Transcript Microcavity Lasers for Cancer Cell Detection

Microcavity lasers for cancer
cell detection
Aaron Gin
Katie Mayes
Will McBride
Ryan McClintock
ME 381
Final Project
December 12, 2002
Presentation outline
Introduction and motivation
 Theoretical considerations
 Fabrication process
 Alternatives and future work

Microcavity lasers for cancer cell detection
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Motivation and applications
What is Cancer?
 Who is at risk?
 How is cancer traditionally detected?
 The need for instantaneous
classification of cells
 The Bio-Cavity laser concept
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Microcavity lasers for cancer cell detection
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What is cancer?
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Microcavity lasers for cancer cell detection
Occasionally cells die
or wear out, new cells
then grow to replace
them.
Sometimes when cells
reproduce, mistakes
are made in the code
than controls cell
reproduction.
This causes cell
growth to proceed out
of control, forming a
tumor.
www.cancer.ie
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Who is at risk?

Microcavity lasers for cancer cell detection
Slightly less than
50% of men and
more than 33% of
women will
experience some
form of cancer
during their lives.
American Cancer Society. Facts and Figures 2002
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How is cancer traditionally
detected?

Normal prostate
Prostate with
cancerous
growth
Biopsy needle
inserted into a
suspicious lump
on wall of colon
Microcavity lasers for cancer cell detection
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Biopsy: requires a
large sample of cells
be surgically removed
 Count cancer cells
 Flow Cytometry
Biological markers:
look for signs
(typically antigens)
produced by the body
in response to a
specific cancer.
www.cancer.med.umich.edu
www.rsna.org
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How is cancer traditionally
detected?
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Flow-Cytometry
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Bench top flow-cytometer
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Schematic diagram of flow-cytometer
Microcavity lasers for cancer cell detection
Powerful research
tool capable of
detection cancer.
Uses florescence,
scattering, and
transmission to
analyze cells
suspended in a
laminar fluid flow.
http://www.cancer.umn.edu/page/docs/fcintro.pdf
NASA, Cancer Detection Device, SpinOff (1998)
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Need for instantaneous
classification of cells

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Knowing how much to cut is
especially important when
removing delicate brain material.
Microcavity lasers for cancer cell detection
No instantaneous method
for determining if a cell is
cancerous currently exist.
Surgeons can only guess
how much material must be
removed
Samples of removed
material must be sent to a
lab; the patient is already
recovering by the time the
results are returned
www.msnbc.com
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The Bio-Cavity Laser concept
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Microcavity lasers for cancer cell detection
Incorporates cells directly
into the lasing process.
A micropump pushed cells
through tiny channels in
the active region of the
device.
The active region is
pumped by an external
laser source
Data is collected and
processed by a minispectrometer and
computer.
www.sandia.gov. News Releases. March 23, 2000
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The Bio-Cavity Laser concept
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Microcavity lasers for cancer cell detection
Cancer cells contain more
protein, and larger
nucleuses.
Their additional density
changes (by refractive
index) the speed of the
laser light passing through
them.
This modulates the
effective cavity length.
Creates a small difference
in lasing wavelength
www.sandia.gov. News Releases. March 23, 2000
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Why MEMS?

Convenience
User
 Patient

Cost Effective
 Integration with surgical tools
 Laser cavity needs to be on the
order of cell size
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Microcavity lasers for cancer cell detection
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Optically-pumped VCSEL
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Vertical Cavity Surface Emitting Laser (VCSEL)
Input from pump laser
VCSEL output
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Glass or semiconductor substrate
Theory overview
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Active layer
Upper and lower
mirrors
Channel or cavity
Upper mirror
AIR
Channel region
Active layer
Lower mirror
Substrate material
Microcavity lasers for cancer cell detection
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Optical pumping
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Frequency of emitted
photon
E
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
h
• ν is frequency
• ΔE is energy gap
• h is Planck’s constant
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Population Inversion
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More electrons in E2 than
E1
Necessary for lasing
Microcavity lasers for cancer cell detection
a
b
E3
E3
E2
E2
E1
c
E1
d
E3
E3
E2
E1
E2
E1
Adapted from Kasap
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Quantum wells
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Active layer can be bulk GaAs or InGaAs,
a single quantum well (SQW), or multiple
quantum wells (MQW)
MQW increases efficiency
Active Layer Barrier Layer
E(conduction band)
E
E(valence band)
Adapted from Kasap
Microcavity lasers for cancer cell detection
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Top and bottom mirrors
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Bragg Reflectors
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Alternating layers of high and low index of refraction
materials
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n1 d1  n2 d 2 
2
• n1,n2 are index of refractions of material 1&2
• d1,d2 are thicknesses of material 1&2
• λ is the wavelength of the emitted photons
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Top: must be transparent to pump wavelength
Bottom: must be lattice-matched to active layer
for good epitaxial growth
Microcavity lasers for cancer cell detection
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Cavity length
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Distance between top and bottom mirrors
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L = ½nλ
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Includes thickness of active layer and cavity
L is cavity length
n is an integer
λ is the output wavelength of the laser
Necessary for lasing, also alludes to
output dependence on the body in the
cavity
Microcavity lasers for cancer cell detection
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Dependence on cell shape
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Dielectric Sphere Case
2
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4 n  x10  x00  L 
p
 
