Breast cancer is the most frequently diagnosed malignancy in women worldwide. Because of its great impact on
society, a lot of research funding has been used to develop novel detection tools for aiding breast cancer diagnosis
and prognosis. In this work, we demonstrated a simple, fast, and sensitive detection of circulating breast cancer
biomarker CA15-3 with opto-fluidic ring resonator (OFRR) sensors. The OFRR sensor employs a thin-walled
capillary with wall thickness less than 4 μm. The circular cross section of the capillary forms the optical ring
resonator, in which the light circulates in the form of whispering gallery modes (WGMs). The capillary wall is thin
enough that the evanescent field of the WGM extends into the capillary core and responds to refractive index
changes in the capillary core or close to its interior surface. The WGM spectral position will change when the
biomolecules bind to the surface, yielding quantitative and kinetic information about the biomolecule interaction.
Here, the direct immunoassay method was employed for the detection of CA15-3 antigen without any signal
amplification steps. The sensor performance in both PBS buffer and human serum were investigated, respectively.
The experimental detection limit was 5 units/mL in PBS buffer and 30 units/mL for CA15-3 spiked in serum, both
of which satisfied clinical diagnosis requirements. The potential use of the OFRR as the point-of-care device for
breast cancer detection was tested by measuring the CA15-3 level in blood samples collected from stage IV breast
cancer patients and the results were compared with standard clinical test.
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.
A rapid, label-free on-line virus detection method has been developed based on opto-fluidic ring resonator (OFRR). The OFRR employs a fused silica capillary with a diameter around 100 μm. The circular cross section of the capillary forms the ring resonator that supports the whispering gallery modes (WGMs). The OFRR wall is only a few micrometers. Thus, the evanescent field of the WGMs extends into the core and interacts with the sample flowing in the core. The WGM spectral position shifts in response to the binding of biomolecules to the OFRR inner surface, providing quantitative and kinetic information about the biomolecule interaction. In this work, M13 filamentous phage and anti-M13 antibody are chosen as a model system to demonstrate the detection and quantification of virus in liquid samples. Anti-M13 antibodies are first covalently attached on the aminosilane coated OFRR surface to provide a bioselective layer. The detection is then performed when the virus concentration varies from 1011 pfu/mL down to 103 pfu/mL. Our experimental results show that the OFRR is capable of detecting M13 at a concentration as low as 1000 pfu/mL. Control experiments are carried out to show the specificity of the detection. A theoretical model is developed to analyze the experimental results. The OFRR are advantageous in virus detection, as it integrates the ring resonator with fluidic channels and provides continuous on-line monitoring capability. It also has great potential for sensitive, rapid, and low-cost micro total analysis devices for biomolecule detection.
We report on the development of versatile, miniaturized optofluidic ring resonator (OFRR) dye lasers that can be
operated regardless of the refractive index (RI) of the liquid. The OFRR is a piece of a thin-walled fused silica capillary
that integrates the photonic ring resonator with microfluidics. In an OFRR dye laser, the active lasing materials (such as
dye) are passed through the capillary whereas the circular cross section forms a ring resonator and supports whispering
gallery modes (WGMs) that provide optical feedback for lasing. Due to the high Q-factors (> 109), extremely low lasing
threshold can be achieved. The operation wavelength can conveniently be changed by using different dye and fine-tuned
with solvent. The laser can be out-coupled through a fiber taper in touch with the capillary, thus providing an easy
guiding for the laser emission. Our experiments demonstrate lasing through direct excitation and through efficient
energy transfer (ET). Theoretical analysis and experimental results for OFRR lasers are presented.
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.
We present a novel label-free method of quantifying single stranded DNA concentrations in solution using the Liquid
Core Optical Ring Resonator (LCORR). The LCORR is a glass capillary that is capable of evanescent sensing of
analytes while providing fluidic delivery through its hollow core. An evanescent field is excited in the ring-shaped
circumference of the LCORR by externally coupled photons, which circulate via total internal reflection in the form of
Whispering Gallery Modes (WGM's). When the wall of the capillary is etched to under 5 μm, the evanescent field from
the WGM's is exposed in both the internal and external media.
