Biosensing with silicon chip based microcavities

Warwick Bowen

Co-workers

PhD StudentsJacob Chemmannore

Matthew McGovern

Terry McRae

Jian 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 thesurface 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 m3

Q: 5×108Q: 107

V: 300 m3

Q: 5×108