18 july, 2007 metal nanowires that detect molecules reg penner institute for surface and interface...

18 July, 2007

Metal Nanowires that Detect Molecules

Reg Penner

Institute For Surface and Interface Science (ISIS) and the Department of ChemistryUniversity of California, Irvine

Metal Nanowires that Detect Molecules

Reg Penner

Institute For Surface and Interface Science (ISIS) and the Department of ChemistryUniversity of California, Irvine

http://compliance.vpr.okstate.edu/ibc/Forms/Appendix%20D.doc.an objective: fast, selective testing for botulinum toxin in milk...

How botulinum toxin kills:It catalytically cleaves the SNARE proteins required for vesicle fusion leading toacetylcholine release.

Botulinum Toxin as a Biological WeaponMedical and Public Health Management

Stephen S. Arnon, MD; Robert Schechter, MD; Thomas V. Inglesby, MD; Donald A. Henderson, MD, MPH; John G. Bartlett, MD; Michael S. Ascher, MD; Edward Eitzen, MD, MPH; Anne D. Fine, MD; Jerome Hauer, MPH; Marcelle Layton, MD; Scott Lillibridge, MD; Michael T. Osterholm, PhD, MPH; Tara O'Toole, MD, MPH; Gerald Parker, PhD, DVM; Trish M. Perl, MD, MSc; Philip K. Russell, MD; David L. Swerdlow, MD; Kevin Tonat, PhD, MPH; for the Working Group on Civilian Biodefense

Vol. 285 No. 8, February 28, 2001

“As paralysis extends beyond bulbar musculature, loss of head control, hypotonia, and generalized weakness become prominent. Dysphagia and loss of the protective gag reflex may require intubation and, usually, mechanical ventilation. Deep tendon reflexes may be present initially but diminish or disappear in the ensuing days, and constipation may occur. In untreated

persons, death results from airway obstruction (pharyngeal and upper airway muscle paralysis) and inadequate tidal volume (diaphragmatic and accessory respiratory muscle paralysis).”

Vol. 285 No. 8, February 28, 2001

Botulinum Toxin as a Biological WeaponMedical and Public Health Management

Stephen S. Arnon, MD; Robert Schechter, MD; Thomas V. Inglesby, MD; Donald A. Henderson, MD, MPH; John G. Bartlett, MD; Michael S. Ascher, MD; Edward Eitzen, MD, MPH; Anne D. Fine, MD; Jerome Hauer, MPH; Marcelle Layton, MD; Scott Lillibridge, MD; Michael T. Osterholm, PhD, MPH; Tara O'Toole, MD, MPH; Gerald Parker, PhD, DVM; Trish M. Perl, MD, MSc; Philip K. Russell, MD; David L. Swerdlow, MD; Kevin Tonat, PhD, MPH; for the Working Group on Civilian Biodefense

an objective: fast, selective testing for botulinum toxin in milk...

an objective: fast, selective testing for botulinum toxin in milk...

what we’re trying to achieve...

Properties of this device:

● One metal nanowire...● ...that electrically transduces the presence of molecules based on charge, dielectric constant, etc.● ...that recognizes and binds

one particular molecule,ANY molecule.

...this puzzle has three pieces...

2. one metal nanowire

1. electrical transduction

3. recognize and bind.

2. one metal

nanowire(unable to sense anything)...

3. selectivity forone particular molecule

(but not at a nanowire)...

how can we impart “molecular sensitivity”

to metal nanowires?

1. electrical transduction

In 1938, Fuchs* demonstrated that the resistance of very thin (l < 50 nm) metal films increases when molecules chemisorb at the surface of the film.

*K. Fuchs, Proc. Cambridge Philos. Soc. 34 (1938) 100.

Metal nanowires should be poor sensors of molecules,just look at metal nano-films...

References:

