John Gohring

SERS-based detection in an optofluidic ring resonator platform

The development of surface enhanced Raman scattering (SERS) detection has made Raman spectroscopy relevant for highly sensitive labon- a-chip bio/chemical sensors. Despite the tremendous benefit in specificity that a Raman-based sensor can deliver, development of a lab-on-a- chip SERS tool has been limited thus far. In this work, we utilize an optofluidic ring resonator (OFRR) platform to develop a SERS-based detection tool with integrated microfluidics. The liquid core optical ring resonator (LCORR) serves both as the microfluidic sample delivery mechanism and as a ring resonator, exciting the metal nanoclusters and target analytes as they pass through the channel. Using this OFRR approach and R6G as the analyte, we have achieved a measured detection limit of 400 pM. The measured Raman signal in this case is likely generated by only a few hundred R6G molecules, which foreshadows the development of a SERS-based lab-on-a-chip bio/chemical sensor capable of detecting a low number of target analyte molecules.

Label free detection of CD4+ and CD8+ T cells using the optofluidic ring resonator.

We have demonstrated label free detection of CD4+ and CD8+ T-Lymphocyte whole cells and CD4+ T-Lymphocyte cell lysis using the optofluidic ring resonator (OFRR) sensor. The OFRR sensing platform incorporates microfluidics and photonics in a setup that utilizes small sample volume and achieves a fast detection time. In this work, white blood cells were isolated from healthy blood and the concentrations were adjusted to match T-Lymphocyte levels of individuals infected with HIV. Detection was accomplished by immobilizing CD4 and CD8 antibodies on the inner surface of the OFRR. Sensing results show excellent detection of CD4+ and CD8+ T-Lymphocyte cells at medically significant concentrations with a detection time of approximately 30 minutes. This work will lead to a rapid and low-cost sensing device that can provide a CD4 and CD8 count as a measure of HIV progression.

Versatile waveguide-coupled optofluidic devices based on liquid core optical ring resonators

A versatile waveguide-coupled optofluidic device using the liquid core optical ring resonator (LCORR) that can be operated with liquid of any refractive index (RI) is theoretically analyzed and experimentally demonstrated. The results confirm the confinement of resonant modes for all sample RIs, and reveal that confined modes in a high-RI core are excited by an external waveguide by resonant tunneling through the LCORR wall. It is further found that a thin wall must be used for effective interaction between the core mode and the waveguide. The results have important applications in optofluidic devices, including sensors, microfluidic lasers, and nonlinear optics.

Applications of the liquid core optical ring resonator platform

The liquid core optical ring resonator (LCORR) integrates an array of optical ring resonators into a microfluidics channel. The LCORR is made of a micro-sized glass capillary; the circular cross-section of the capillary acts as an optical ring resonator while the resonating light interacts with the fluid sample passing through the core. Q-factors larger than 107 have been achieved in LCORRs on the order of 100 micrometers in diameter. This implies an effective interaction length between the evanescent field of the resonator and the fluidic core of over 10 cm. The novel integrated architecture and excellent photonic performance lead to a number of applications in sensing, analytical chemistry, and photonics. For the last decade, optical ring resonators have been explored for label-free bio/chemical detection. The LCORR architecture possesses the same capabilities as other optical ring resonator bio/chemical sensors while also integrating micro-capillary-based fluidics with the sensor head. The integrated fluidics design in combination with the micro-sized sensor head and pico-liter sample volume lead to a lab-on-a-chip sensor for biomolecules, such as biomarkers and specific DNA sequences. Also, because the ring resonator creates a high-intensity field inside the microfluidic channel, the LCORR is an excellent microfluidic platform for surface-enhanced Raman scattering (SERS) detection in silver colloids. Finally, the high quality factor of the capillary-based resonator enables novel opto-fluidic devices, such as dye lasers. We will discuss the details of these concepts and present our research results in each of these applications.

Detection of CD4+ and CD8 + T-lymphocytes with the optofluidic ring resonator (OFRR) biosensor

We have demonstrated the use of the Opto-Fluidic ring resonator (OFRR) to achieve the label-free detection of CD4+ and CD8+ T-Lymphocytes. The OFRR sensing technology combines microfluidics and optical sensing in a small platform that achieves rapid detection. In this work, white blood cells were obtained from healthy blood and the concentration altered to reflect CD4 and CD8 concentrations of HIV infected individuals. The OFRR was modified to effectively capture these receptors located on T-Lymphocytes and obtain a sensing signal through interaction with an evanescent field. Results show isolation of CD4+ and CD8+ T-Lymphocytes at medically significant levels. This work will lead to a device that can provide a CD4 and CD8 count to measure HIV progression in a low cost sensing setup.

A universal label-free biosensing platform based on opto-fluidic ring resonators

Rapid and accurate detection of biomolecules is important for medical diagnosis, pharmaceuticals, homeland security, food quality control, and environmental protection. A simple, low cost and highly sensitive label-free optical biosensor based on opto-fluidic ring resonator (OFRR) has been developed that naturally integrates microfluidics with ring resonators. The OFRR employs a piece of fused silica capillary with a diameter around 100 micrometers. The circular cross section of the capillary forms the ring resonator and light repeatedly travels along the resonator circumference in the form of whispering gallery modes (WGMs) through total internal reflection. When the capillary wall is as thin as a couple of micrometers (< 4 μm), an evanescent field of the WGMs exists at the OFRR inner surface and interacts with the sample when it flows through the OFRR. In order to detect the target molecules with high specificity, the OFRR inner surface is functionalized with receptors, such as antibodies, peptide-displayed bacteriophage or oligonucleotide DNA probes. The WGM spectral position shifts when biomolecules bind to the OFRR inner surface and change the local refractive index, which provides quantitative and kinetic information about the biomolecule interaction near the OFRR inner surface. The OFRR has been successfully demonstrated for detection of various types of biomoelcuels. Here, we will first introduce the basic operation principle of the OFRR as a sensor and then application examples of the OFRR in the detection of proteins, disease biomarkers, virus, DNA molecules, and cells with high sensitivities will be presented.

