Is also called a Y E S gate because it signals. 'Y es, the input is present*
Input
Figure 20. Functional design of a DNA based logic gate.
37
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DEO XYRIBO ZYM E


UNCLASSIFIED//T O R CIFHCIAL USE  O N LY
Com bining DN A enzym es w ith stem -hop controllers yields a variety of fundam ental 
logic gates that use short strands of DN A as both inputs and outputs. The dealing 
action of the enzym e produces the strands that serve as the gate's output of 1. N o 
cleaving is an output of 0.
AN D G ATE
A logical AN D gate has two inputs and produces an output of 1 only if both inputs are 1 A deoxy - 
ribozyme with a stem-loop on each of its arms acts as an AN D gate. T he dosed stems disable the 
enzyme (/eft), and only when both loops' matching input strands are added can the enzyme 
cleave substrates (mrddfe) T ruth table {rigM  summarizes the gate's function.
AN D -AND -N O T G ATE
A stem-hop controller on the ’back' of a deoxynbozyme acts as a N O T 
input that inhibits the enzyme when the matching input strand is pres­
ent if the stem-loop's input strand is not present (0 ), the stem remains 
dosed and the enzyme cleaves substrates to produce output strands, 
provided that the enzyme's arms are tree (/eft), W hen the input strand 
binds to the controller, the stem opens, deforming the enzyme core and 
rendering it inactive (mddte). A deoxyribozyme with controllers on 
both arms and its back thus behaves as an AN D-AN D N O T  gate. T he 
enzyme is active, cleaving substrates and thus producing the 1 output, 
only if inputs X (M m) AN D Y  (purple) AN D N O T  Z (y^tow) are present
Figure 21. Simplistic rendering of a DNA logic gate.
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Deoxyribozyme-based Boolean Automata
T he deoxyribozym e logic gates were applied to the construction of the first D NA-based 
B oolean autom ata capable of autonom ously responding to hum an inputs: "MAYAs" are 
autom ata playing a gam e of tic-tac-toe against a hum an player. In tic-tac-toe there are a 
m axim um  of 4 m oves by the hum an player when MAYA has the first m ove. T he initial MAYA 
autom aton played a sim plified gam e, always claim ing the center first, and the first hum an 
m ove is sym m etry-restricted to one corner or one side m ove. T hese sim plifications led to a 
representation of the gam e as a series of B oolean form ulae that com pute the autom aton's 
output in each well, based on the hum an inputs present in all wells. T hese form ulae were 
m apped to 23 deoxyribozym e-based logic gates by arranging gates in the individual wells 
around a com m on substrate. T hese "hard-wired" autom ata give the hum an no chance to win 
(Figure 22, Figure 23). (1 20, 1 22) O ne, two and three input deoxyribozym e-based logic 
gates are allosterically m odulated by 32 hum an-operated input oligonucleotides: 9 7 logic 
gates distributed across 9 wells which calculate autom aton m oves, and 32 gates (boxed) 
display hum an m oves by im plem entation of a two-color fluorogenic output system . Even 
though this m echanism  is sim plistic in nature, it has perform ed flawless B oolean calculations.
Figure 22. Basic gate structures, derived from allosterically regulated deoxyribozyme E6, for playing tic-tac- 
toe against a human opponent. The truth tables constructed are sufficient to ensure the human player cannot 
win the game. (120)
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Input strand 4 activates the Y E S 4 gates In 
well 1, which lights up; M AY A has taken 
square 1 tor its second move.
His two inputs activate the 4AN D9 gates 
in well 3; M AY A takes that square.
For his first move, Harry takes square 4. 
He tells M AY A by adding input strand 4 to 
all the wells.
Unfortunately for Harry, his inputs now 
activate the 7-AN D-9-AN D-N O T -1 gate in 
well 2 {he has not added strand 1), and 
M AY A takes that square to win.
T o block M AY A from taking the diagonal, 
Harry takes square 9 by inputting strand 9 
to all the wells.
T he first-generation automaton, M  AY A-I. proves the potential of O N  A logic gates by playing a perfect game of tic-tac-toe. albeit with some 
restrictions to simplify its programming. M AY A plays first, selecting the central square (5), and the human player’s first move must be in either 
the upper left comer (square 1) or the left side (square 4).
M AY AJ 'S ST RUCT URE
T he computer's 3x3 array of wells contains a variety 
of molecular gates in solution, along with substrate 
strands (nof^ow). In wells where any enzymes 
become active, the cleaved substrates fluoresce red. 
T he "gate* in the central well Is a DN A enzyme with 
no stem-loop controllers.
E XAM PLE  G AM E
T he human, “Harry,’ adds magnesium 
ions to all nine wells to switch M AY A on.
