sensors on the move. inoculated sensing automata for the...
TRANSCRIPT
Dario Narducci Dario Narducci
Sensors on the move. Inoculated Sensing Automata for the Early
Detection of Endogenous Diseases
Dario Narducci and Gianfranco Cerofolini,
Dept. Materials Science,
University of Milano Bicocca, Milano (Italy)
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We grow old!
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Life Expectancy at Birth by Epoch
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-10000 -8000 -6000 -4000 -2000 0 2000
20
30
40
50
60
70
80
L
ife
Expe
cta
ncy a
t B
irth
(y)
Year
0.001 y/y
1900 1925 1950 1975 200040
50
60
70
80
0.29 y/y
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Life Expectancy at Birth by Regional Area
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Source: CIA World Factbook 2011
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Life Expectancy at Birth by GOP
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Causes for Death
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Source: WHO
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Immune system is the complex group of defense responses found in humans and other advanced vertebrates that helps repel disease-causing organisms (pathogens).
Immunity from disease is actually conferred by two cooperative defense systems, called nonspecific, innate immunity and specific, acquired immunity.
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The immune system
Source: Encyclopedia Britannica
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Why the immune system fails
• The way the immune system works is driven by evolution.
• In the disposal theory of aging, no investment is made in
soma maintenance exceeding lifespan expectation in the wild
• Homo Sapiens’ lifespan in the wild can be evaluated to range around 30 years
• Therefore, the immune system is not programmed to
effectively detect and terminate age-related diseases (e.g. cancer, Alzheimer disease, Parkinson disease, etc.).
T.B.L Kirkwood, Phil. Trans. R. Soc. Lond. B, 352, 1765 (1997)
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Mission of the artificial immune system
The artificial immune system (AIS) should
• supplement the immune system
• bridge the evolutionary trend to strengthen immune response to age-related illnesses
• not interfere with it
• recognize pathogenic states poorly recognized by the immune system
• eventually terminate pathogenic agents.
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What Is a Sensor (in case you didn’t know)
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• optical or spectroscopic phenomena, including
– fluorescence of specific immobilized molecules that get modified by the interaction with the analyte;
– surface plasmonic resonance (SPR), induced or depressed by adsorption of the analyte onto an eventually functionalized metallic surface;
• electrochemical processes, ranging from Nernst potentials developed by equilibrium concentration cells to limiting current devices;
• electrical response modulation of (wide-gap) semiconductors, such as in conductimetric devices and field-effect transistors;
• adsorbed mass variations, measured by using piezoelectric microbalances.
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Common Sensing Methods
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• Sensitivity: Note that, since in general μ(c) is non-linear
• Selectivity:
• Response times, both upon injection and removal of the analyte;
• Lifetime under operative conditions.
Sensing Figures of Merit
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( )=S cc
= iij
j
Ss j
S
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Signal Handling
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Glomeruli
ORNs
ORs
2nd order neurons
to the cortex
chemical stimulus
to electronics
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1. a sensor based upon nanostructured transduction layers such as nanoribbons, nanobelts, nanowires, nanoparticles, nanotubes, derivatized fullerenes, or quantum dots;
2. a sensor able to detect ultra-traces of a given analyte (ppb or lower), this generally implying sub-micrometric sensing probes
3. a sensor capable of nanometric space-resolved detection.
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Definition(s) of Nanosensor
D. Narducci, Sci. Adv. Mater., 3, 426 (2011)
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• Nanostructuring here primarily provides a simple tool to increase the surface-to-volume ratio, raising the device response
• Typical example is the use of functionalized Ag NPs (> 100 nm) to detect aromatic hydrocarbons by SERS
• This increases the active area enhancing its sensitivity and lowering its detection threshold.
• Aromatic molecules form supramolecular complexes with surface linkers
• Detection threshold can be lowered down to the nanomole range, about three orders of magnitude lower than standard SERS.
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Nanomolar Detection
L. Guerrini et al., Anal. Chem., 81, 1418 (2009)
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Space-Resolved Bionanosensing: An Example
• Probe is a thin (30 nm) fiber tip that was – derivitized using
glycidoxypropyltriethoxysilane (GOPS)
– coated with a 50-100-nm thick Ag layer
– functionalized using 1,1'-carbonyldiimidazole as linker
– activated by incubating it in an antibody solution
• the sensing device mapped benzo[a]pyrene within cells (1-10 μm) by sampling it while laser pulses were sent through the fiber
• Total fluorescence emission was measured
Especially relevant for intracellular monitoring
Word of cautions: measurements can modify cellular equilibria
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T. Vo-Dinh, Nat. Biotechnol., 18, 764 (2000); Spectrochim. Acta, 63, 95 (2008)
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Nanowire Functionalization
Nanowires can be used to build NanoFET, adsorption modulating carrier density
Sensitivity down to the single molecule
They are not quantum devices, instead
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al. et C.M. Lieber, Nanomedicine, 1, 51 (2006)
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CNT Functionalization
Also CNT can be functionalized with affine biosensors
In NanoFETs CNTs are linked onto polymers or metals, not onto Si
They are fully quantum devices
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al. et C. Dekker, Nano Lett., 3, 727 (2003)
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• None of these devices are portable nanosensors according to definition # 2
• NanoFETs are good examples of downscalable systems that could be eventually used as probes of moving sensors
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Outlook
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Swimming Nanosenors
• Nanoprobes have been built enabling detection of metabolites with a size in the 10-nm range
• Technology exists to manufacture information processing devices (processors + memories) smaller than 1 μm, yet powerful enough to collect and process the information provided by the nanosensors
• Micromechanical devices have entered their submicrometric age
Times are mature for micrometric automata to be built, integrating sensing, computing and communicating systems with nanomechanics
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Each automaton should be endowed with the following functions:
• Navigation & motility
• Biomimesis
• Recognition
• Docking capability
• Power supply
• Signalling capabilities
• Some kind of intelligence
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Features of the nanobots
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A vision of the AIS
Inspiring its architecture inspired to the immune system, the auxiliary surveillance system could be formed by
• a central unit, resident in the organism,
• a number of automata swarms, each swarm being specialized to a certain tissue and organ.