Lab-on-a-chip bio/chemical sensing system based on the liquid core optical ring resonator

The liquid core optical ring resonator (LCORR) sensor is a newly developed capillary-based ring resonator that integrates microfluidics with photonic sensing technology. The circular cross-section of the capillary forms a ring resonator that supports whispering gallery modes (WGM), which interact with the sample as it passes through the capillary. As in previous ring resonator sensor implementations, the interaction between the WGM evanescent field and the sample enables label-free detection. With a prototype of an LCORR sensor, we have achieved a refractive index detection limit of 10-6 RIU and a detection limit for protein of 2 pg/mm2. Several engineering developments have been accomplished as well, including a thermal noise characterization, a thermal stabilization implementation, integration of the LCORR with a planar waveguide array, and electro-kinetic sample delivery. In the near future, the LCORR will be integrated into a dense 2-dimensional sensing array by integrating multiple capillaries with a chip-based waveguide array. This lab-on-a-chip sensing system will have a number of applications, including environmental sensing for defense purposes, disease diagnostics for medical purposes, and as a lab tool for analytical chemistry and molecular analysis.

Detection of HER2 breast cancer biomarker using the optofluidic ring resonator biosensor

In this work, we describe a novel approach for detecting the HER2/neu extra-cellular domain (ECD) protein in human serum samples using the opto-fluidic ring resonator (OFRR). OFRR sensing technology that incorporates microfluidics and optical sensing methods to achieve rapid label free detection in a small and low cost platform. In this study, HER2 proteins were spiked in PBS running buffer and serum at varying concentrations. Concentrations of the HER2 protein were adjusted in serum to levels typical of breast cancer patients that show over-expression of this particular beast cancer biomarker. The OFRR was modified with a biologically functional layer to efficiently capture the HER2 biomarker and produce a sensing signal through interaction with the evanescent field of the optical resonator. Results show effective capture of HER2 at medically relevant concentrations in serum and was achieved for concentrations as low as 13 ng/mL and ranged to above 100 ng/mL. This work will lead to a device that can be used as a tool for monitoring disease progression in a low cost sensing setup.

Development of versatile waveguide-coupled optofluidic micro-ring resonator devices

Optical ring resonators have been investigated for a number of interesting devices, including dye lasers and sensors. However, in general, these devices can only operate on liquid samples with a low refractive index (RI) because the whispering gallery modes (WGMs) are bound in the resonator through total internal reflection at the resonator/sample boundary. We recently introduced a new opto-fluidic ring resonator (OFRR) that uses a thin-walled capillary to deliver the sample through an array of ring resonators contained within the circular cross-section of the capillary. Thus, in the OFRR, the WGM is bound at the outer surface while the evanescent field interacts with the sample at the inner surface. Therefore, the OFRR can operate on samples of lower and higher RI than the capillary material. This unique feature, in combination with the OFRRs practical fluidic delivery design and its simplicity make it an attractive opto-fluidic device for sensors, lasers, and other applications. We analyze the OFRRs capability to support WGMs that are excited externally through fiber tapers and that interact with the sample inside. Using a quantum mechanical analogy, we show that for liquid cores with a higher RI than the capillary material, two coupled propagating waves exist that enable WGMs inside the liquid core to be excited by a fiber taper outside the OFRR, across a few microns. We experimentally verify our analysis by demonstrating refractometric sensors and dye lasers with core RIs lower and higher than the capillary.

Demonstration of composite signal enhancement from surface enhanced Raman spectroscopy in a liquid core optical ring resonator

Surface enhanced Raman spectroscopy (SERS) utilizing silver colloids for localized plasmonic enhancement has been heavily researched due to its tremendous increase in the Raman signal of bio/chemical molecules. We demonstrate further enhancement by multiplying the SERS effect by the resonant enhancement of a ring resonator microcavity. The liquid core optical ring resonator (LCORR) offers a high-performance and practical design to obtain this composite enhancement for bio/chemical molecule detection. The LCORR integrates an array of optical ring resonators into a capillary-based microfluidic channel to form a novel bio/chemical sensing platform. The circular cross-section of the glass capillary acts as an optical ring resonator, with the evanescent field of the resonant light interacting with the sample passing through the capillary. The LCORR has already been well-studied for applications in label free biomolecule sensing. In this work, we utilize a silver colloid solution inside the capillary to perform SERS-based detection. In contrast to a typical SERS system where the incident light interacts with the colloid and target molecules only once, in the LCORR system, the tightly confined light resonates around the capillary wall, repeatedly interacting with the SERS system. Our experimental results show the increased enhancement due to the composite effect of the cavity resonance and the localized plasmonic effect of the nanoparticles inside the cavity. We have achieved detection of 3.3 nM R6G inside the LCORR. In addition to the excellent sensitivity, this detection system represents an advancement in the development of practical SERS bio/chemical sensors due to the arrayed nature of the sensors combined with the integrated microfluidics of the LCORR.