Optical Sensors and Biomedical Applications

Nilesh J. VasaDepartment of Engineering Design, IIT Madras

njvasa@iitm ac innjvasa@iitm.ac.in

इंजीिनयिरग

िडजाइन

Optical sensorsWhy the interest in optical sensors:High sensitivityS ll iSmall sizeMostly non-invasiveLarge bandwidthLarge bandwidthDistributed / multiplexed sensingRemote sensinggCompatibility with fiber-optic telemetryLow power, weightEt tEtc. etc.

LimitationCost (?)Cost (?)

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Amplitude / intensity based sensors

s,a

I0 I1 I0 e-a l=

l s = Absorption cross sectiona = Absorption coefficientp

= sNN = Number density

Laser

Sample cell

DetectorL

Single pass absorption

Transmittivity = I0 / I1Abosrbance = ln(I / I )Abosrbance = ln(I0 / I1)

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Spectral characteristics of CO2, CH4 and C2H2gases in terms of line intensity based on the HITRAN08 database at 100 kPa and 298 K

Michael E. Webber, Douglas S. Baer, and Ronald K. Hanson, (2001), “Ammonia monitoring near 1.5 m with diode-laser absorptionsensors”, Journal of Applied Optics, Volume 40, pp.31-42. 4

Multi-pass absorption spectroscopy technique for improving detection limit

LaserSample cell d

p g

DetectorMulti pass absorption

RSample cell

Laser

R R

(1 )

d

empty c RDetector

Laser

Intra cavity absorptionMirror Mirror

(1 )

(1 ( ) )

c Rd

c R N dIntra-cavity absorption

SampleR RTransientdigitizer

1 1 1( )

N

c empty

Detector

Laser

p ( ) empty

N = Concentration (number/cm3)L

Cavity-ringdown absorption()= Absorption cross section (cm2)c = speed of light in medium

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VOC Biomarker disease Healthy humans

Acetone ((CH3)2CO)

Diabetes, lung cancer 0.4 – 0.9 ppmBreath analysis using tunable diode laser

((CH3)2CO) Ammonia

(NH3)Kidney disease, asthma 0.3 – 2.9 ppm

Ethane (C2H6) asthma, lipid peroxidation, l d ti

Up to12 ppbLaserDetector

sceloderma, cystic fibrosis vitamin E

deficiency1-Butanol Adenocarcinoma,

Squamous cell> 14.0 ng/l –

30.3 ng/l

Breath sample

Squamous cell carcinoma

30.3 ng/l

3-Hydroxy 2-butanone

Adenocarcinoma, Squamous cell

carcinoma

> 6.2 ng/l –50.3 ng/lComputer

Acetaldehyde Alcoholism, lung cancer Up to 140 ppb

Methane (CH4) colonic fermentation and intestinal problems

3 – 8 ppm

Spectrum

Hexane tuberculosis, liverdisesase

Nitric oxide (NO)

Asthma, NO breath test to

10-50 ppb

Courtsey: Manfred Mürtz (muertz@uni-duesseldorf.de) is with theInstitute for Laser Medicine at the University of Düsseldorf, Germany.His current research topic is high-precision infrared laser spectroscopyand its applications in the life sciences. (NO) test to

monitor inflammation in asthma

Nitrous oxide (N2O)

1-20 ppb

C b O id ti t 1 10Carbon monoxide (CO)

Oxidative stress, respiratory infection,

anaemias

1-10 ppm

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Pulse oxymetry

Oxygen dissociation curveOxygen dissociation curve

Partial pressure of oxygen (kPa)

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Hemoglobin extinction curvesg

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Pulse oxymetry: working principle

HbO2Oxygen saturation = [HbO ] [Hb]2 [ ] [ ]2

ac 660 / dc 660Due to red absorbance

ac 660 / dc 660ac 940 / dc 940

RDue to IR absorbance 9

Phase based measurementsInterferometry techniques and their applications

Michelson Application: Plasma diagnostics, specie identification optical coherent

Interferometry techniques and their applications

specie identification, optical coherent tomography

Mach-Zehnder Specie identification, plasma diagnostics

Application: Gyroscopic measurementsSagnac

pp y p

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Two-beam interference( ) ( )E E E E k t E k t

1 2 01 1 02 2

221 2

cos( ) cos( )1 12 2

total

total total

E E E E kz t E kz t

I E E E

1/ 21 2 1 2 1 2

2 21 2( ) cos( )2

I I I I kz kz

1/ 2max 1 2 1 2

21 2( )2

I I I I I

1/ 2min 1 2 1 2

1 2( )2

I I I I I

max min

max min

Fringe visibility = V =

Wh

I II I

d f l i i liI I IWh

1 2

1 2

en , and perfect polarization alignment1 2 2 cos( )2total

I I I

I I I kz kz

1 2

max min

22 , 0 1

total

I I I V 11

Coherence length

Coherence length: Lc = λ2/(n∆λ ) λ is the central wavelength of the source, s t e ce t a a e e gt o t e sou ce,n is the refractive index of the medium, and ∆λ is the spectral width of the source 12

