In JoVE (1)

Other Publications (71)

Articles by Xudong Fan in JoVE

Other articles by Xudong Fan on PubMed

Performance Effect in Optical-communication Systems Caused by Phase Ripples of Dispersive Components

Applied Optics. Sep, 2004  |  Pubmed ID: 15468704

We develop a simple theory that relates the performance of an optical component to the variance of the amplitude of its phase ripple that has been weighted by the incoming signal spectrum. Comparisons of model predictions for chirped fiber gratings with 10-Gbit/s test-bed simulations and measurements agree.

Subfemtomole Detection of Small Molecules with Microsphere Sensors

Optics Letters. Dec, 2005  |  Pubmed ID: 16342716

We investigated the feasibility of using a silica microsphere sensor for detection of small molecules. Using the silica molecules (60 Da) at the sphere's surface as a model system, we measured the spectral shifts in the whispering-gallery modes (WGMs) when the sphere size was decreased by a hydrofluoric acid (HF) solution. The results demonstrate that our sensor is capable of detecting a 4 pm (or 0.01 layer of silica) decrease in sphere radius, corresponding to a change of 0.4 fmol silica molecule. These results suggest that small molecules can be detected in trace quantities at the surface of an optical microsphere sensor.

Tuning Whispering Gallery Modes in Optical Microspheres with Chemical Etching

Optics Express. Dec, 2005  |  Pubmed ID: 19503292

We demonstrate a new method to tune the resonance of whispering gallery modes in a fused silica optical microsphere resonator by removing atomic layers from the sphere surface with low concentrations of hydrofluoric acid. Our results show that the WGMs can be tuned over 660 pm (430 GHz), more than one free spectral range of the microsphere resonator, with a tuning precision better than 0.2 pm (130 MHz). Both atomic force microscope images and a Q-factor measurement performed in air suggest that no additional degradation in Q-factor due to surface roughness is introduced during this etching process.

Liquid-core Optical Ring-resonator Sensors

Optics Letters. May, 2006  |  Pubmed ID: 16642098

We have demonstrated a novel sensor architecture based on a liquid-core optical ring-resonator (LCORR) in which a fused silica capillary is utilized to carry the aqueous sample and to act as the ring resonator. The wall thickness of the LCORR is controlled to a few micrometers to expose the whispering gallery mode to the aqueous core. Optical characterization with a water-ethanol mixture shows that the spectral sensitivity of the LCORR sensor is approximately 2.6 nm per refractive index unit. A model based on Mie theory is established to explain the experimental results. The LCORR takes advantage of the high sensitivity, small footprint, and low sample consumption with the ring resonator, as well as the efficient fluidic sample delivery with the capillary, and will open an avenue to future multiplexed sensor array development.

Thermal Characterization of Liquid Core Optical Ring Resonator Sensors

Applied Optics. Jan, 2007  |  Pubmed ID: 17228386

The liquid core optical ring resonator (LCORR) has recently shown promise as a high-sensitivity label-free lab-on-a-chip biological-chemical sensor. We investigate experimentally and theoretically the temperature dependence of the LCORR to establish a noise baseline, which will enable us to implement a temperature stabilization mechanism to reduce the thermally induced noise and to improve the sensor detection limit. Our studies involve analysis of the thermo-optic and thermomechanical effects of fused silica and aluminosilicate glass as they impact LCORR performance. Both thick-walled and thin-walled LCORRs are investigated to elucidate the contribution of water in the core to the thermal response of the LCORRs. Theoretical calculations based on Mie theory are used to verify the experimental observations.

