rta eas & pittcon 2010 sers featured talks

Highly Sensitive SER-Active Sol-Gel Substrates

RTA SERS Team: Stuart Farquharson (CEO), Frank Inscore (R&D Director), Atanu Sengupta &

Chetan Shende (Senior Research Chemists)

www.rta.biz

• Substrates• Applications

• Chemical Agents in Water• Pesticides/Adulterants in Food• Illicit Drugs in Saliva• Proteomics

• Devices

Providing Chemical Information When & Where You Need It

Booth 2825


The SERS Promise (if)

The SERS Delivery (then)

• Extend Raman’s usefulness to a vast number of trace chemical analyses

• Enable Raman Spectroscopy to provide routine sub part per million chemical analysis

But… • Can a SERS-active medium meet the

requirements of an analytical instrument?

Performance Criteria

1. Sensitivity (LOD, LOQ, LMC)2. Linearity3. Selectivity4. Reproducibility5. Shelf-Life6. Usable Media7. Sample Requirements: gas, liq, sol8. Production Costs

Surface-enhanced Raman Spectroscopy

When a molecule is within a plasmon field,

the efficiency of Raman scattering can increase by 1 million times!Sub part-per million detection

becomes possible.

Chemical contribution can provide additional 103

enhancement

Single Molecule Detection: requires 1012 -1014

SERS-Active Media


• Electrochemically Roughened Electrodes• Metal Colloidal Hydrosols• Metal Islands or Nanoparticles on Solid Supports• Metal Coated Surface Structures• Self-Assembled Monolayers (SAMs)

Traditional:

Recent:• Metal-Doped Porous Media• Periodic Apertures in Metals• Metal Shells• Fiber Optic Tips

Electrochemically Roughened Electrodes


Features: 50-250 nm wide, 75-200 nm high

Pentaamine(pyridine)Osmium

Farquharson, et al (Weaver), JACS, 105, 3350 (1983)

Adenine in an Electrolytic Flow CellFarquharson et al, SPIE, 3533, 1998

-1.7Vsce 10 sec

735 cm-1


Electrochemically Roughened Electrodes

Limitation:Identical ORCs do not produce

Identical Surfaces.

Silver and gold colloids in solution


30-50 nm Silver Colloid Aggregates (spermine)

Graham, Smith et al, Anal Chem, 69, 4703 (1997)

10-25 nm Silver ColloidLee & Meisel, J Phys Chem,

86, 3391 (1986)

Vapor Deposition on Glass & Sol-Gels


Gold Film on Sol-GelRuthenium Tris bypyridine

20 nm Silver filmBis Pyridyl Ethene

1 micron

5 microns

Vapor Deposition on Spheres


Silver on polystyrene, silica, titania…

Vo-Dinh, Anal Chem, 56, 1677 (1984); ibid, 87, 59 (1987)

10 microns

CWADosimeter

Vapor Deposition…on nanospheres


200 nm Ag on 390 nm spheres

Glucose on 1-decanethiol coating

Haynes et al (Van Duyne), J Raman Spec, 36, 471 (2005)


Benzenethiol on Truncated Pyramids

Haes & Van DuyneJACS, 124, 10596 (2002)

Vapor Deposition Shapes

Metal coated spheres - Nanoshells


Silver on silica spheresJackson & Halas

PNAS, 101, 17930 (2004)

p-mercaptoaniline


200 nm Silver film 150 nm hole

900 nm spacingGhaemi et al. Phys Rev

B, 58, 6779 (1998)

Periodic Apertures

Gold film ~250 nm hole

~450 nm spacingRowlen (web site)

300 nm Gold film On inverted 1

micron pyramidal pits

Perney et al, Optics Express, 14, 847 (2006)

Traditional SERS-Active Media


Major Limitations:

• Electrodes - Irreproducible Roughness• Colloids - Unstable Media (e.g. pH)• Vapor Coated Spheres – no substrate-to-substrate consistency• Specific Structures - less enhancement• Stringent Sample Requirements (e.g. solvent)• Expensive Devices• Irreversible (single measurements)

SERS: silver particles in sol-gel


1 square micron = 12.6 silver particles

Laser spot (325 micron diameter) = 83,000 square microns

i.e. contains 1.04 millionsilver particles

Or the equivalent of 1 perfect hot spot generating 1012

enhancement

10 microns

Which do you want: Sensitivity or Reproducibility?

