Biosensing with silicon chip based microcavities Warwick Bowen

Co-workers PhD Students Collaborators 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 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)]

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: In development: For the future: 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. 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. Complimentary to DNA microarrays/ SPR arrays (Biacore).

Photonics and optical microresonators Q-V V: 75 mm3 Q: 5×108 Q: 107 V: 300 mm3 [Vahala et al., Nature 424 839 (2003)]