Title: Biosensing with silicon chip based microcavities
1Biosensing with silicon chip based microcavities
2Co-workers
PhD Students Jacob Chemmannore Matthew
McGovern Terry McRae Jian Wei Tay Collaborators
Tobias Kippenberg (Max Planck) Jeff Kimble
(Caltech) Kerry Vahala (Caltech)
3Aims of research
- Broad goal apply experience in
- quantum/atom optics to current biophotonics
problems. - Aim implement novel and effective solutions.
- Specific short and medium term goals in two
areas - Biophotonic applications of ultrahigh Q optical
microcavities used in cavity QED experiments. - Quantum limits of particle position measurement
with optical tweezers.
4Motivation
- Great need for highly sensitive biosensing
- techniques
- Fundamental contribution to the understanding of
- DNA binding
- Protein conformational changes
- Molecular motors
- Cellular processes
- Ion channels
- Pharmacological and biological diagnosis
applications - Enhance control and understanding of biochemical
processes leading to greater yields - Small molecule aspects of drug design
- Detect biological pathogens, drugs, chemicals
5Light-matter interaction
- Interaction of light and matter primarily due to
optical electric field coupling to electric
dipoles in matter. - Determines all major atom-light phenomena
(refraction, absorption, Rayleigh scattering,
Raman scattering, fluorescence). - In biophotonic sensing systems, typically want to
maximise interaction strength - Especially for single molecule detection.
6Light-matter interaction
- Strength of interaction determined by
- Increase by enhancing either d or E.
- Typically
- For E confine optical field to small volume, and
increase intensity (e.g. high NA lens,
femtosecond pulses). - For d label the molecule with a fluorophore or
metallic nano or micro-scale sphere.
7Current biosensing systems
- Many biological imaging and manipulation systems
based on such enhancements - Scanning near-field optical microscopes (SNOMs)
- Surface enhanced Raman spectrometers (SERS)
- Surface plasmon resonance imaging systems (SPR)
- Evanescent wave induced fluorescence
spectrometers - Confocal fluoresence microscopes
- Optical tweezers
8Current biosensing systems
- However, in terms of the long standing goals of
single small molecule detection, observation, and
manipulation the usefulness of such techniques
still relatively limited. - Techniques with resolution capable of single
molecule detection currently - Rely on molecular labels which can be difficult
to attach in practice, and can affect observed
behaviour. - Are not real-time, or have temporal resolution in
the seconds to milliseconds regime, and therefore
cannot capture the fast dynamics of molecules
such as molecular motors, and of molecular
binding.
9Optical microcavity based biosensing
- New techniques needed to provide further insight
into single molecule dynamics. - Interaction strength can be enhanced beyond what
is presently possible by confining light not only
spatially, but also temporally. - Achieved in optical microcavities
- used in cavity quantum
- electrodynamics.
- Preliminary investigations into
- molecular detection by
- Vollmer et al.
Arnold et al., Opt. Lett. 28, 272 (2003)
Vollmer et al., Appl. Phys. Lett. 80, 4057
(2002)
10Optical microcavity based biosensing
- Focus on microsphere cavities
- Light resonates via total internal
- reflection in WGMs.
- Part of the WGM located outside
- microsphere in exponentially
- decaying evanescent field.
- Optical taper coupling.
- Sharp spectral resonances when
- optical path length equals integer
- number of optical wavelengths.
Arnold et al., Opt. Lett. 28, 272 (2003)
Vollmer et al., Appl. Phys. Lett. 80, 4057
(2002)
11Optical microcavity based biosensing
- Interaction of protein molecule
- with evanescent field polarises
- molecule, alters local refractive
- index experienced by WGM.
- Causes optical path length
- change.
- Detected as shift in optical
- resonance frequencies.
- No molecular labels are required.
- The surface of microsphere
- sensitisable adsorbs only
- specific proteins.
12Optical microcavity based biosensing
- Minimum detectable molecule size determined by
polarisability of molecule and optical electric
field strength. - Optical electric field maximised by
- Maximising Q of optical resonance (hence
ultrahigh Q). - Minimising V of optical field (hence
microcavity). - Vollmer
- Silica microspheres immersed in water.
- Q106, V3000 ?m3.
Vollmer et al., Appl. Phys. Lett. 80, 4057
(2002)
13Optical microcavity based biosensing
- They
- Experimentally demonstrated bulk detection of
specific proteins (BSA). - Predicted adsorption of as few as 6000 BSA
protein molecules was detectable. - Larger protein molecules (typically) have larger
induced dipoles. - Detection of smaller numbers possible.
