Manoj M. Varma

Spinning-disk self-referencing interferometry of antigen–antibody recognition

A gold ridge microstructure fabricated to a height of lambda/8 on a high-reflectivity substrate behaves as a wave-front-splitting self-referencing interferometer in phase quadrature when illuminated by a Gaussian laser beam and observed in the far field along the optic axis. When immuno-gammaglobulin (IgG) antibodies are selectively immobilized on the gold microstructure, they recognize and bind to a specific antigen, which shifts the relative optical phase of the interferometer and modifies the far-field diffracted intensity. We detect bound antigen interferometrically on spinning disks at a sampling rate of 100 kHz and verify the interferometric nature of the signal by using two quadratures of opposite sign to rule out effects of dynamic light scattering. Strong molecular recognition is demonstrated by the absence of binding to nontarget molecules but strong signal change in response to a specific antigen. This BioCD has the potential to be applied as a spinning-disk interferometric immunoassay and biosensor.

Adaptive interferometry of protein on a BioCD

Adaptive spinning-disk interferometry is capable of measuring surface profiles of a thin biolayer with subnanometer longitudinal resolution. High-speed phase modulation in the signal beam arises from the moving surface height profile on the spinning disk and is detected as a homodyne signal via dynamic two-wave mixing. A photorefractive quantum-well device performs as an adaptive mixer that compensates disk wobble and vibration while it phase-locks the signal and reference waves in the phase quadrature condition (pi/2 relative phase between the signal and local oscillator). We performed biosensing of immobilized monolayers of antibodies on the disk in both transmission and reflection detection modes. Single- and dual-analyte adaptive spinning-disk immunoassays were demonstrated with good specificity and without observable cross-reactivity. Reflection-mode detection enhances the biosensing sensitivity to one-twentieth of a protein monolayer, creates a topographic map of the protein layer, and can differentiate monolayers of different species by their effective optical thicknesses.

Adaptive optical biocompact disk for molecular recognition

We report the use of adaptive interferometry to detect a monolayer of protein immobilized in a periodic pattern on a spinning glass disk. A photorefractive quantum-well device acting as an adaptive beam mixer in a two-wave mixing geometry stabilizes the interferometric quadrature in the far field. Phase modulation generated by the spinning biolayer pattern in the probe beam is detected as a homodyne signal free of amplitude modulation. Binding between antibodies and immobilized antigens in a two-analyte immunoassay was tested with high specificity and without observable cross reactivity.

Highly Sensitive Carbon Nanotubes Coated Etched Fiber Bragg Grating Sensor for Humidity Sensing

The sensing of relative humidity (RH) at room temperature has potential applications in several areas ranging from biomedical to horticulture, paper, and textile industries. In this paper, a highly sensitive humidity sensor based on carbon nanotubes (CNTs) coated on the surface of an etched fiber Bragg grating (EFBG) sensor has been demonstrated, for detecting RH over a wide range of 20%-90% at room temperature. When water molecules interact with the CNT coated EFBG, the effective refractive index of the fiber core changes, resulting in a shift in the Bragg wavelength. It has been possible to achieve a high sensitivity of ~31 RH, which is the highest compared with many of the existing FBG-based humidity sensors. The limit of detection in the CNT coated EFBG has been found to be ~0.03 RH . The experimental data shows a linear response of Bragg wavelength shift with increase in humidity. This novel method of incorporating CNTs on to the FBG sensor for humidity sensing has not been reported before.

Diffractive Optical Analysis for Refractive Index Sensing using Transparent Phase Gratings.

We report the implementation of a micro-patterned, glass-based photonic sensing element that is capable of label-free biosensing. The diffractive optical analyzer is based on the differential response of diffracted orders to bulk as well as surface refractive index changes. The differential read-out suppresses signal drifts and enables time-resolved determination of refractive index changes in the sample cell. A remarkable feature of this device is that under appropriate conditions, the measurement sensitivity of the sensor can be enhanced by more than two orders of magnitude due to interference between multiply reflected diffracted orders. A noise-equivalent limit of detection (LoD) of 6 × 10−7 was achieved with this technique with scope for further improvement.