Optical Leaky Waveguide Biosensors for the Detection of Organophosphorus Pesticides

The Analyst. Feb, 2007  |  Pubmed ID: 17260070

Organophosphorus (OP) pesticides can be rapidly detected by integrating organophosphorus hydrolase with an optical leaky waveguide biosensor. This enzyme catalyses the hydrolysis of a wide range of organophosphorus compounds causing an increase in the pH. Thus, the direct detection of OP is possible by monitoring of the pH changes associated with the enzyme's activity. This article describes the use of an optical, leaky waveguide clad with absorbing materials for the detection of OP pesticides by measuring changes in refractive index, absorbance and fluorescence. In the most effective configuration, a thick sensing layer was used to increase the amount of immobilized enzyme and to increase the light interaction with the sensing layer, resulting in a greatly enhanced sensitivity. The platforms developed in this work were successfully used to detect paraoxon and parathion down to 4 nM concentrations.

Integrated Refractive Index Optical Ring Resonator Detector for Capillary Electrophoresis

Analytical Chemistry. Feb, 2007  |  Pubmed ID: 17263318

We developed a novel miniaturized and multiplexed, on-capillary, refractive index (RI) detector using liquid core optical ring resonators (LCORRs) for future development of capillary electrophoresis (CE) devices. The LCORR employs a glass capillary with a diameter of approximately 100 mum and a wall thickness of a few micrometers. The circular cross section of the capillary forms a ring resonator along which the light circulates in the form of the whispering gallery modes (WGMs). The WGM has an evanescent field extending into the capillary core and responds to the RI change due to the analyte conducted in the capillary, thus permitting label-free measurement. The resonating nature of the WGM enables repetitive light-analyte interaction, significantly enhancing the LCORR sensitivity. This LCORR architecture achieves dual use of the capillary as a sensor head and a CE fluidic channel, allowing for integrated, multiplexed, and noninvasive on-capillary detection at any location along the capillary. In this work, we used electro-osmotic flow and glycerol as a model system to demonstrate the fluid transport capability of the LCORRs. In addition, we performed flow speed measurement on the LCORR to demonstrate its flow analysis capability. Finally, using the LCORR's label-free sensing mechanism, we accurately deduced the analyte concentration in real time at a given point on the capillary. A sensitivity of 20 nm/RIU (refractive index units) was observed, leading to an RI detection limit of 10-6 RIU. The LCORR marries photonic technology with microfluidics and enables rapid on-capillary sample analysis and flow profile monitoring. The investigation in this regard will open a door to novel high-throughput CE devices and lab-on-a-chip sensors in the future.

Universal Coupling Between Metal-clad Waveguides and Optical Ring Resonators

Optics Express. Jan, 2007  |  Pubmed ID: 19532287

We demonstrate excitation of whispering gallery modes in optical ring resonators using a gold-clad pedestal planar waveguide structure. The gold-clad structure provides a strong evanescent field for light-coupling into the resonator while enabling low transmission loss throughout much of the visible and near-infrared region. This is advantageous compared to the previously demonstrated anti-resonant reflecting optical waveguide (ARROW) structure, which can only transmit a narrow wavelength band. We show that the height of the pedestal waveguide can be designed to optimize the coupling conditions for the ring resonator. This technology enhances the practicality of optical ring resonators for sensing devices, laser systems, and many other important applications.

Analysis of Biomolecule Detection with Optofluidic Ring Resonator Sensors

Optics Express. Jul, 2007  |  Pubmed ID: 19547254

We theoretically and experimentally analyze the biomolecule detection capability of the liquid core optical ring resonator (LCORR) as a label-free bio/chemical sensor. We first establish a simple and general linear relationship between the LCORR's bulk refractive index sensitivity (BRIS) and its response to molecule deposition onto the surface, which enables us to easily characterize the LCORR sensing performance. Then, biosensing experiments are performed with bovine serum albumin (BSA) and LCORRs of various BRISs. The experimental results are in good agreement with the theoretical prediction. Further analysis shows that the LCORR is capable of detecting BSA below 10 pM with sub-picogram/mm2 mass detection limit.