T he enzymes in well 5 cleave substrate 
strands, and the well lights up, signaling 
M AY A's opening move (X).
Figure 23. First Generation (MAYA I) DNA-based Logic Circuit that plays tic-tac-toe.
Robotic Bases (The DNA Robot)
Illustrated thus far are various structures that can be built by D NA-based approaches, and 
such com ponents can be com bined into even m ore com plex system s at a nanoscale. As an 
exam ple of the integration of different D NA com ponents, we present here an approach that 
that will eventually lead to the design of D NA "robots." In order to m ake such robots, we 
m ust integrate three, up to now separate, m olecular functions into either the m olecule itself, 
or into the interactions between the m olecule and the environm ent it traverses. T hese three 
functions are sensing, inform ation processing, and m ovem ent. In principle, D NA provides us 
with all these functions, and we should be able to build functional units that could be 
justifiably called m olecular robots solely out of nucleic acids. W e hope that D NA robots will 
enable us to approach on a m olecular scale, the im portant issues in the field of'ordinary' 
robotics such as; evolution, learning, m ulti-robot interaction, self-replications, and self-repair. 
Sensing devices are necessary to extract inform ation from  the environm ent such as 
existence of a specific m olecular species in the solution and shape and properties of the
4 0
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Harry desperately Iries blocking M AY A 
by taking square 7.


UNCLASSI FI ED/ 7T UK UhFiLlAL USE  O N LY
landscapes traversed by m olecules. T he capability for com putation is also needed to analyze 
these data and, in m any applications, som e rudim entary processing units such as the logic 
gate networks shown in the previous section would be enough to achieve useful 
functionalities.
T o exhibit these capabilities, a team  of scientists from  C olum bia University, Arizona State 
University, the University of Michigan, and the C alifornia Institute of T echnology (C altech) 
(1 23) have program m ed an autonom ous m olecular "robot" m ade out of D NA to start, m ove, 
turn, and stop while following a D NA track. T his developm ent could ultim ately lead to 
m olecular system s that m ight one day be used for m edical therapeutic devices and 
m olecular-scale reconfigurable robots— robots m ade of m any sim ple units that can reposition 
or even rebuild them selves to accom plish different tasks. T he researchers constructed a trail 
of m olecular "bread crum bs" on the D NA origam i track by stringing additional single-stranded 
D NA m olecules, or oligonucleotides, off the ends of the staples. T hese represent the cues 
that tell the m olecular robots what to do— start, walk, turn left, turn right, or stop, for 
exam ple— akin to the com m ands given to traditional robots. W e will discuss the "nano 
walker" in greater detail in a later section in this treatise. It is this third function, the 
controlled m ovem ent of m olecules through the aid of nanom otors that will be discussed next.
DNA Nanomotors
Molecular-size m otors have evolved in nature, where they are used in virtually every 
im portant biological process. In contrast, the developm ent of synthetic nanom otors that 
m im ic the function of these am azing natural system s and that could be used in m an-m ade 
nanodevices is in its infancy. B uilding nanoscale m otors is not just an exercise in scaling 
down the design of a m acroworld engine to nanoscale dim ensions. Many factors such as 
friction, heat dissipation and m any other m echanical behaviors are just very different at this 
scale - everything is constantly m oving (under kinetic energy supplied by the heat of the 
surroundings) and being buffeted by other atom s and m olecules (B rownian m otion). T he 
concept of a single D NA m olecule nanom otor was already introduced in early 2002. (1 24 ) 
D NA nanom otors are synthetic biochem ical devices whose m otion can be controlled at the 
m olecular scale.
D NA m olecular m otors will be indispensable parts for the construction of m olecular robots. 
T he m otion of a robot should be well-controlled by m eans of som e m olecular input, or it 
should be driven autonom ously by cues from  the environm ent. First approaches to encode 
m olecular m otion in D NA structures were based on the reversible and input-sensitive 
conform ational changes. For exam ple, the first reported use of a D NA m otor was a 
nanom echanical device which generated twisting m otion along the helix axis based on B -Z 
transition controlled by ionic strength of a solution. (1 25) T hen, the first m olecular tweezers 
were driven by successive reversible branch m igrations of D NA strands, and these strands 
were called "fuel" and "anti-fuel." (1 26) T he next level in com plexity were "rem otely- 
controlled" walkers introduced by Seem an and Pierce, as they were based on a series of 
successive unidirectional conform ational changes driven by strand displacem ent. T hese 
sequential conform ational changes were m icroscopic analogs of m acroscopic com m ands such 
as: "lift the first leg", "drop the first leg to the next available position"; "lift the second leg", 
"drop the second leg to the next available position", with a cum ulative result of a 
translational m ovem ent of a m olecule along a track. O ne drawback of these system s was 
that they were not autonom ous, and that each conform ational change had to be triggered 
separately, while one advantage was that they could have been m onitored easily in bulk with 
fluorescence m easurem ents. T he first autonom ous system s were based on nucleic acid
4 1
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UNCLASSIFIED/ /nW  O rHG T AI UDE  O N  FT
enzym es, e.g., deoxyribozym es, and perform ed either solution phase conform ational 
changes, or were proposed to m ove autonom ously along a linear track over up to four steps. 
