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.
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.
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.
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 OFRR's practical fluidic delivery design and its simplicity make it an attractive opto-fluidic device
for sensors, lasers, and other applications.
We analyze the OFRR's 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.
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.
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.
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.
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