Chemical modification of the interior of the LCORR enables specific capture of target oligonucleotides by hybridization
with a covalently bound probe. Refractive index changes at this interface are shown to produce a measurable change in
the optical signal by shifting the resonance condition of the cavity.
Real time kinetic analysis of the hybridization between the two complimentary strands is demonstrated as well as a
thorough calibration of the sensor response to strand lengths between 25 and 100 bases and bulk concentration from 0.5
nM to 10 μM. Non-specific binding of completely mismatched oligonucleotides is shown to be minimal and single base
mismatch detection is also demonstrated definitively.
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.
In parallel to a stand-alone microsphere resonator and a planar ring resonator on a wafer, the liquid core optical ring
resonator (LCORR) is regarded as the third type of ring resonator that integrates microfluidics with state-of-the-art
photonics. The LCORR employs a micro-sized glass capillary with a wall thickness of a few microns. The circular cross
section of the capillary forms a ring resonator that supports the whispering gallery modes (WGMs), which has the
evanescent field in the core, allowing for repetitive interaction with the analytes carried inside the capillary. Despite the
small physical size of the LCORR and sub-nanoliter sensing volume, the effective interaction length can exceed 10 cm
due to high Q-factor (106), significantly improving the LCORR detection limit. The LCORR is a versatile system that
exhibits excellent fluid handling capability inherent to capillaries and permits non-invasive and quantitative
measurement at any location along the capillary. Furthermore, the LCORR uses the refractive index change as a
transduction signal, which enables label-free detection. Therefore, the LCORR is a promising technology platform for
future sensitive, miniaturized, lab-on-a-chip type sensors. In this paper, we will introduce the concept of the LCORR and
present the theoretical analysis and the experimental results related to the LCORR sensor development.
Label-free optical biosensors offer advantages for many applications due to their simplicity and low cost compared to
fluorescence detection. Thus, it is desirable to develop label-free sensors that can be integrated with advanced
microfluidic systems into dense, multi-purpose biosensor arrays. One candidate technology is ring resonators, which
utilize the resonating whispering gallery modes to create a strongly enhanced optical field in the sensing volume.
Because of the high Q-factor of ring resonators, the optical field can be enhanced by 2-3 orders of magnitude, which
leads to much smaller required light-matter interaction length and sensing volume. These are critical characteristics for
dense integration into lab-on-a-chip systems.
We have developed a novel label-free ring resonator sensor based on a liquid core optical ring resonator (LCORR).
This system uses a glass capillary as both the fluidics and the ring resonator. With the LCORR, we have demonstrated a
measurable whispering gallery mode spectral shift of 30 pm/refractive-index-unit (RIU), which leads to a detection limit
of approximately 10-6 RIU. Additionally, we have achieved an estimated detection limit for protein molecules of 10
pg/mm2. These experimental demonstrations of this novel sensing system will lead to the development of highly
sensitive label-free sensors that are well-suited for dense integration with advanced microfluidics for lab-on-a-chip
Optical ring resonators in the form of a microsphere or microcylinder of a few tens to a few hundreds of μm in diameter represent a new sensing mechanism and have recently drawn increasing attention in bio/chemical sensor development. In a ring resonator, the light circulates along the inner surface in the form of the whispering gallery modes (WGMs) resulting from total internal reflection. Due to the high Q-factor of the WGM, the effective interaction length between the light and the analytes can be 10-100 cm long, despite the sensor's micrometer dimensions. Successful feasibility demonstrations of a single ring resonator sensor have stimulated further investigation on photonic and fluidic integration. In this paper, we present a novel bio/chemical sensor platform based on a liquid core optical ring resonator (LCORR) architecture that takes advantage of the high sensitivity associated with ring resonators and easy sample delivery associated with the hollow core columns. This structure allows for separate engineering of the fluidics and photonics and is well-suited for a 2-D sensor array. The potential result is a micro-sized sensing system capable of detecting multiple agents simultaneously while providing redundancy to reduce false positives. In addition, the sample detection volume can be as low as 100 pL. Here we present an LCORR with a Q-factor of 500,000 (2 pm mode linewidth) and a refractive index sensitivity of 7 nm/RIU. Also, we demonstrate the detection of bovine serum albumin adsorbing to the inner surface as the sample is pumped through the LCORR.