(1 27)
A new paper published in the journal N ano Letters details how the researchers created the 
first light-powered nanom otor (Figure 24 ) out of a photoreactive chem ical and a short length 
—  only 31 base pairs —  of D NA. (1 28 ) T he m otor looks a bit like a pair of tweezers. W hen UV  
light hits it, the photoreactive chem ical causes the D NA to bend, which acts as the power 
stroke of the m otor, opening the tweezers. Light in the visible spectrum , in turn, resets the 
chem ical, closing the tweezers. T he team  from  the University of Florida built a new type of 
"m olecular nanom otor" driven only by photons, or particles of light. W hile it is not the first 
photon-driven nanom otor, the alm ost infinitesim al device is the first built entirely with a 
single m olecule of D NA, offering a sim plicity that increases its potential for developm ent, 
m anufacture and real-world applications in areas ranging from  m edicine to m anufacturing. 
In the com ing years, nanom otors could becom e a com ponent of m icroscopic devices that 
repair individual cells or fight viruses or bacteria. Although in the conceptual stage, those 
devices, like m uch larger ones, will require a power source to function. B ecause it is m ade of 
D NA, the nanom otor is biocom patible. Unlike traditional energy system s, the nanom otor also 
produces no waste when it converts light energy into m otion.
I A zobenzene I
3 Stem5' Stem L oop
Figure 24. A single molecule DNA-based nanomotor driven by photons. (128)
Nanom otors can be daisy-chained together, so that sm all m ovem ents on the m icroscopic 
scale add up to large m ovem ents at the m acroscopic scale. In biology, m uscle contraction 
and plant m ovem ent both result from  sm all m otors working together to create big changes. 
Scientists are attem pting to m im ic the m any m olecular m otors that have been proven in 
nature. T oday, biology is acting as a blueprint for the developm ent of m any D NA-based 
devices. O ne such biologically based m echanism  is the spider-like-inspired nanowalker.
4 2
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UNCLASSIFIED//TOR UFHUAL UAL UHL I
Figure 25. AFM Scan of walkers as they follow a track pattern places on 
the surface. Each can take up to 50 steps. Visible is the body of each 
walker as they carry cargo (gold atoms) along the designed path. 
Scale bar is 50 nm. (129)
The Nano Walker; a Spider-like Approach
A sim ple cargo carrying robot was dem onstrated by Gu. (1 29 ) Spiders follow a designated 
path placed on a surface, picking up gold atom s as they pass over them . Such a device could 
be used to collect sam ples from  asteroid or planetary surfaces. O n a m assive scale, they 
could collect m ission critical m aterials from  an exploration site.
In a different approach, a nano-scale m olecular proto-robot with a potential for integration 
with com puting and sensing (i.e., into a real m olecular robot), (1 30) was introduced by 
Stojanovic: T his design starts with a consideration of the following situation; a surface 
covered with substrates in a scaffold configuration is exposed to a single deoxyribozym e that 
will bind to its substrate, cleave it, release both products, and then bind again to another 
substrate, repeating the cycle, for as long as there are substrates available on the scaffold. 
(Figure 26) T his deoxyribozym e would m ove over the surface with the process called self­
repelling random  walk, being attracted m ore by substrates, than by the residual product on 
the surface. B ut every loss of the contact with surface could lead to the rem oval of the 
deoxyribozym e in the bulk solution, with experim entally determ ined processivity (cleaving 
substrates without leaving into bulk solution) into single digits. However, com bining the 
concepts of self-repelling walk of deoxyribozym es and m ultivalency, led to testing 
assem blies with 2-6 deoxyribozym e legs displayed on inert bodies (i.e., spiders), and the 
processivity was increased to up to several thousands. Essentially, the cum ulative binding of 
m ultiple catalysts to substrates would attach the spider tightly to the m atrix, whereas 
individual catalysts would still be able to rapidly cleave substrates, release products, and 
bind new substrates through the process of dissociation and rebinding. If density of
4 3
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substrates and size of legs are adjusted well, the assem bly is continuously m oving to new 
substrate-covered areas. D ue to residual binding of deoxyribozym es to products, even if the 
spiders were surrounded by the product-covered areas, they would be able to m ove over 
them  by ordinary random  walk, until they would find substrates again. Im portantly, 
directional m ovem ent of spiders can be accom plished by aligning substrates in directional 
paths, for exam ple, by displaying them  on self-assem bled structures, including origam i 
(Figure 27). Further, sim ple com puting can be introduced by logic gates as legs. T he nano 
walker could be hybridized to repair D NA based m achinery, including D NA com puters, when 
they are being assem bled, or when they are dam aged from  cosm ic rays, for exam ple.
