Detection and identification how low can you go · 2017. 7. 24. · Animals and insects do this all the time The sense of Olfaction allows animals to detect prey, threats and find

© Crown copyright 2017 Dstl

24 July 2017

Detection and identification –

how low can you go ?

Dr Steve Nicklin

Senior Fellow

Explosives Detection Group

Defence Science and Technology

Laboratory

[email protected]

Content

• Bit about my career

• Bit about Dstl

• Bit about my group

• Bit of chemistry

• Bit of bioiolgy

• Bit about our S & T challenges

• Bit about pushing the boundaries


24 July 2017 • OFFICIAL

My career so far

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BSc in Cellular Pathology and

PhD in Immunology from

University of Bristol

• OFFICIAL


24 July 2017

Post Doc at Wellcome Research

Laboratory. Dept Experimental

Immunobiology, Beckenham, Kent


24 July 2017

British Industrial Biological Research Association Immunoassays/ immunotoxicology



• Defence Science and

Technology Laboratory

– Part of UK Ministry of Defence

• Provides independent,

impartial S&T advice to MOD

and UK government

– Defence and security

– Including deployed operational

support

• Delivers UK defence research

programme

@ 60% delivered through

industry and academia


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Our people

• OFFICIAL


24 July 2017

4,500 people- staff in UK + international

collaboration and secondments across the world


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Core sites


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PORTON DOWN

FORT HALSTEAD

PORTSDOWN WEST ALVERSTOKE

We are split across 9 science and

technology capabilities



We work across government


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Explosives Detection Group (EDG)

• About 70 staff – broad range of disciplines

• Mission – to deliver operationally focussed science and

technology to support and enhance cross-government

explosives detection capability

• Broad customer base – MOD and OGDs


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Explosives Detection

Equipment

Signatures and

Sampling

Canine and Biosystems

Project Management

How we fit together



Signatures and Sampling Team

• Understanding trace and vapour

• Fundamental studies

• Scenario characterisation

• Characterisation of novel threats

• Vapour pressure measurements

• Vapour signature

• Composition

• Development of trace and /vapour

standards

• Explosives contamination studies



Equipment capability



Explosives Detection Equipment Team

• Technology development

• Industry and academia

• Users

• International research collaboration

• Technology assessment

• Value added testing

• Development testing protocols

• Industry engagement

• Support to operations

• Equipment trials

• Training

• Urgent operational requests



Canine and Biosystems Team

• Understand the canine capability to detect

current and future threats by benchmarking

capability

• Provide solutions to fill capability gaps by

developing training aides and methods

• Optimise performance through improved

animal training and welfare

• Meet future requirements by developing

novel biological approaches



Working with industry



Working with academia



Bit of chemistry • Task was to develop a simple to use, hand held test

system capable of the selective and specific identification

of visible quantities of explosives

• Designed to resolve the false alarm issues associated with

Griess based wet chemistry tests



naphthyl-ethylenediamine Sulphanilamide

Target materials


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TNT

PETN RDX

• OFFICIAL


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Why not use antibodies ?

• Highly Specific

• Low FAR

• Sensitive

• Novel Formats

• Safe

• Generic

• OFFICIAL

Copyright 2014 Azo Materials

Approach

• First needed to raise antibodies against explosives

• Problem: Explosives are low molecular weight and far

too small to be immunogenic (haptens)

• Solution: Attach linking groups to the explosives and

couple to a large immunogenic carrier protein



Approach

• First needed to raise antibodies against explosives

• Problem: Explosives are Low molecular weight and

far too small to be immunogenic (haptens )

• Solution: Attach linking groups to the explosives and

couple to a large immunogenic carrier protein



Carrier Protein

TNT hapten synthesis –in house


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Carrier Protein

Carrier Protein

TNT TNBS

• OFFICIAL

PETN hapten synthesis - EMR *


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* Mike Blackburn et al Krebs Institute Sheffield

• OFFICIAL

RDX hapten synthesis - EMR *


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* Mike Blackburn et al Krebs Institute Sheffield

• OFFICIAL

Monoclonal antibody production


Copyright 2008 · Nature Chemical Biology

Immunoassay concept

• Lateral flow competitive inhibition assay

– free analyte blocks binding of colloidal gold bound hapten-

protein conjugate to immobilised anti– explosive antibody




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Worlds first “pregnancy test” for explosives