d


• Δλ is wavelength shift
• ξ geometrical factor of the
•
•
•
•
•
sphere, ≤1
n is refractive index
xln nth 0 of the lth Hankel
function
L is effective cavity length
p is longitudinal mode
index
d is diameter of sphere
Microcavity lasers for cancer cell detection
d=6 μm (bottom), 10 μm (middle)
and 22 μm (top)
From Meissner, et al.
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System overview
Photodetector
Beam Splitter #2
Display
Spectrometer
Beam Splitter #1
Mirrors
Focusing Lens
Pump Laser
Analysis Region
Cavity
Adapted from P.L. Gourley, U.S. Pat. #5793485
Microcavity lasers for cancer cell detection
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Fabrication summary
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MBE or MOCVD growth of laser gain
medium (VCSEL).
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Machining of substrate to obtain fluidic
channels and laser microcavity.
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Wafer bonding to glass and top Bragg
reflector.
Microcavity lasers for cancer cell detection
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Fabrication process
GaAs or InP Substrate
Microcavity lasers for cancer cell detection
Paul L. Gourley, U.S. Patent No. 5793485 (1998).
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Fabrication process
Lower distributed Bragg
mirror
AlAs/Al0.2Ga0.8As (28.5
periods)
Grown by MBE or MOCVD
Molecular beam epitaxy system
Microcavity lasers for cancer cell detection
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Fabrication process
Laser Gain region
GaAs/InGaAs multiple
quantum wells
Grown by MBE or MOCVD
Metal-organic chemical vapor deposition system
Microcavity lasers for cancer cell detection
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Fabrication process
Insulating material
deposition by PECVD
Typically SiO2 or Si3N4
Will serve as laser cavity
and microchannels
Plasma-enhanced chemical vapor
deposition system
Microcavity lasers for cancer cell detection
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Fabrication process
Photolithography step to
define cavity and
microchannels
BOE or CH4 to remove SiO2
SF6 dry etch to remove Si3N4
Electron cyclotron resonance reactive ion
etcher
Microcavity lasers for cancer cell detection
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Fabrication process
Wafer bond semiconductor or
Pyrex with deposited Bragg
mirror to VCSEL base
Fusion Bonder
www.nanotech.ucsb.edu
Semiconductor or Pyrex
Microcavity lasers for cancer cell detection
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Microcavity laser including
microfluidic channels
Laser excitation pulse
Flush Channel
1
Processing
Reservoir
Inlet
Channel
Outlet
Channel
Analysis Region
1
Staging
Area
Valves
Processing
Reservoir
2
2
Reagent
Reservoir
Adapted from P.L. Gourley, U.S. Pat. #5793485
Microcavity lasers for cancer cell detection
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Miniaturized Optics for
Imaging Pre-cancer
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Miniaturized Optic Table (MOT)
 Image sensor
 Collector mirror
 Light source
 Scanning grating
 Folding-flat mirror
 Dichroic beam-splitter
 Lithographically printed
refractive lenses
 “Lean-to” folding flat mirror
 Objective lens
Microcavity lasers for cancer cell detection
C. P. Tigges, et. al., IEEE Journal of Quantum Electronics 38, 2 (2002).
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Miniaturized Optical Table
(MOT)
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Microcavity lasers for cancer cell detection
Note the silicon spring
V-shaped channel
Spring displacement
Stress in normal direction
150m thick optical
element
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Miniaturized Microscope
Objective
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Schematic
 Microscope Objective
 MOT micromachined
substrate
 Note: lenses in slots
Microcavity lasers for cancer cell detection
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Patterning of Optics: Binary
Photomask
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Lithographically
patterned
Binary photomask
 Black
 White
Hybrid glass
material
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150 m thick glass
substrate
Older element:
17.8m thick
hybrid material
Recent element:
34m thick hybrid
material
Microcavity lasers for cancer cell detection
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Patterning of Optics:
Greyscale Photomasks
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Microcavity lasers for cancer cell detection
Greyscale photomask
 Decreased
polymerization
 Lenslet array
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Future work
Need reliable methods of
transporting fluids into and out of
the semiconductor wafer.
 Biocompatibility of MEMS and optical
devices needs to be addressed.
 Need to collaborate with real
surgeons to demonstrate feasibility
in real operating environment
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Bibliography
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P.L. Gourley, J.D. Cox, J.K. Hendricks, A.E. McDonald G.C. Copeland, D.Y. Sasaki, M. Curry, and S.L. Skirboll,
“Semiconductor Microcavity Laser Spectroscopy of Intracellular Protein in Human Cancer Cells” Proc. SPIE, 4265,
113-124 (2001).
T. French, P.L. Gourley, and A.E. McDonald, “Optical properties of fluids in microfabricated channels” Proc. SPIE,
2978, 123-128 (1997).
P.L. Gourley and A.E. McDonald, “Semiconductor microlasers with intracavity microfluidics for biomedical
applications” Proc. SPIE, 2978, 186-196 (1997).
M.F. Gourley and P.L. Gourley, “Integration of Electro-Optical Mechanical Systems and Medicine: Where are we and
Where can we go?” Proc. SPIE, 2978, 197-204 (1997).
Paul L. Gourley, “Resonant-cavity apparatus for cytometry or particle analysis” U.S. Patent No. 5793485, 36 pp.
(1998).
American Cancer Society. Facts and Figures 2002
NASA, Cancer Detection Device, SpinOff (1998) (http://www.sti.nasa.gov/tto/index.html)
S.O. Kasap, Optoelectronics and Photonics: Principles and Practices, Prentice Hall, Upper Saddle River, NJ, 2001
K. E. Meissner, P. L. Gourley, T. M. Brennan, B. E. Hammons, and A. E. McDonald, “Intracavity spectroscopy in
vertical cavity surface-emitting lasers for micro-optical-mechanical systems,” Applied Physics Letters, vol 69 (11), 9
Sept. 1996
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Thank you!
Any questions?
Microcavity lasers for cancer cell detection
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