Opto-fluidic Ring Resonator Lasers Based on Highly Efficient Resonant Energy Transfer

Optics Express. Oct, 2007  |  Pubmed ID: 19550541

We demonstrate an opto-fluidic ring resonator dye laser using highly efficient energy transfer. The active lasing material consists of a donor and acceptor mixture and flows in a fused silica capillary whose circular cross section forms a ring resonator and supports the whispering gallery modes (WGMs) of high Q-factors (>107). The excited states are created in the donor and transferred to the acceptor through the fluorescence resonant energy transfer (FRET), whose emission is coupled into the WGM. Due to the high energy transfer efficiency and high Q-factors, the acceptor exhibits a lasing threshold as low as 0.3 muJ/mm2. We further analyze the energy transfer mechanisms and find that non-radiative Förster transfer is the dominant effect to support the acceptor lasing. FRET lasers using cascade energy transfer and using quantum dots (QDs) as the donor are also presented. Our study will not only lead to development of novel microfluidic lasers with low lasing thresholds and excitation/emission flexibility, but also open an avenue for future laser intra-cavity bio/chemical sensing.

Versatile Opto-fluidic Ring Resonator Lasers with Ultra-low Threshold

Optics Express. Nov, 2007  |  Pubmed ID: 19550838

We develop a versatile integrated opto-fluidic ring resonator (OFRR) dye laser that can be operated regardless of the refractive index (RI) of the liquid. The OFRR is a micro-sized glass capillary with a wall thickness of a few micrometers. When the liquid in the core has an RI lower than that of the capillary wall (n=1.45), the capillary circular cross-section forms the ring resonator and supports the whispering gallery modes (WGMs) that interact evanescently with the gain medium in the core. When the core RI is higher than that of the wall, the WGMs exist at the core/wall interface. In both cases, the WGMs can have extremely high Q-factor (>109), providing excellent optical feedback for low-threshold lasing. In this paper, we analyze the OFRR laser for various core RI's and then we demonstrate the R6G laser when the dye is in ethanol (n=1.36), chloroform (n=1.445), and quinoline (n=1.626). The lasing threshold of 25 nJ/mm(2) is achieved, two to three orders of magnitude lower than the previous work in microfluidic lasers. We further show that the laser emission can be efficiently out-coupled via an optical waveguide in touch with the OFRR for both high and low RI liquid core, allowing for easy guiding and delivery of the laser light.

SERS-based Detection in an Optofluidic Ring Resonator Platform

Optics Express. Dec, 2007  |  Pubmed ID: 19551037

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.

Versatile Waveguide-coupled Optofluidic Devices Based on Liquid Core Optical Ring Resonators

Applied Physics Letters. Dec, 2007  |  Pubmed ID: 21479124

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.

Label-free Quantitative DNA Detection Using the Liquid Core Optical Ring Resonator

Biosensors & Bioelectronics. Feb, 2008  |  Pubmed ID: 18036809

We demonstrated quantitative real-time label-free detection of DNA sequences using the liquid core optical ring resonator (LCORR) sensor. The LCORR is a recently developed sensing platform that integrates microfluidics and photonic sensing technology with low detection limit and sub-nanoliter detection volume. We analyzed experimentally and theoretically the LCORR response to a variety of DNA samples that had different strand lengths (25-100 bases), number of base- mismatches (1-5), and concentrations (10 pM to 10 microM) to evaluate the LCORR sequence detection capability. In particular, we established the linear correlation between the LCORR sensing signal and the molecule density, which allows us to accurately calculate the molecule density on the surface. It is found that the probe surface coverage was 26-51% and the extent of hybridization was 40-50%. The titration curve for 25-base probe and 25-base target DNA yields a dissociation constant of 2.9 nM. With a 37.1 nm/RIU LCORR, detection of 10 pM bulk DNA concentration was demonstrated. The mass detection limit was estimated to be 4 pg/mm(2), corresponding to a density of 10(10) molecules/cm(2) on the surface. We also showed that the LCORR was sensitive enough to differentiate DNA with only a few base-mismatches based on the raw sensing signal and kinetic analysis. Our work will provide important insight into the light-DNA interaction at the ring resonator surface and lay a foundation for future LCORR-based DNA label-free microarray development.