Spotting 2D atomic layers on aluminum nitride thin films

Substrates for 2D materials are important for tailoring their fundamental properties and realizing device applications. Aluminum nitride (AIN) films on silicon are promising large-area substrates for such devices in view of their high surface phonon energies and reasonably large dielectric constants. In this paper epitaxial layers of AlN on 2″ Si wafers have been investigated as a necessary first step to realize devices from exfoliated or transferred atomic layers. Significant thickness dependent contrast enhancements are both predicted and observed for monolayers of graphene and MoS2 on AlN films as compared to the conventional SiO2 films on silicon, with calculated contrast values approaching 100% for graphene on AlN as compared to 8% for SiO2 at normal incidences. Quantitative estimates of experimentally measured contrast using reflectance spectroscopy show very good agreement with calculated values. Transistors of monolayer graphene on AlN films are demonstrated, indicating the feasibility of complete device fabrication on the identified layers.

High-speed label-free multianalyte detection through microinterferometry

Interferometers can detect optical path changes down to a billionth-lambda at the half intensity point at quadrature, (defined when the signal and reference waves are out of phase by ninety degrees). We have fabricated interferometric microstructures on silicon all operating at quadrature. The ultimate capability of this approach is the fabrication of over a billion interferometric biosensors on a single spinning disk having the capacity for mega-samples per second sampling speed. As an initial proof of principle of this technique, we have detected the presence of immobilized anti-mouse IgG and the specific binding of mouse IgG at a sampling rate of 100kiloSamp/sec, while non-specific binding observed was low. We will demonstrate that this technique provides a label-free method that may rapidly screen thousands of proteins per assay.

Spinning-disk laser interferometers for immuno-assays and proteomics: the BioCD

Spinning-disk self-referencing laser interferometers are being developed as high-speed high-sensitivity platforms for immunoassay and proteomics applications. Their compact disc (CD) formats have the potential for ultra-high-throughput multianalyte assays as well as for binding kinetics and quantitative analysis. Self-referencing interferometers are immune to mechanical variations, enabling interferometric sensitivities and speeds that are several orders of magnitude larger than for their counterpart fluorometric techniques. This paper defines for the first time three classes of the BioCD that differ in their method of self-referencing and reviews their relative merits and sensitivities. Each uses a near-field probe with far-field detection. The three classes are: microdiffraction, adaptive optical, and photonic cavity.

High precision measurement of intensity peak shifts in tunable cascaded microring intensity sensors

We demonstrate a method to precisely track intensity peak shifts in tunable cascaded double-microring based refractive index sensors. Without modifications, width of the intensity peak of a tunable cascaded microring device limits the precision of peak-shift measurements and thereby the limit of detection of the sensor. We overcome this limitation by using dual harmonic lock-in detection for precisely determining the position of the intensity maximum. Using this modification, we have demonstrated a reduction in the full width at half-maximum (FWHM) of the intensity peak by a factor of over 1300. We show that such a reduction in FWHM of the peak curve can significantly improve the detection limit of a tunable cascaded microring-based sensor.

Calibration of Etched Fiber Bragg Grating Sensor Arrays for Measurement of Molecular Surface Adsorption

Etched Fiber Bragg Grating (EFBG) sensors are attractive from the point of the inherently high multiplexing ability of fiber based sensors. However, the strong dependence of the sensitivity of EFBG sensors on the fiber diameter requires robust methods for calibration when used for distributed sensing in a large array format. Using experimental data and numerical modelling, we show that knowledge of the wavelength shift during the etch process is necessary for high-fidelity calibration of EFBG arrays. However as this approach requires the monitoring of every element of the sensor array during etching, we also proposed and demonstrated a calibration scheme using data from bulk refractometry measurements conducted post-fabrication without needing any information about the etching process. Although this approach is not as precise as the first one, it may be more practical as there is no requirement to monitor each element of the sensor array. We were able to calibrate the response of the sensors to within 3% with the approach using information acquired during etching and to within 5% using the post-fabrication bulk refractometry approach in spite of the sensitivities of the array element differing by more than a factor of 4. These two approaches present a tradeoff between accuracy and practicality.