Biosensing with silicon chip based microcavities
Warwick Bowen
Co-workersPhD StudentsJacob ChemmannoreMatthew McGovernTerry McRaeJian Wei Tay
CollaboratorsTobias Kippenberg (Max Planck)Jeff Kimble (Caltech)Kerry Vahala (Caltech)
Aims 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.
Motivation• 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…
Light-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.
Light-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.
Current 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– …
Current 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.
Optical 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 quantumelectrodynamics.
• Preliminary investigations into molecular detection by Vollmer et al.
[Vollmer et al., Appl. Phys. Lett. 80, 4057 (2002)][Arnold et al., Opt. Lett. 28, 272 (2003)]
Optical 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.
[Vollmer et al., Appl. Phys. Lett. 80, 4057 (2002)][Arnold et al., Opt. Lett. 28, 272 (2003)]
Optical microcavity based biosensing
• Interaction of protein molecule with evanescent field polarisesmolecule, alters local refractive index experienced by WGM.
• Causes optical path length change.
• Detected as shift in opticalresonance frequencies.
• No molecular labels are required.• The surface of microsphere
sensitisable – adsorbs onlyspecific proteins.
Optical 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.
– Q~106, V~3000 m3.
[Vollmer et al., Appl. Phys. Lett. 80, 4057 (2002)]
Optical 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 > 15 BSA.
[Vollmer et al., Appl. Phys. Lett. 80, 4057 (2002)]
Optical microcavity based biosensing
• To achieve single molecule detection need better microcavities.
• Vollmer’s V limited by:– Microsphere geometry.– Optical wavelength (1300 nm).– Fabrication issues.
• Vollmer’s 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)]
• 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 m 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 resultingmicrotoroid to be exceptionallysmooth.
[Armani et al., Nature 421, 925 (2003)]
Microtoroids
[Armani et al., Nature 421, 925 (2003)]
Microtoroids
• Smaller mode volumes due to azimuthal mode compression.
• For large compression, toroid mode identicalto mode of single mode fiber.
• Very efficient coupling achievable using tapered fibers (>99.5%).
Microtoroids
[Kippenberg et al., Appl. Phys. Lett. 83, 797 (2003)]
• Smaller mode volumes due to azimuthal mode compression.
• For large compression, toroid mode identicalto mode of single mode fiber.
• Very efficient coupling achievable using tapered fibers (>99.5%).
Microtoroids
[Kippenberg et al., Appl. Phys. Lett. 83, 797 (2003)]
• Smaller mode volumes due to azimuthal mode compression.
• For large compression, toroid mode identicalto mode of single mode fiber.
• Very efficient coupling achievable using tapered fibers (>99.5%).
• V’s as small as 75 m3 and Q‘s as high as 5·108 (finesse > 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.
Microtoroids 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 totalmode volume reduction possible.
Microtoroids 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.
Microtoroids for biosensing
Where 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!– ...
Cavity quantum electro-dynamics with microtoroids• First demonstration of strong coupling between a single
atom and a single photon in a monolithic optical resonator.
[Aoki et al., Nature 443, 671 (2006)]
Single atom detection events
• 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).
Conclusion
Photonics and optical microresonators
• Q-V
[Vahala et al., Nature 424 839 (2003)]V: 75 m3Q: 5×108Q: 107
V: 300 m3Q: 5×108