Detection of Drugs With Cantilever-Enhanced Photoacoustic Spectroscopy

Dr. Jaakko Lehtinen, Client Partner, Gasera Ltd. Pittcon 2017, 6.3.2017, 09:30 AM

Gasera Ltd. Lemminkäisenkatu 59, 20520 Turku, Finland

Projects overview

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Two projects in FP7 program: CUSTOM and DOGGIES One project in H2020 program: IRON Some work is also done outside these projects

•  Photoacoustic effect was discovered in 1880 by Alexander Graham Bell

•  This theoretical potential has not been reached, since conventional microphones have been used for sensing the pressure pulses

•  Gasera’s novel cantilever sensor technology allows the use of the full potential of the photoacoustic phenomena

Photoacoustic spectroscopy is based on the absorption of light leading to the local warming of the absorbing volume element. The subsequent expansion of the volume element generates a pressure wave proportional to the absorbed energy, which can be detected via a pressure detector.

Photoacoustic spectroscopy

PHOTOACOUSTIC GAS CELL IR SOURCE

MICROPHONE

IR FILTER

CHOPPER

A typical setup of a conventional PAS system

GAS SAMPLE

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Key inventions •  Cantilever sensor

–  Over 100 times greater physical movement can be achieved compared to conventional microphone membrane – cantilever has very low string constant 1 N/m

–  Highly linear response •  Optical readout system

–  Contactless optical measurement based on laser interferometry

–  Measures cantilever displacements smaller than picometer (10-12 m)

–  Extremely wide dynamic measurement range

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Benefits of cantilever enhanced PAS

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•  Absorption is measured directly in PAS which makes the measurement very accurate and free of drift -> stability and reliability, easy to use

•  Cantilever sensor provides high sensitivity –> below ppb detection limits •  Sensitivity is not dependent on the optical path length -> wide linear dynamic range, miniaturization,

low sample volume •  Many different sources can be connected to one cell -> multi-gas capability •  Possibility to heat the sample cell -> suitable to wide range of process applications

CUSTOM-project

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CUSTOM - Drugs And PreCUrsor Sensing By ComplemenTing Low COst Multiple Techniques. The project has started in 2010 and ended in 2013. The aim of the project is to is to build a portable device for drug precursor sensing from vapor phase based on the two orthogonal techniques, which are laser photoacoustic sensor and fluorescence optochip. Development of the cantilever enhanced photoacoustic detector combined with the widely tunable external cavity quantum cascade laser is introduced.

Example measurement with CW EC QCL - setup

•  Example measurements were done with continuous wave external cavity quantum cascade laser (CW EC-QCL ) provided by Daylight Solutions.

•  The wavenumber range was between 1020 cm-1 – 1100 cm-1. •  Example gases that were measured were: BMK and Safrole. •  The power of the laser at this wavenumber range was between 0 mW - 62 mW. •  The photoacoustic cell was Gasera PA201 detector (cell diameter 4 mm, length 100 mm). •  Amplitude modulation with mechanical chopper was done. •  FFT software was used for selecting amplitude from the modulation frequency – (phase lock would give better

results by order of 2)

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Laser

Chopper

Photoacoustic detector

Beam path

Example measurement - BMK and Safrole

•  The measurement was performed by modulating the amplitude mechanically by chopper and tuning the laser wavelength in 0.1 cm-1 steps from 1020 cm-1 to 1100 cm-1.

•  Comparison to FTIR measurement was performed indicating a very good match between the line positions and spectrum details.

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Figure 3. The IR spectra of several drug precursors. Courtesy of CUSTOM project.

The sample of 100 ppm of phenylpropanone (BMK) was measured with a detection limit 2xRMS of 160 ppb (total response time about 60 s).

Figure 4. PAS measurement of BMK and FTIR measurement in comparison.

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The sample of 100 ppm of safrole was determined to have a detection limit of 24 ppb (total response time about 60 s)

Figure 5. PAS measurement of Safrole with FTIR comparison measurement.