Optical coherence tomography (OCT)

Coherence length: ∆L = λ2/(n∆λ )

Sample

λ is the central wavelength of the source, n is the refractive index of the medium, and ∆λ is the spectral width of the source

Michelson interferometer

Interferometry uses a series of superimposed electromagnetic waves to gain insights regarding the waves. 13

Diagnostic imaging technique based on back-reflection of low-coherence radiation Non contact, non-invasive Real-time cross-sectional analysis Real time cross sectional analysis Micron resolution in situ

C ti• Continuous sources- Super luminescent/ super fluorescent fibers

center wavelength- center wavelength 800 nm(SLD), 1300 nm(SLD, LED) Power: 1 to 10 mWPower: 1 to 10 mW

- coherence length 10 to 15 μm

• Pulsed lasers- Ti:Al2O3 (800 nm), <3 m resolution

t idth l th ti- tune narrow-width wavelength over entire spectrum 14

Penetration depth and resolutionp

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Timed domain-OCT

• A two-dimensional cross-sectional imaging is acquired by performing successive rapid axial measurements of optical backscattering or back reflection profiles at different transverse positionsreflection profiles at different transverse positions •The result is a two-dimensional data set which represents the backscattering in a cross-sectional plane of the tissue

161. “Optical coherence tomography- principles and applications”, A. F. Fercher, W. Drexler, C. K. Hitzenberger and T.

Lasser, Reports on Progress in Physics, Vol 66, pp. 239-303, 2003.

Frequency domain-OCTFrequency domain OCT• Medical:

– Ophthalmology (flagship of Biomedical OCT)Biomedical OCT)

– Gastroenterology – Dermatology

Endoscopic OCT in intra– Endoscopic OCT in intra-arterial imaging

– Dentistry

• Non-Medical: – Nondestructive evaluation of

highly scattering polymer-highly scattering polymermatrix composites to estimate residual porosity, fibre architecture and structural i t itintegrity

– Nondestructive evaluation of paints and coatingsOptical profilometer– Optical profilometer

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Patient with impaired vision:at e t t pa ed s oThe cause is a macular hole

Patientʼs othe e e isionPatientʼs other eye vision:Impending macular hole, which can be treatedwhich can be treated

http://rleweb.mit.edu/Publications/currents/cur11-2/11-2oct.htm 19

Commercial OCT versus Ultra-high-resolution-OCTresolution OCT

mm

m

W Drexler et al “Ultrahigh resolution ophthalmic optical coherence tomography”W. Drexler et al., Ultrahigh-resolution ophthalmic optical coherence tomography , Nature Medicine 7, 502-507 (2001)

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INTRODUCTION

Application of OCT: Dental cariesINTRODUCTION

• Dental caries – most prevalent oral disease• The mineral equilibrium of the tooth affected• Early diagnosis helps in arresting caries• Early diagnosis helps in arresting caries

progression and non-invasive reversal of caries

DENTAL CARIES• Enamel outermost layer of tooth• Dietary habits change the pH around enamel

E l i b f– Early caries - subsurface mineral loss

– Secondary caries –voids/gaps below cavity g p yrestoration

Micro leakageSecondary cariesEarly caries

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Dental caries: Imaging

B-scans recorded up to a depth of 2 mm indepth of 2 mm in extracted tooth samples

Dark spots seen at a depth of 105 μm from the surface of the toothsurface of the tooth

Unfilled resin filling22

Artificial demineralisation, 840 nm OCT images of tooth surfaces

Before demineralisation

after artificial demineralisation with pH 4.8 for

12 h

24 h

36 h36 h

48 h

60 h

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Dental Restoration: ImagingRestofill composite filling imaged with 1310 nm OCT with two different fillingRestofill composite filling imaged with 1310 nm OCT with two different filling procedures

(a) etch, bond and fill

(b) bond and fill

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Swept-Source OCT:

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Differential absorption based OCT

ScatteringScattering

( ) ( )ln ln ln I Ir ON o ONS d S d dOCT ON OCT OFF a s

ln , ln , ln( ) ( )

S d S d dOCT ON OCT OFF a sI Ir OFF o OFF

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Elemental analysis of species using laser induced breakdown spectroscopy techniquebreakdown spectroscopy technique

[1] pulsed laser beam is focused onto the surface

[2] Radiation

[3] the material starts to evaporate

[2] Radiation energy is locally coupled into the material

[4] Within this material vapor and the surrounding gas atmosphere a plasma is p pgenerated

H: Region of energy deposition P: Plasma

[7] Crater is formed[5] leading to the excitation of the material constituents and

E: element specific emission[6] their spontaneous emission of radiation. [7] The plasma decays and emits element specific radiation