“In-plane resistivity of ultrathin gold films: A high sensitivity, Molecularly differentiated probe of mercaptan chemisorption at the liquid- metal interface” Y. Zhang, R.H. Terrill, P.W. Bohn J. Am. Chem. Soc. 120 (1998) 9969.“Chemisorption ande chemical reaction effects on the resistivity of ultrathin fold films at the liquid-solid interface”, Y. Zhang, R.H. Terrill, P.W. Bohn Anal. Chem. 71 (1999) 119.“Effect of molecular adsorption at the liquid-metal interface on electronic conductivity: the role of surface morphology”, G.A. Fried, Y. Zhang, P.W. Bohn, Thin Sol. Films 401 (2001) 171.“Surface roughness of metallic films probed by resistivity measurements”, A.L. Cabrera, E. Garrido-Molina, J. Espinosa-Ganga, I.K. Schuller, D. Lederman, Langmuir 14 (1998) 3249.“Resistance changes of cobalt and niobium films when exposed to hydrogen and carbon monoxide” A.L. Cabrera, W. Carrido-Molina, J. Colina, D. Lederman, I.K. Schuller, Phys. Rev. B 55 (1997) 13999.“Adsorbate-Induced changes in the infrared reflectance and resistivity of metals” K.C. Lin, R.G. Tobin, P. Dumas, C.J. Hirschmugl, G.P. Williams, Phys. Rev. B 48 (1993) 2791.“Multiple mechanisms for adsorbate-induced resistivity: Oxygen and formate on Cu(100)” E.T. Krastev, D.E. Kuhl, R.G. Tobin, Surf. Sci. Lett. 387 (1997) L1051.“Electron density changes and the surface resistivity of thin metal films: Oxygen on Cu(100)”, E.F. McCullen, C-L Hsu, R.G. Tobin, Surf. Sci 481 (2001) 198.“Mechanisms of Adsorbate-Induced Surface resistivity – experimental and theoretical developments”, R.G. Tobin, Surf. Sci 502 (2002) 374.

ref. film adsorbate ΔR/Ro, %

Fuchs et al. poly Au many < 2 %

Tobin et al. Cu(100) O2 and formate 1 - 4 %

Cabrera et al. poly Co & Nb CO and H2 < 0.98 %

Bohn et al. poly Au thiols, amines < 3.5 %

...ΔR/Ro is always positive, always <5%.

But this is not what we observe...Exposure of ≈200 nm dia. silver nanowires to ammonia causes

a prompt, reversible, resistance increase of between 0.1% and 50,000%...

NH3

background: N

2 pulse duration: 5s

7% NH3

Murray, et al. NanoLett, 4 (2004) 665.Murray, et. al., Analyt. Chem., 77 (2005) 5205.

∆R/Ro =80%

...in silver wires, CRIBs are Ag2O

point contacts interposed between particles.

If this is not boundary scattering, what is it? ...the Chemically Responsive Interparticle Boundary (CRIB) model...

...”Bad” sensors exhibit a metallic T-dependence; “Good” sensors exhibit thermally activated conduction...

€

R∝RoαT−To( )For a metal:

For a semiconductor:

€

R∝expΔEkT ⎛ ⎝ ⎜

⎞ ⎠ ⎟

bulk Ag = 3.74 x 10-3

35 measurements

Silver wires should not exhibit photoconductivity...

...photoconductivity in silver wires? We often observe this for wires capable of detecting ammonia..

ΔR/R

o=13%

ΔR/R

o=1.3%

...protonation of surface hydroxyls should minimize surface charge,

yielding negative ΔR/Ro.

Experimental evidence for CRIBs?

1. The physics of conduction in “good” and “bad” ammonia sensors

is very different:● Single nanowire studies using conductive tip AFM...● T-dependence in “good” sensors is activated,

in “bad” sensors it is metallic...● Photoconductivity? Yes!...(Murray et. al. Analytical Chemistry 77 (2005) 5205

Zubritsky, Analytical Chemistry 78 (2006) 2890).

2. Nanowires of pure Ag2O behave identically to “good” silver nanowires sensors...(Murray et. al. Chemistry of Materials 17 (2005) 6611).

3. “Bad” sensors can be made into “good” sensors by electrooxidation.

(Murray et. al. Nano Letters 4 (2004) 665).

2. one metal nanowire

3. selectivity forone particular molecule

(but not at a nanowire)...

✔ Based on these results, it is reasonable to expect

oxidized noble

metal nanowires to electrically transduce the

presence of

charged molecules.

✔ ...because of embedded oxide contacts (CRIBs)...

✔ ...that can be synthesized electrochemically within these

nanowires.

References:Zubritsky Analytical Chemistry 78 (2006) 2890.

Murray et. al. Analytical Chemistry 77 (2005) 5205.

Murray et. al. Chemistry of Materials 17 (2005) 6611.

Murray et. al. Nano Letters 4 (2004) 665.

1. electrical transduction

2. one metal nanowire

3. selectivity forone particular molecule

(but not at a nanowire)...

now, how can one metal nanowire be synthesized,

with control of wire position and size?

1. electrical transduction

glass

Au nanowires

electrodeposited gold nanowires...on glass?

electrodeposited gold nanowires...on glass?

Lithographically Patterned Nanowire Electrodeposition

“LPNE”

Menke et al. Nature Materials, 5 (2006) 914.

...nanowire width and height are controlled independently,

and without cross-talk.

...presently, the smallest nanowires that can be prepared by LPNE are 15-20 nm (w) x 6 nm (h).

Au

noble metal nanowires prepared by LPNE are mechanically continuous, and quite rugged.

...by repeating the LPNE process twice, electrically continuous nanowires can be overlaid in patterns on a surface.

