FIBER OPTIC RS-OCT PROBE John Acevedo Kelly Thomas Chris Miller Advisors: Dr. Patil Dr. Mahadevan-Jansen

Epithelial cancer types  Epithelium – cells that line hollow organs and make up the outer surface of the body (skin)  Basal Cell Carcinoma:  The basal cells line the deepest layer of the epidermis  1 million new cases are diagnosed each year in the U.S.  Squamous Cell Carcinoma:  Flat, scale-like cells  More than 700,000 new cases are diagnosed every year.  Chronic exposure to sunlight is the cause of most squamous cell carcinoma and basal cell carcinoma.  Optical imaging such as Optical Coherence Tomography (OCT) can noninvasively serve as a diagnostic and monitoring tool of epithelial cancers, and can evaluate therapeutic responses

RS and OCT are complimentary Raman Spectroscopy  Strengths  Biochemical Specificity  Limitations  No spatial Information  Susceptible to sampling error Optical Coherence Tomography  Strengths  Micron-scale structural resolution  Real-time imaging speeds  Limitations  Insensitive to tissue biochemical composition

Procedure 1. Turn on OCT component 2. Acquire tomographical map 3. Detect area of interest 4. Turn off OCT component 5. Turn on RS component 6. Acquire biochemical composition of area of interest 7. Turn off RS component

Dr. Patil’s RS-OCT probe

Reason for fiber optic RS-OCT probe  Improve detection and diagnosis of cancer  Hand held device will facilitate the use RS-OCT probe  A fiber optic probe will decrease the size of the current probe  Potential endoscopic use, non-invasive  Cost effective  Current skin probe~$4000  Our design ~$470  Biopsies ~$150-$1000  Reduce the number of biopsies taken. Over 2 million people diagnosed with epithelial cancer a year ProductPrice Fiber Optics$100 Platinum Alloy coil$50 Focusing Lens$200 Polymer block$100 Electrodes $20 Total$4 70

Problem Statement 5” 8”  Miniaturizing sample arm of current RS-OCT probe

Design Criteria  Meet existing RS-OCT probe performance and functionality  Decrease size of probe to < 1 cm in diameter  Reach a scan rate of RS and OCT to 4 frames per second  Reach a scan range of at least 3 mm depth  OCT sensitivity of -95 dB  RS collection efficiency of 10 seconds  Spot size for OCT should be < 50 microns Determined by depth of focus

RS and OCT existing designs Raman Spectroscopy  Current Probe Design  Direct light source surrounded by 7 detection fibers Optical Coherence Tomography  Current Probe Design  Forward facing  Bundle-based  MEMS mirror Spectrograph CCD 785 nm  m fibers BP filter Notch filters P sample = 80 mW t acq < 5 sec

Challenges  Quality compensation from combining RS and OCT  RS requires narrow band of light source and multi- mode fibers for optimum specificity  OCT requires broad band of light source and single- mode fibers for optimum specificity  Develop scanning technique for the OCT probe in such a small area  Spatial registration of RS and OCT data sets  Obtaining material for tests

Primary Design  Forward facing  Electrostatic scanning probe for OCT component  Located in the center  Fiber-optic array for RS component 300 um 270 um 125 um inner diam

 125 µm diameter single mode fiber illuminates and detects elastic scattering in the area of interest  Fiber placed in 60 µm outer diameter platinum alloy coil  Placed in the center of 400 µm diameter lumen of a triple lumen catheter  Two peripheral lumens contain 50 µm diameter wires  Electrode and ground leads  Driven by DC power supply, <5 µA,1-3 kV  1310 nm light source – broadband  Dissipative Polymer - dictates scanning time  Surface resistivity of 10 6 – Ω /square Electrostatic OCT component Munce, N.R. and Yang, V.X.D. et al. (2008).

Electrostatic OCT Component Platinum coil wrapped around fiber Ground electrode Electrode Ground wire Polymer block

Electrostatic OCT component  Electrostatic driven cantilever to create a compact, wide angle, rapid scanning forward viewing probe 1. Cantilever is neutral and is attracted to electrode 2. Cantilever touches electrode and acquires the same potential 3. Charge dissipates through the polymer from the cantilever and repels from electrode 4. Cantilever touches ground and becomes neutral again 5. Process restarts enacting a scanning motion

Fiber Optic Array RS Component  Multi-mode fibers (200 µm)set on either side of the OCT scanning fiber  One narrow band (785 nm) light sources on one side Light source Collection Highest concentration of collection OCT

Secondary Design  Replace the electrostatic scanning technique for the OCT component with a piezoelectric scanning technique.  Scanning range – mm depending on the voltage  Voltage – V  Frequency-110 Hz (resonance frequency)  Raman component will remain the same

Future work  Modify prototype  Test prototype  Evaluate effectiveness  Improve Raman design by adding more collection fibers  Modifying SolidWorks 3D design  Prepare poster presentation

Current Progress  Movement in electrostatic and piezoelectric OCT component  Needs to be quantified  Pictures are to be added to the website

References  Patil, C.A. (2009). Development combined raman spectroscopy-optical coherence tomograpgy for the detection of skin cancer. Disertation submitted to faculty of Graduate school of Vanderbilt University.  Munce, N.R. and Yang, V.X.D. et al.(2008). Electrostatic forward-viewing scanning probe for doppler optical coherence tomography using a dissipative polymer catheter. Optical letters, 33, 7,

Questions?

Specific Aims 1. Combine RS-OCT techniques into a fiber optic device to replace sample arm of current probe 2. Maximize Raman detection time efficiency 3. Integrate multi-mode and single-mode fibers into probe without compromising RS-OCT functionality

Raman Spectroscopy  Inelastic scattering (Stokes and Anti-Stokes)  Occurs 1 in 10 million compared to elastic  Frequency of light scattered from a molecule dependent on structural characteristics of molecular bonds  Able to determine malignant from non-malignant tissue  Gives no spatial information  All sorts of epithelial diseases Raman Shift (cm -1 ) = f ( ) – f ( ) 1 0

Optical Coherence Tomography (OCT)  Sensitivity to microstructural features of disease  Measures tissue reflectivity as function of depth  Detects elastic scattering  Ability to image over transverse areas of tissue of greater than 5mm  Micron scale resolution (>25µm)  Real-time speed