Figure 26. The Nano walker made at Columbia University is a 
protein molecule decorated with three legs—single-stranded 
DNAzymes, synthetic DNA molecules that act as enzymes and 
catalyze a reaction.
4 4
UNCLASSiFiED/ /nnn G mciT Ai use one t


UNCLASSIFIED// FO R O mtlAL USE  UI VET
Figure 27. Deoxyribozyme-based molecular walker and origami prescriptive landscape, a, The 
NICK3.4A311 spider consists of a streptavidin core, with a 20-base single-stranded DNA (green) 
that positions the spider at the start, and three deoxyribozyme legs, b, The 8-17 deoxyribozyme 
cleaves its substrate at an RNA base, creating two shorter products (respectively 7 and 11 bases in 
length). Dissociation from these products allows legs to associate with the next substrate, c, Spider 
actions: after release by a 27-base single-stranded DNA trigger, the spider follows the substrate at 
a STOP position, d. Schematic of the DNA origami landscape with positions A-E labelled; track 
EABD is shown with I indicating a topographical imaging marker, e, A representative origami 
landscape showing the START position (green), the substrate track (brown), STOP and CONTROL 
sites (red), and a topographical imaging marker (blue). rA, ribonucleotide position at which 
cleavage occurs; dA, deoxyribonucleotide within non-chimeric and non-cleavable analogue of 
substrate at a STOP position. (123)
DISCUSSION
T he first operating quantum  com puters capable of solving real-world problem s will 
com m ence within 1 0 years and be based on ion-trap technology. T his is entirely based on the 
am ount of research resources dedicated to the problem  and the fact that there appear to 
only be engineering challenges rem aining. Atom ic and ion traps require very substantial 
cryogenic and EM shielding system s and are not practical for space travel.
Pure photonic technologies available today have difficulty with both m iniaturization and 
scalability. However, the am ount of active work in the field m akes a disruptive advance likely 
in the 1 0-year tim efram e. O ptical com puters will likely be realized in the 20-year horizon; 
however, the very powerful prom ise of quantum  com puting will still have issues with photon 
loss in any solid state device. T he 4 0-year horizon will see photon technologies play an 
essential but supporting role in distributed quantum  com puting. T he realized system s will 
have radiation tolerance advantages over current sem iconductor technology and are likely to 
augm ent or even replace general purpose com puting devices for space travel.
Hybrid designs utilizing arrays of quantum  dots and photon com m unication channels will be 
an option for space travel supercom puting on the 4 0-year tim escale. T hese system s operate 
at attainable tem peratures without cryonics, and require no m ore shielding than hum ans. It 
is likely that spintronics will be an essential ingredient.
4 5
UNCLASSIFIED//.EQB^KHCMMee-efteT


UNCLASSIFIED/ /FUH UPF1L1AL USE  UN LI
Sim ple organic com puting based on D NA tiles will be realized in the next 20 years. O n the 
4 0-year tim e horizon, useful D NA-based devices will be essential space exploration tools. 
T hese could take the form  of orbital-delivered wireless sensors searching planetary/asteroid 
features or for essential com pounds such as high concentrations of water. D NA com puters 
will be realized on the 4 0-year tim eline. T heir advantage over solid state devices will be the 
ability to repair nanoscale elem ents dam aged in norm al use or by cosm ic radiation. T hese 
will not be the fastest system s in the astro-arsenal, but they m ay be the m ost robust.
CONCLUSION
W e have presented an introduction to quantum  com puting and the technologies that 
com prise the current state-of-the-art. In the 1 0-20 year horizon, we will see optical and 
D NA-based com puters realized on sm all production scales, but their readiness level for space 
travel will be lacking. O n the 4 0-year horizon four m ajor advances in space-ready technology 
will be seen: devices developed for optical com puting will allow an all-optical com puter to 
augm ent or replace general purpose com puters; optical com m unication will play an essential 
role in hybrid designs of space-based quantum  com puters along with quantum  dots; D NA 
devices will perform  sim ple distributed sensor data analyses; and fault tolerant D NA 
com puters will be available for m ission-critical analysis tasks.
4 6
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UNCLASSIFIED// FO R O FFICIAL UDE  O N  Hl*
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