Whispering Gallery Mode Biosensing

Label-Free Detection down to Single Particles

Optical resonance is created by localizing coherent light within a micro or nanoscale structure so that it interferes constructively. Examples for such miniature optical resonators are silica microspheres and silicon photonic crystals. Because these optical resonators are almost immune to damping in a liquid, they are ultra sensitive biosensors: for example, single virus particles can be detected from discrete resonance frequency-shifts without requiring any chemical or fluorescent labeling of the particles. Sensitivity on the single particle level is possible due to the high quality (Q-) factor and the small size of the resonator.

Read the Nature Methods Perspective



Probing Molecular Conformation by Q-Enhanced Pump-Probe Spectroscopy

Optical microresonators with small modal volumes and high quality (Q) factors significantly enhance interaction of the optical field with the material through recirculation, which makes them exceptionally sensitive to the optical properties of the resonator and the surrounding medium. We use this attribute for biosensing, where binding of only a few molecules on the microcavity surface shifts the frequencies of the resonant modes that evanescently interact with the adsorbed material. Furthermore, a pump-probe spectroscopy is implemented where a visible optical pump centered at a molecular absorption band induces changes of molecular structure which are dynamically monitored with an infrared probe. Changes in molecular conformation and orientation can be determined from measurements with transverse-electric (TE) and -magnetic (TM) polarized resonant modes  0.5Å3 resolution. We demonstrate this approach by measuring orientation and polarizability changes of retinal in bacteriorhodopsin membranes. Our technique promises novel insights in biological signal transduction (e.g. by G-Protein coupled receptors) and in energy conversion by photosynthetic pigments.

Read the Biophysical Journal paper



Light Manipulation with Molecularly Functionalized Microcavities

Dynamic, photoinduced molecular transitions in a self-assembled bacteriorhodpsin (bR) monolayer are used to reversibly configure a micron-scale high-Q photonic circuit element in which the optical response is resonantly enhanced. The all-optical resonant coupler operates at the telecom frequencies (1,311/1,550 nm) and represents a unique bottom-up paradigm for fabrication of hybrid molecular-photonic architectures that employ ordered molecules for optical manipulation at small scales.

Light manipulation on the molecular level relies on changing the phase or the intensity of probing light as a result of interactions with molecular dipoles. Although the perturbation to an optical mode caused by a single molecule is negligible, the effect becomes more pronounced when the mode interacts with highly-organized molecular assemblies. In such anisotropic systems, the simplest of which is a molecular monolayer, the optical response is not obscured by local clustering and bulk averaging, and can therefore be tailored polarization and frequency specific. However, due to the extremely low optical density of these self-assembled monolayers (SAMs), the possibility of using them to effectively manipulate light at small scales has been uniformly ignored. Our experiments show that a biological SAM can perform a basic photonic switching function on a scale of a few hundreds of microns. All-optical signal routing between two optical fibers was achieved by using a high-Q optical microcavity to resonantly enhance interaction of the evanescent field of an optical mode with a bR monolayer. The demonstrated all-optical coupler operates in the frequency-domain, far from the bR absorption bands, which allows it to modulate intense near-IR probe beams with low-intensity visible pumps (< 200 µW).

Read the Applied Physics Letter paper.



Bacteria Detection and Biofilm Analysis

Microcavity sensors provide a useful tool to study biologically important surface coatings and biofilms which are formed from larger particles such as micrometer-sized bacteria. The established theory is then no longer valid since a form-factor is necessary to account for well-defined size, shape, refractive index profile and orientation of micron-sized bacterial particles; and one can no longer disregard scattering in the analysis. We develop theory that analyzes perturbations to optical microcavity sensors induced by random adsorption of bacteria. Theoretical results are confirmed in measurements taken with E.coli bacteria as model system, establishing the whispering gallery mode biosensor as sensitive technique for detection and analysis of micro-organisms.

Read the Optics Express paper.