On-column Micro Gas Chromatography Detection with Capillary-based Optical Ring Resonators

Analytical Chemistry. Mar, 2008  |  Pubmed ID: 18271605

We developed a novel on-column micro gas chromatography (microGC) detector using capillary based optical ring resonators (CBORRs). The CBORR is a thin-walled fused silica capillary with an inner diameter ranging from a few tens to a few hundreds of micrometers. The interior surface of the CBORR is coated with a layer of stationary phase for gas separation. The circular cross section of the CBORR forms a ring resonator and supports whispering gallery modes (WGMs) that circulate along the ring resonator circumference hundreds of times. The evanescent field extends into the core and is sensitive to the refractive index change induced by the interaction between the gas sample and the stationary phase. The WGM can be excited and monitored at any location along the CBORR by placing a tapered optical fiber against the CBORR, thus enabling on-column real-time detection. Rapid separation of both polar and nonpolar samples was demonstrated with subsecond detection speed. Theoretical work was also established to explain the CBORR detection mechanism. While low-nanogram detection limits are observed in these preliminary tests, many methods for improvements are under investigation. The CBORR is directly compatible with traditional capillary GC columns without any dead volumes. Therefore, the CBORR-based muGC is a very promising technology platform for rapid, sensitive, and portable analytical devices.

Opto-fluidic Micro-ring Resonator for Sensitive Label-free Viral Detection

The Analyst. Mar, 2008  |  Pubmed ID: 18299750

We have demonstrated sensitive label-free virus detection using the opto-fluidic ring resonator (OFRR) sensor. The OFRR is a novel sensing platform that integrates the microfluidics and photonic sensing technology with a low detection limit and small volume. In our experiment, filamentous bacteriophage M13 was used as a safe model system. Virus samples were flowed through the OFRR whose surface was coated with M13-specific antibodies. We studied the sensor performance by monitoring in real-time the virus and antibody interaction. It is shown that OFRR can detect M13 with high specificity and sensitivity. The detection limit is approximately 2.3 x 10(3) pfu mL(-1) and the detection dynamic range spanned seven orders of magnitude. Theoretical analysis was also carried out to confirm the experimental results. Our study will lead to development of novel OFRR-based, sensitive, rapid, and low-cost micro total analysis devices for virus detection.

Rapid Chemical-vapor Sensing Using Optofluidic Ring Resonators

Optics Letters. Apr, 2008  |  Pubmed ID: 18414533

We develop rapid chemical-vapor sensors based on optofluidic ring resonators (OFRRs). The OFRR is a glass capillary whose circular wall supports the circulating waveguide modes (WGMs). The OFRR inner surface is coated with a vapor-sensitive polymer. The analyte and polymer interaction causes the polymer refractive index to change, which is detected as a WGM spectral shift. Owing to the excellent fluidics, the OFRR exhibits subsecond detection and recovery time with a flow rate of only 1 mL/min, a few orders of magnitude lower than that in the existing optical vapor sensors. The detection limit is estimated to be 5.6 x 10(-6) refractive index units, over ten times better than other ring-resonator vapor sensors. Ethanol and hexane vapors are used as a model system, and chemical differentiation is demonstrated with different polymer coatings.

On the Performance Quantification of Resonant Refractive Index Sensors

Optics Express. Jan, 2008  |  Pubmed ID: 18542175

Refractive index (RI) sensors based on optical resonance techniques are receiving a high degree of attention because of the need to develop simple, low-cost, high-throughput detection technologies for a number of applications. While the sensing mechanism of most of the reported RI sensors is similar, the construction is quite different from technique to technique. It is desirable to have a uniform mechanism for comparing the various RI sensing techniques, but to date there exists a degree of variation as to how the sensing performance is quantified. Here we set forth a rigorous definition for the detection limit of resonant RI sensors that accounts for all parameters that affect the detection performance. Our work will enable a standard approach for quantifying and comparing the performance of optical resonance-based RI sensors. Additionally, it will lead to design strategies for performance improvement of RI sensors.