SERS-Active Substrates


10-3M

10-5M

10-8M(~10 ppb)

benzenethiol

RTA SERS Sampling Systems

Metal Particle

Sol-Gel Matrix

AdsorbedMolecules

Moleculesin Solution

Laser

RamanScattering

2001: Simple SERS Sample Vials

2001

1 10

2004: SERS-Active Capillary


More suited to extract and pre-concentrate

Challenge: specific, fast, sensitive

• Specificity – identify chemical agents & hydrolysis products• No False Positives!

• Speed – monitor poisoned water (batch & continuous)• 10 min or less

• Sensitivity – Requirements to protect • CN – 6 mg/L (6 ppm) • HD - 100 microg/L (100 ppb) TDG• Nerve - 5 microg/L (5 ppb) MPA

Part-per-billion is challenging!


Analysis: CWA Hydrolysis Products

SP

O

O

NSH

NOH

PO

OOH

PO

O

SP

O

OHN

VXH2O + EMPADIASH ethanol

H2O

MPA+

EtOH MPA+ EA2192H2O

+DIASH

PO

O

PO

O

PO

O N

PO

O N

PO

O

PO

O

PO

O

PO

O

PO

O N

C N

F

F

F

GA

GB

GD

GF

OH

OH

OH

HCN

HF

HF

HF

2-propanol

2-pinacolyl

cyclohexanol

MPA

MPA

MPA

IMPA

PMPA

CMPA

H2O

H2O

H2O

+

+

+

+

+

+

+

OH

H2O

H2O

H2O

H2O

H2O ethanol +

OHEDMAPA DMAPA

HCNH2O

H3O+ + CN-

SCl Cl

SOH OH

HDTDGH2O 2 HCl +


SERS: 10 parts-per-billion


MPA

TDG

CN


Parker-Haniffin Intraflow Sample System


Measurements using NeSSI

10 ppb CN-

100 ppb TDG

75 ppb MPA50 ppb

Sunset Yellow

Spiked Water “EWS-2008-002” from Kensico, NY water reservoir


User Interface

Challenge: minimize pesticide contamination


• Need pesticides to meet food demand (US imports 33 million tons of fruit)

• 2.8% of imports exceed guidelines

• Only 1 % is tested

Shende et al SPIE, 5587, ??? (2005)

Challenge: Detect Residues in Food & Feed


Residues in Food Baby Food Feed

DDT carbaryl malathionchlorpyrifos-methyl chlorpyrifos-methyl chlorpyrifos-methylmalathion malathion chlorpyrifos endosulfan permethrin methoxychlordieldrin ethylenethiourea tribufoschlorpyrifos endosulfan pirimiphos-methylchlorpropham chlorpyrifos diazonpermethrin iprodione ethoxyquiniprodione thiabendazole ethionchlordane dimethoate gardona

Requirements 10 ppb to 10 ppm.

Analysis: methyl parathion


Normal Raman

Surface-Enhanced Raman

Normal Raman


Analysis: Chlorpyrifos


Normal Raman


Normal Raman


Swab Test: carbaryl on an apple


1 Spray

4 Measure

2 Swab 3 Extract

Sensitivity: 10 ppb

75 mW of 785 nm1 min



SERS of Melamine

0.5 PPM(X20)

5 PPM

Pure MelamineSimple SERS Sample Vial

Glass Luminescence


SERS of Melamine

0.5 PPM in Solvent(X20)

5 PPM in Solvent

250 PPM extracted from Baby Formula

Simple SERS Sample Vial

Glass Luminescence

Challenge: determine overdose drug


• 1/3rd of all ER cases are drug overdose related• 50% are due to cocaine • Cocaine overdose symptoms are similar to many other ER cases, particularly heart attack

• A 5-min diagnosis would be invaluable to select treatment• Current analysis of drugs use 10-20 ml blood

• Centrifugation to remove red blood cells• Extraction using organic solvents• Separation using chromatography• Detection with UV or Mass Spec• Standards are needed to ensure measurement accuracy• These methods are labor intensive, time consuming,

• Analysis time is typically 30-60 min.