Molecular Analysis by Micro-Optical Resonances

Read the review article: "Taking detection to the limit", B.I.F. Futura, Vol. 20, 239-244 (2005)

Ever since the pioneering work on high quality (Q) factor whispering gallery resonances in spherical micrometer sized resonators by Ashkin and Dziedzkic there have been a plethora of articles which have extended the measured “ultimate”Q to ~1010. The interest in optical resonators has been fueled by a diversity of areas from studies of strong coupling in quantum electrodynamics to ultra-sensitve biosensing [F.Vollmer et al, Appl. Phys. Lett., 80, 4057 (2002)]. The latter interest, which has produced a record sensitivity, depends on the shift in resonance frequency due to the perturbation by adsorbed nanoparticles (i.e. protein molecules, DNA, etc.).

We present an optical biosensor with unprecedented sensitivity for detection of unlabeled molecules. Our device uses optical resonances in a dielectric microparticle (whispering gallery modes) as the physical transducing mechanism. The resonances are excited by evanescent coupling to an eroded optical fiber and detected as dips in the light intensity transmitted through the fiber at different wavelengths. Binding of proteins on the microparticle surface is measured from a shift in resonance wavelength. We demonstrate the sensitivity of our device by measuring adsorption of bovine serum albumin and we show its use as a biosensor by detecting streptavidin binding to biotin.

The original work was done in collaboration with Dr. Stephen Arnold, Polytechnic University, Brooklyn.

Tuning through whispering gallery modes. A tapered optical fiber is running vertically through the image. A microsphere cavity is evanescently coupled to the fiber. Figure-8 shaped resonant modes are excited in the spheroidal cavity at different resonant frequencies.

Varying the coupling between the fiber and microsphere leads to the excitation of different resonant modes.





Integration of Fiber Optics, Microcavities and Microfluidics' Flow Sensor

There is great interest in the miniaturization of (bio)-chemical analysis systems for laboratory use as well as for biomedical point-of-care testing, which is driven by availability of simple, low-cost fabrication methods for microfluidic structures. The soft-lithography-based, microfluidic technology has already found numerous applications in lab-on-chips and in opto-fluidic devices. We are interested in controlling aqueous environment of microcavity sensors and photonic crystal devices by integration with microfluidic structure that allows for controlled sample delivery, multiplexing, high-throughput, as well as tuning of optical device property. To ensure accurate laminar flow operation and to implement closed-loop control it is often necessary to integrate flow sensors. Therefore, there is a need for low-cost, micron-sized flow sensors that can be fabricated using standard laboratory techniques. We present a robust optical flow sensor with wide dynamic range built from an optical fiber that can be integrated in a closed microfluidic channel of variable width. The sensing mechanism is based on displacement of a fiber-tip by microfluidic drag force which reduces the intensity of transmitted light. The dynamic range is adjustable by thinning the silica fiber-tip in a one-step chemical etch. Assembly is simple since alignment is guided by preformed, polymer-molded channels. We find that thin tapers are even sensitive to acoustic induced flow. A direction worth exploring would be the design of a microfluidic channel that allows for frequency separation, similar in design to the cochlea.

Read the Lab on a Chip paper.



Ring-Resonator for Chiral Discrimination

We investigate the use of optical resonators to observe chirality in molecules. This project is a collaboration with Peer Fischer. A chiral substance can occur in two mirror-image forms (enantiomers). Most biochemical reactions involve chiral molecules (e.g. aminoacids, nucleotides, carbohydrates) and interestingly only one of the two enantiomers is biologically active. We present an instrument based on an optical ring resonator that can discriminate chiral molecules. Different from any other optical technique, our approach analyses the chiral phenomenon in the frequency domain. The sensitivity of the ring resonator is independent of its size which makes it an ideal analytic component for a lab-on-a chip.

Read the Optics Letter paper.



Frequency-domain Microscopy and Precision Metrology using Ring Resonators

Ring resonators are in general not amenable to strain-free (non-contact) displacement measurements. We show that this limitation may be overcome if the ring resonator, here a fiber- loop, is designed to contain a gap, such that the light traverses a free-space part between two aligned waveguide ends. Displacements are determined with nanometer sensitivity by measuring the associated changes in the resonance frequencies. Miniaturization should increase the sensitivity of the ring resonator interferometer. Ring geometries that contain an optical circulator can be used to profile reflective samples or as components in optical data storage devices. With Peer Fischer

Read the Sensors and Actuators A paper.