Ref: Reinhard Noll, Laser-Induced Breakdown Spectroscopy: Fundamentals and Applications, Chapter 2, pg-8, c Springer-Verlag Berlin Heidelberg 2012 27

emits element-specific radiation

Plasma Emission Spectra in LIBS

continuous spectrum caused by free-free transition

Plasma cooled down and intensity of Emission lineyincreases

Decay of plasma temperature and intensity ofemission lines

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FeaturesThe following features set the LIBS apart from the pre-existing methods for evaluation:•Non-destructive Nature

– Essentially, non-destructive (20-200 ng ablation)•Independent of material properties•Entirely an optical technique only a visual access of the sample is required•Entirely an optical technique, only a visual access of the sample is required

– Non-invasive•No need to prepare the sample for analysis

The following features set the LIBS apart from the pre-existing methods for evaluation:•Analysis of Alloy and Metallurgical Applications•Environmental Applications•Archaeology and Art•Archaeology and Art•Pharmaceutical Applications•Forensics

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Laser Induced Breakdown Spectroscopy StudiesStudies

Experimental Setup- Laser induced breakdownt (LIBS) bi d ith t l dspectroscopy (LIBS) combined with temporal and

spatial measurements.

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ApplicationsApplications• In Archaeology and Cultural Heritage

– Portability of LIBSNeed not be in contact with sample for analysing– Need not be in contact with sample for analysing

• In Biomedical applications– Composition of tissuesp– To detect excess or deficiency of minerals in tissue,

teeth, nails, or bonesI i d i• In industries– Metallurgical

• Alloy composition• Alloy composition– Radiology– Geological and extraterrestrial Samplesg p

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Forensic analysisLIBS when used in conjunction with refractive index (RI),provided high (>90%) discriminating power for several

l t i l di b l t bilglass types, including beverage glass, automobileheadlamp glass, and float glass from automobile side andrear windows LIBS and RI exhibited a lower discriminatingrear windows. LIBS and RI exhibited a lower discriminatingpower for automobile side-mirror glass, a glass typecommonly found in forensic casework.Single pulse LIBS, used in conjunction with RI, can provide an inexpensive screening for forensic glass samples and may also have utility in other trace analyses.

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• Spontaneous process

Spontaneous Raman Spectroscopy Technique for gas sensing

• Spontaneous process

• Scattered photon into arbitrary direction

• Anti‐stokes lines much weaker

• Weak interaction process (scattering≈ 30 2)10‐30 cm2)

• Two photon process: allows study of molecular vibrations which are not infrared‐active

Advantages:Advantages:• any type of laser source can be employed• the signal of virtually all the species present within the probe volume inside the gas chamber 

can be determined

Disadvantages:• multi‐dimensional measurement is not possible • single‐shot accuracy is relatively low

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Breath analysis using a differential ion mobility sensory g y

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is electric field dependency of ion mobility

and K0 is low field mobility constant. Different ions have different alpha characteristics and ion-mobilities

UV Photo-Ionization lamp (10.6 eV/ Krypton filled/ Heraeus Noblelight PKR-106) with C102RF Excitation system. Volatile organic compound gases with ionization energies less than 10.6eV such as acetone (9.69 eV), ammonia (10.15 eV) and hexane (10.13 eV) are ionized by theUV source.

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(a)

(b)

Differential-IMS Sensor output forDifferential IMS Sensor output for detection of (a) acetone, (b) hexane.

.36

Dual-UV Source Differential Ion Mobility Sensor

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Breath analysis

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Summary1) Intensity / Amplitude based optical sensors

1.1) Absorption spectroscopy based breath analysis) p p py y1.2) Pulse oxymetry

2) Phase based optical sensors) p2.1) Optical coherence tomography

3) UV Photoionization based differential mobility sensor3) UV Photoionization based differential mobility sensor3.1) Detection of volatile organic compounds (VOCs)

Challenges1) Real-time, in-vivo measurements2) Detection of malignant tissues3) Diagnostic and therapeutic applications

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3) Diagnostic and therapeutic applications

LIBS Studies Trace Gas Sensing Pulsed Nd3+:YAG laser base LIBSto determine the elementalcomposition of samples

Current research work is focusedon applications of broadband lightsources such as superluminescentcomposition of samples

irrespective of their states (solid,liquid or gas).Applications: i) Space exploration;

sources such as superluminescentdiode (SLED) in 1.5 m andsupercontinuum light sources in 2m for simultaneous sensing ofpp ) p p ;

ii) Remote LIBS for detecting thecontaminant layer on wind turbineblades; iii) Condition monitoring, such

gmultiple gases.Applications: i) Simultaneousmeasure- ment of NH3 and H2O; ii)

as dissolved Cu in high voltagetransformer oil.

3Bio gas sensing; iii) Particleconcentration measurement

S

Multipass cell

lSuperluminescentDiode (SLED)

Optical spectrumanalyzer

Optical fibercoupling

Acknowledgements• Kyushu University, Japan• Applied Optics Laboratory, IIT Madras, Indiapp p y, ,• Research Scholars of Opto-mechatronics Laboratory

THANK YOUH NK YOU

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Notes: Date: / /

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