Table 6. Sensitivity of PAS with EC-QCL to BMK and Safrole.

BMK (100 ppm) Safrole (100 ppm)

Wavenumber (cm-1) 1084.5 1059.0 Laser power (mW) 7.08 4.01

Signal 0.069 0.538 Noise (2xRMS @ 1 s) 1.13eE-04 1.28E-04

DL (ppm) 0.163 0.024

5.4 Measurement of Acetylene

Acetylene measurements were done with wavelength modulation technique, with a fiber coupled DFB laser. The fiber-coupled laser was a FITEL FRL15950 with center wavelength of 1530.1 nm with output power of 40 mW. The DFB diode laser can be used with small signal modulation i.e. wavelength modulation, thus there is no need for a mechanical chopper. The measurements were done with 100 ppm of acetylene and Ultra High Purity Nitrogen (5.0). The results are presented in the table below.

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• Funded by the European Commission under the FP7-Security programme

•  Project started in 2012, ended in November 2015 • The Consortium of 14 partners from 5 EU countries DOGGIES project aims at demonstrating: • An operational movable stand-alone sensor for an efficient detection of hidden persons, drugs & explosives

• “Orthogonal” trace detection • Mid-Infrared spectroscopy, based on photoacoustic detection (PAS) with widely tunable integrated MIR source i.e. MIRPAS

• Ion Mobility Spectrometry (IMS), with non-radioactive ionization source

• Using specific pre-concentrators and advanced software to provide reliable detection in real environments

DOGGIES = Detection of Olfactory traces by orthoGonal Gas identification technologIES

DOGGIES-project

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Lab testing of the prototypes Headspace measurement of drugs and explosives with MIRPAS and commercially available EC-QCL. Measurements done at INPS, Lyon.

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Lab testing of the prototypes

Multi-gas analysis with EC-QCL PAS Multi-gas analysis for air quality measurements Tuning range: 1000 – 1250 cm-1

Resolution: 1 cm-1

3 minutes response time ppb-level detection limits

(1 – 26 ppb with analysis)

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Photoacoustic spectroscopy

Photoacoustic spectroscopy holds the promise of miniaturization without sacrificing the performance Compact scanning lasers enable multi-gas detection in portable form factor

Measurements with hair samples

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•  A non-invasive drug-testing application •  Drugs enter hair via circulation •  A longer detection window of drugs in hair •  Occasional, random or constant abuse can be detected •  Drugs concentrate to the center of hair

Benefits of photoacoustic spectroscopy: • Measurement does not consume sample material

• No sample preparation needed • Depth profiling

Detection of drugs in hair

•  FTIR-PAS measurement without sample pre-processing

•  Hair samples from cocaine overdose patients were measured (12 samples)

•  Hair samples from a clean reference group were also measured (12 samples)

•  20-30 mg sample material was used per measurement

•  90 s measurement time •  Cocaine content was previously

measured with MS to be between 1,5 and 38 ng/mg in different samples

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Detection of drugs in hair

•  Principal component analysis was used in the spectral analysis

•  Data processing: •  Selection of the wavelength ranges •  Normalization of the spectra by the

area •  Second derivative •  Normalization of the single spectral

points

•  Cocaine users could be separated based on their spectra

Micro-sample studies

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•  Single hair fibers were also investigated •  Smallest measured fiber was only 0.5 mm long •  With single fibers, it is possible to study the time line of drug abuse •  Currently Society of Hair Testing recommends the use of more than 20 mg of hair material for reliable analysis

Solid phase drug measurement •  FTIR-PAS measurement of

different drugs •  Study made in collaboration with

Crime Lab of Finnish Police Forces

•  No sample preparation •  Fast contactless measurement

FTIR-PAS measurement of cannabis

•  Police wants to know the THC-level of the cannabis plant

•  Different parts of the cannabis plant were measured •  Chemometry can be used to define the concentrations

of the different compounds

Miniaturization

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•  FTIR -> scanning EC-QCL •  Photoacoustic spectroscopy can be utilized in field use for solid samples as well