At least, automata should:
• Navigate through the (circulatory) system
• Visit cells
• Recognize one or more pathologies
• Report them to central unit
Their efficiency would however increase if they could climb chemical gradients, heading for abnormal cells.
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G.F. Cerofolini et al., Adv. Sci. Lett., 3 (2010) 1
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Programmed vs. Self-Motility
Nanomotors cannot rely upon standard propulsion methods due to the low Reynolds numbers at the nanoscale.
A fully different approach may be based upon rectified Brownian motion, which has been invoked as responsible for a number of biomolecular transport phenomena, from ubiquinone diffusion across cell membranes to allostery, from ATP transport to muscle fiber dynamics.
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R.F. Fox, Phys. Rev. E, 57 (1998) 2177
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Brownian motion is due to thermal noise in a medium:
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Not simply jazzing around
2
( ) 0
( ) 2
v t
v t D
No net displacement is observed when the system is in equilibrium.
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When the system is out of equilibrium, fascinating (and somewhat counterintuitive) phenomena may be observed:
1. In the presence of an asymmetric potential landscape (object), BM can produce a net displacement of nanometric particles
2. Such a displacement may head opposite to a macroscopic, external potential nanoparticles climbing (instead of following) the potential itself
Not simply jazzing around
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D. Narducci and G.F. Cerofolini, in “Nanomedicine in Diagnostics” (2012), in press.
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Walls allowing particles with E > E0 only to travel through
The Feynman Ratchet and Its Descendents
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In this form, the device is just a paradoxical attempt to violate the 2nd law of thermodynamics – quite obviously failing.
But, if we add the second ingredient (being of out of equilibrium) things change.
C Van den Broeck et al., New J. Phys., 7 (2005) 10
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Rectified Brownian Motion
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U
x
U = Uratchetx F
U
x
U = x F
In the absence of asymmetric potentials, the nanoparticle moves downhill. If the external potential is not too large compared to Uratchet and to kBT, then the momentum associated to the thermal noise brings the nanoparticle to the local top of the potential landscape The probability of passing by fluctuation the hill on the right is larger than moving to the left. R.D. Astumian, Science, 276 (1997) 917
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Note that:
• RBM does not violate the 1st law of thermodynamics (q w)
• RBM does not violate the 2nd law of thermodynamics either because Tratchet < Tambient
• RBM does not work against diffusion but because of diffusion
• RBM is impossible at equilibrium, and is mostly effective far away from equilibrium (non-linear region).
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Rectified Brownian Motion
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Chemical Asymmetry as a Motility Engine
grad
ien
t
displacement
Walls should filter particles by energy − but they may also operate by elastically or inelastically reflecting particles based upon their energy. For instance, one might modify two surfaces by grafting with molecules with different affinity toward the species setting up the gradient.
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Nanowires
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G.F. Cerofolini et al., Semicond. Sci. Technol. 25 (2010) 095011
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How many nanowires?
• The approach does not require critical lithography
• Nanotech is at reach by converting vertical spacing into horizontal spacing
The maximum wire density computes to
δmax ≈ R / (tA + tB)
so that δmax ≈ 106 cm-1.
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tA
tB
G.F. Cerofolini et al., Semicond. Sci. Technol. 26 (2011) 045005
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Nanowires are flexible
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M. Ferri et al., Microelectr. Eng., 88, 877 (2011)
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Multifunctionalization
G.F. Cerofolini et al., J. Nanoeng. Nanomanuf., 1, 1 (2011)
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• An artificial immune system is needed to significantly extend human life expectation
• Technology (microelectronic + nanoscience) is mature enough to make nanoautomata a realistic yet ambitious target for R&D
• Nanosensors have shown already capabilities to probe down to the single molecule
• Rectified Brownian Motion opens new yet largely unexplored possibilities to drive automata through the circulatory system
• RBM adds a natural drive to the swimming engine
• NW manufacturing in large amounts sets a suitable hardware platform to implement such an idea
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Summary and some conclusions