Au Au

Au Au

Pd nanowire

now we’ve got something that LOOKS approximately right...

2. one metal nanowire

3. selectivity forone particular molecule

(but not at a nanowire)...

✔ LPNE = Lithographically Patterned Nanowire

Electrodeposition.

✔ Photolithographic control of wire position, length,

contour.

✔ Fully parallel.

✔ Independent control of nanowire width and thickness.

✔ NOTE: most of these data were generated in a chemistry

laboratory,

using a handheld UV lamp and contact masks.

2. one metal

nanowire(unable to sense anything)...

1. sensitivity to molecules

(with many nanowires and little selectivity)...

how can we engineer a metal surface capable of

recognizing and binding a particular molecule,

ANY molecule?

our collaborator: Prof. Greg Weiss, UCI Chemistry

3. recognize and bind.

wait, isn’t this a solved problem? What’s wrong with antibodies?

Three objectives: 1. Covalently attach virus to a gold surface...2. ...using surface chemistry that rejects nonspecific

binding.3. Electrically detect this recognition and binding.

Full disclosure: NO NANOWIRES HERE.

Our Chemical Recognition Element: M13

Penner and Weiss, Analytical Chemistry, 2007

...from a library of 1011 adhesive “flavors”, we select members that strongly and selectively stick to our

target molecule, “T”...

what’s “T”? Today, in the Greg Weiss lab at UCI: Biodefense proteins

anthrax lethal factorvaccinia (smallpox vaccine) proteins Francisella tularemia (highly infectious

agent) proteins Cholera toxinbotulinum toxin (toxin, in progress)SARS S protein

Human proteinshuman growth factor (drug of abuse)CD4, p56lck, actin, and Fyn (cell

signaling proteins)prostate specific membrane antigen

(prostate cancer marker)

OthersDNA by engrailed homeodomain

displayed on phageEF-Tu (bacterial marker)BSAvarious antibodies

how are viruses attached to the gold surface?

Yang et al. Analytical Chemistry 78 (2006) 3265.

The resulting phage layer is dense, and completely

passivating of the gold surface ...

attached viruses retain the abilityto recognize and binding their target molecules...

PSMA = Prostate Specific Membrane Antigen.

Yang et al. Analytical Chemistry 78 (2006) 3265.

20 nM

linear mass loading and release of p-Ab from covalent virus surfaceas monitored by QCM (LOD ≈ 20 nM).

Yang et al. (2007).

where, in terms of frequency and phase, can we detectthe virus electrode response?

where, in terms of frequency and phase, can we detectthe virus electrode response?

sensitivity is marginally better at 100 kHz.LOD for p-Ab is ≈26 nM.NOTE: Each data point here is a different

electrode!

LOD = 26 nM

[p-Ab], µg ml-1 [p-Ab], µg ml-1 [p-Ab], µg ml-1

wash 1: 0.5 M HCl wash 2: 0.5 M HCl1 x 1 µm AFM images...

why does electrochemical transduction fail after two HCl washes?A working hypothesis: Phage bundling coupled with monolayer desorption.

electrochemical transductionworks here...

...but fails here.

...in spite of the fact that QCM still works.

2. one metal

nanowire(unable to sense anything)...

1. sensitivity to molecules

(with many nanowires and little selectivity)...

✔ Viruses, engineered by Phage Display, can recognize and

bind molecules at

metal surfaces.

✔ ...permitting a modular sensor design...

✔ ...tailorable to ANY target molecule, in principle.

✔ ...rugged (...surviving, right now, 6 hours in high ionic strength

buffers...)

✔ ...electrically detectible...References:

Yang et al. Analytical Chemistry 78 (2006) 3265.

3. recognize and bind.

remaining objective: Put these pieces together.

this is stupid...

20-30 nm

Two problems with this:

1. A 20-30 nm sensing “layer” is doing allthe work.

2. Rsoln is included in sensor signal,requiring recalibration for everysample.

...let’s just measure the conductivity of the membrane,by putting the conductivity cell inside it.

In principle, this accomplishes two things:

1. Increases the electrical path length through the sensing medium (bound phage).

2. Short circuits Rsoln.

photo

resi

st

photo

resi

st

channel

...Phage are electrostatically bound to theAPTES-modified glass channel...

...Phage are electrostatically bound to theAPTES-modified glass channel...

so far: 6 experiments; 6 nanochannel sensors.

40 nm wire height11 mm channel width

50 nM p-Ab150 nM n-Ab

Michael Thompson

Chengxiang XiangNot shown: Erik Menke, Ben MurrayPenner Group, Aug. 2006

QuickTime™ and aGIF decompressorare needed to see this picture.NSF - CHE, DMR, & NIRT

ACS - PRF

Coworkers:

Funding:

Li-Mei Yang