Solution: Saliva analysis by surface-enhanced Raman

• Drug metabolites represented in saliva• Usually 10-50% of blood plasma (1-10 microg/mL)

• Non-invasive (no needles)• Saliva is 99.5% water

• Interfering physiological chemicals 100X less than blood• But Currently analyses require 10-20 cc

• Raman – chemical specificity• SERS – increased sensitivity (goal=1 mg/L, 1ppm)• Simple SERS Syringe

• Small sample volumes – 100 microL (few drops)• Rapid analysis time (1-2 min)

Shende et al SPIE, 6007, ??? (2005)



Analysis: cocaine

300 microliter sample (6 drops)All 0.33 mg/mL

Wavenumbers

Normal Raman

SERS

Drug Detection on a Universal SERS Chip

2 inches


Benzoylecgonine

Methanol

Cocaine

300 microliter sample (6 drops)All ~50 ppm

Simple SERS Sample Vials: Uniform Coatings


Significant improvement in RSD using new high-speed roller

Chemical Residue Detector

5”

10”

3.4”

5 Pounds

A Portable, Field usable SERS Analyzer


Raman Shift, cm-1

TNT

Melamine

Chlorpyrifos-Methyl

Methyl Phosphonic Acid

Aspirin

Aspargine

1-10 ppmChemical Residue Detector

Chemical Residue Detector


Proteomics (Amino Acid Sequencing)

96-Well SERS-Active PlateWe develop SERS Sample

Systems for You

Booth 2825

Challenge: regulate drug dosage


• Chemotherapy drugs also kill non-cancer cells• Dosage is critical • No clinical trials to establish statistical based dosage• Current analysis of drugs and metabolites use 10-20 ml blood

• Centrifugation to remove red blood cells• Extraction using organic solvents• Separation using chromatography• Detection with UV or Mass Spec

• Standards are needed to ensure measurement accuracy• These methods are labor intensive, time consuming, unsafe• Consequently, measurements made on an “as needed” basis

Background: 5-Fluorouracil (5-FU)


• One of most widely used chemotherapy drugs • Colorectal carcinoma

• Structure similar to uracil • Metabolites incorporate into RNA and DNA• Wide genetic-based variation in metabolism, 15-80% inactive• Half life is 5-20 minutes

•Various dosage regimens based on type and phase of cancer

• Concentrations in saliva similar to blood plasma

O

O

F

H

H

H

N

N1

2

34

5

6

Farquharson et al J Raman Spec, 36, 208 (2005), Vib Spec, 38, 29 (2005)

Analysis: 5-Fluorouracil


Normal Raman



Simulated analysis of 5-FU in saliva

ABC

SERS-ActiveLab-on-a-Chip

Sample Injection Syringe

Simple Separation Devices

5FU&

5FUH2

5FdUrd

Leucovorin

A

B

C

600 800 1000 1200 1400 1600 Wavenumbers (cm-1)

Challenge: sensitivity, speed, specificity

• Sensitivity – protect exposed personnel• Anthrax LD50 estimated at ~10,000 spores (100 nanograms)• Goal is closer to 100 spores/cm2

• Speed – need to map area (target 1 min per spot)

• Specificity – extreme minimum in false positives

• Current methods:• DNA or RNA enumeration: (Culture growth - 24 hours) or

Polymerase Chain Reactions (PCR, >4 hours)• test kits (limited shelf life, very high false positive rate)



Approach: measure anthrax signature - CaDPA

Core Wall(proteins-cysteine,

)Ca dipicolinateCortex

(peptidoglycan)

Exosporium

Spore Coat

DNARibosomes

C CO O

O ON

2-

Ca 2+

CaDPA

Farquharson, Maksymiuk & Inscore Appl Spec, 58, 351 (2004)

SERS and RS of dipicolinic acid (DPA)


SERS: 150 mW, 1-min, NR:450 mW, 5-min

10 mg/LSERS

Sat’d KOH sol DPA

by Raman

Extraction & Identification of DPA in 2-min!


1. Added 10 micoliters of SporeDestroyer(1-min digestion)

2. Suck 1 microliter into SER-active capillary (10-sec)

3. Measure SERS of DPA (10% = 220 pg/microliter)

(10-sec placement, 30-sec scan)

0. Dried 2200 spores from 1 microliter

SERS: 220 Spores


100 pg/microL (ppb) reference spectrum

220 pg/microL DPA

1000 pg/microL = 1 ppm, no big deal

Internal Reference

rta eas & pittcon 2010 sers featured talks

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