Without the chemistry this would not have

been possible

• OFFICIAL

But the real the challenge

Is to detect:

• Low molecular weight compounds

• With low- very low volatility

• In the vapour phase in free/moving air

• In real (or near) real time

• In complex and varying backgrounds



Animals and insects do this all the time

The sense of Olfaction allows animals to detect

prey, threats and find mates by detecting

volatiles at vanishingly low levels under the

harshest environmental conditions

Vapour Pressure


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• Whereas some explosives

have vapour pressures

amenable to detection

others have vanishingly

low vapour pressures

– TNT ~ ppb

– RDX, PETN ~ ppt

– HMX ~ppq

Figure © Östmark et al, Propellants Explos. Pyrotech. (2012) 37, 12 – 23

• OFFICIAL

Dogs can provide this capability

Dogs can be trained to:

• detect targets in still air

• trail and follow vapour plumes in moving air

• follow tracks across various terrains

• offer exquisite sensitivity

• but dogs …….




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Olfactory inspired sensing

seeks to exploit elements

from olfaction to develop a

new technology based

approach to detection

• OFFICIAL © Crown copyright 2017 Dstl

24 July 2017

• However In nature OBPs / OR are not high affinity ligands

• OR show affinity for a range of odour molecules and a

single odorant molecule may bind to a number of olfactory

receptors with varying affinities.

• Thus a single odorant can activate a number of different

odorant receptors.

• So in the real world “everything” binds across the

spectrum of receptors

One way forward ?

• OFFICIAL © Crown copyright 2017 Dstl

24 July 2017

• So rather than focussing on high affinity receptor

ligand binding events we are now exploring the use

of arrays that offer binding across a range of different

receptors with a broad range of affinities

• Collect data in a time resolved fashion.

• Train against the “normal” background

• Then use signal processing and anomaly detection

techniques to highlight novel / unexpected binding

events

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HuProt™ - the world's most

comprehensive human protein

arrays

Large protein arrays are now

increasingly available for “drug

discovery”

Advantages of going smaller

• Nanoscale morphology provides a high surface-to-

volume ratio that increases receptor ligand

interactions.

• Low cost, scalable arrays made up of “individual

sensors”

• Low power – compatible with liquid/ vapour phase dtn

• Nanoscale sensors are increasingly reporting

pico- (10-12), femto- (10-15 ) and atto-(10-18) LOD

• Some predict zepto -(10-21) ???


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Emerging nanostructures including:

Nano -particles, -holes, -wires

-tubes. –fibres – mesh and --ribbons

offer a range of platforms for

supporting binding ligands and

interfacing with electro/optical devices

Goldsmith et al Readout of Olfactory Receptor Proteins ACS Nano,

2011, 5 (7), pp 5408–5416

Goldsmith et al have

already coupled

olfactory receptor

membrane proteins

onto carbon

nanotubes

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Copyright © 2011 American Chemical Society

Plasmon Resonance Imaging Using Nano Lycurgus Cup Arrays AOM :1 2013 Gartia et al

Nanoplasmonic array

based sensing using

nanocups exploits

biomolecular recognition

and allows integration

into microfluidics devices

for lab-on-chip-

applications

• OFFICIAL

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Copyright © 2013 Advanced Optical Materials

First report of Peptide Functionalized

Nanoplasmonic Sensor for Explosive Detection

• OFFICIAL

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Single nanocup

Gold Nano

Particle

Anti-TNT Peptide

Zhang .et al Nano-Micro Lett. (2016) 8(1):36–43

Copyright © 2016 N-ML

But are we any closer matching

olfactory performance ?

• OFFICIAL


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Issues still to be resolved

• How do we get real world “vapour” to the sensors ?

• How do we cope with mixed backgrounds ?

• How do we collect/concentrate/deliver odours ?

• How do we avoid poisoning ?

• Can we use orthogonal sensing - parallel arrays ?

• Should we explore Hybrid systems ?

• We also need better

– Real-time “on edge” signal processing/ signal amplification

techniques

– Reliable algorithms/ anomaly detection /library searching


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24 July 2017

Good Ideas are

always welcome

Need funding or advice ? Check out the “Defence and Security Accelerator”

and “The MoD open call for Innovation”

Documents

Detection and identification how low can you go · 2017. 7. 24. · Animals and insects do this all the time The sense of Olfaction allows animals to detect prey, threats and find