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Biosensing with silicon chip based microcavities Warwick Bowen Co-workers PhD Students Jacob Chemmannore Matthew McGovern Terry McRae Jian Wei Tay Collaborators Tobias 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 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)] 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. [Arnold et al., Opt. Lett. 28, 272 (2003)] [Vollmer et al., Appl. Phys. Lett. 80, 4057 (2002)] Optical 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. 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)] Microtoroids • 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 resulting microtoroid to be exceptionally smooth. [Armani et al., Nature 421, 925 (2003)] Microtoroids • 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 (>99.5%). [Armani et al., Nature 421, 925 (2003)] Microtoroids • 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 (>99.5%). [Kippenberg et al., Appl. Phys. Lett. 83, 797 (2003)] Microtoroids • 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 (>99.5%). [Kippenberg et al., Appl. Phys. Lett. 83, 797 (2003)] Microtoroids for biosensing • 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 total mode 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. 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 electrodynamics 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)] Conclusion • 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). Photonics and optical microresonators • Q-V Q: 107 Q: 5×108 V: 300 m3 Q: 5×108 V: 75 m3 [Vahala et al., Nature 424 839 (2003)]