- However, rare to find proteins with molecular
weight ?gt 15? BSA.
Vollmer et al., Appl. Phys. Lett. 80, 4057
(2002)
14Optical microcavity based biosensing
- To achieve single molecule detection need better
microcavities. - Vollmers V limited by
- Microsphere geometry.
- Optical wavelength (1300 nm).
- Fabrication issues.
- Vollmers Q limited primarily by optical
absorption of water - High at 1300 nm.
- Overcome these limits with new type of optical
microcavity, the microtoroid.
Armani et al., Nature 421, 925 (2003)
15Microtoroids
- WGM type ultrahigh Q optical microcavities
similar to microspheres. - As the name suggests, the geometry is toroidal
rather than spherical. - Reproducibly lithographically fabricated
- Etch 20-120 mm diameter circular SiO2 pad on
silicon wafer. - Etch away Silicon with XeF2 to produce a SiO2
disk on a pedestal. - Produce toroid by melting disk
- with a CO2 laser.
- Surface tension causes the
- surface of the resulting
- microtoroid to be exceptionally
- smooth.
Armani et al., Nature 421, 925 (2003)
16Microtoroids
- Smaller mode volumes due to azimuthal mode
compression. - For large compression, toroid mode identical
- to mode of single mode fiber.
- Very efficient coupling
- achievable using tapered fibers
- (gt99.5).
Armani et al., Nature 421, 925 (2003)
17Microtoroids
- Smaller mode volumes due to azimuthal mode
compression. - For large compression, toroid mode identical
- to mode of single mode fiber.
- Very efficient coupling
- achievable using tapered fibers
- (gt99.5).
Kippenberg et al., Appl. Phys. Lett. 83, 797
(2003)
18Microtoroids
- Smaller mode volumes due to azimuthal mode
compression. - For large compression, toroid mode identical
- to mode of single mode fiber.
- Very efficient coupling
- achievable using tapered fibers
- (gt99.5).
Kippenberg et al., Appl. Phys. Lett. 83, 797
(2003)
19Microtoroids for biosensing
- Vs as small as 75 ?m3 and Qs as high as 5108
(finesse gt 106) routinely achievable with 1550 nm
light in air. - 40? reduction in V and a 200? increase in Q c.f.
microspheres studied by Vollmer et al.. - However, when immersed in water, the quality is
predicted to drop to around 106 as a result of
optical absorption.
20Microtoroids for biosensing
- Use 532 nm light.
- Minimum absorption wavelength of water.
- Absorption coefficient four orders of magnitude
smaller than at 1550 nm. - Should not limit Q.
- Furthermore, microcavity dimensions ultimately
limited by the optical wavelength used. - Reduction from 1550 to 532
- nm should allow (1550/532)3 ?
- ? 25 times reduction in V.
- In principle 1000 times total
- mode volume reduction
- possible.
21Microtoroids for biosensing
- Optical microcavity based biosensor sensitivity
proportional to ratio Q/V. - Therefore potential for 1000 ? 200 200,000
times sensitivity improvement c.f. Vollmer
experiments. - Should easily facilitate the detection of single
molecules. - Aim of the microcavity research programme at
Otago - Fabricate microtoroids with this
- sort of sensitivity
- Use to detect single unlabeled
- molecules
- Study dynamics.
22Where we are currently
- Developed
- Laser reflow stage of microtoroid fabrication
- Optical fibre taper pulling setup
- Toroid/taper coupling setup
- In development
- Remaining steps of
- microtoroid fabrication
- Water immersion bath for
- bulk protein detection
- Laser frequency/taper
- position control systems
- For the future
- Single molecule detection!
- ...
23Cavity quantum electro-dynamics with microtoroids
- First demonstration of strong coupling between a
single atom and a single photon in a monolithic
optical resonator.
Single atom detection events
Aoki et al., Nature 443, 671 (2006)
24Conclusion
- Microtoroid based optical biosensors have
potential to facilitate detection and monitoring
of single biomolecules. - New insight into the dynamics of motor molecules,
and molecular binding processes. - Array of lithographically fabricated
microtoroids, each surface activated for a
particular biomolecule can be envisaged. - Such a system could be used to monitor the
concentration of multiple proteins/molecules in
real time - Quality control in water treatment
- systems.
- Early detection systems for biotoxins
- and biological warfare agents.
- systems.
- Complimentary to DNA microarrays/
- SPR arrays (Biacore).
25Photonics and optical microresonators
Vahala et al., Nature 424 839 (2003)