Phage-based Label-free Biomolecule Detection in an Opto-fluidic Ring Resonator

Biosensors & Bioelectronics. Nov, 2008  |  Pubmed ID: 18550355

We have developed a sensitive and inexpensive opto-fluidic ring resonator (OFRR) biosensor using phage as a receptor for analyte detection. Phages have distinct advantages over antibodies as biosensor receptors. First, affinity selection from large libraries of random peptides displayed on phage provides a generic method of discovering receptors for detecting a wide range of analytes with high specificity and sensitivity. Second, phage production can be less complicated and less expensive than antibody production. Third, phages withstand harsh environments, reducing the environmental limitations and enabling regeneration of the biosensor surface. In this work, filamentous phage R5C2, displaying peptides that bind streptavidin specifically, was employed as a model receptor to demonstrate the feasibility of a phage-based OFRR biosensor. The experimental detection limit was approximately 100pM streptavidin and the K(d(apparent)) is 25pM. Specificity was verified using the RAP 5 phage, which is not specific to streptavidin, as the negative control. Sensing surface regeneration results show that the phage maintained functionality after surface regeneration, which greatly improves the sensors' reusability. The phage-based OFRR biosensor will become a promising platform for universal biomolecule detection with high sensitivity, low cost, and good reusability.

Sensitive Optical Biosensors for Unlabeled Targets: a Review

Analytica Chimica Acta. Jul, 2008  |  Pubmed ID: 18558119

This article reviews the recent progress in optical biosensors that use the label-free detection protocol, in which biomolecules are unlabeled or unmodified, and are detected in their natural forms. In particular, it will focus on the optical biosensors that utilize the refractive index change as the sensing transduction signal. Various optical label-free biosensing platforms will be introduced, including, but not limited to, surface plasmon resonance, interferometers, waveguides, fiber gratings, ring resonators, and photonic crystals. Emphasis will be given to the description of optical structures and their respective sensing mechanisms. Examples of detecting various types of biomolecules will be presented. Wherever possible, the sensing performance of each optical structure will be evaluated and compared in terms of sensitivity and detection limit.

PDMS Embedded Opto-fluidic Microring Resonator Lasers

Optics Express. Jul, 2008  |  Pubmed ID: 18607433

Opto-fluidic ring resonator (OFRR) dye lasers are embedded in low index polydimethylsiloxane (PDMS) to achieve enhanced portability, mechanical stability, and potential integration with conventional soft lithography based microfluidics for development of micro total analysis systems. The OFRR retains high Q-factors (> 10(6)) and exhibits low lasing threshold (<1 microJ/mm(2)). Fiber prisms and tapered optical fibers are used to directionally couple out the laser emission. At 2.2 microJ/mm(2) pump intensity, the laser output from the fiber prism is 80 nW, corresponding to 50% power extraction efficiency. A microarray structure of parallel OFRRs is also demonstrated, allowing simultaneous multi-color emissions.

Analysis of Ring Resonators for Chemical Vapor Sensor Development

Optics Express. Jul, 2008  |  Pubmed ID: 18607434

We carry out simulations based on a four-layer Mie model to systematically analyze the sensing performance of ring resonator chemical vapor sensors. Two sensor configurations are investigated, in which a polymer layer is coated on either interior or exterior surface of a fused silica cylindrical ring resonator. Upon the interaction of the polymer and the vapor analyte, the refractive index (RI) and the thickness of the polymer layer change, leading to a spectral shift in the resonant modes that are supported by the ring resonator. The RI sensitivity and thickness sensitivity are studied as a function of the polymer coating thickness and RI, the ring resonator size and wall thickness, and resonant mode order and polarization. Similarities and differences between the two sensor configurations are also discussed. Our work should provide a general guidance in development of sensitive ring resonator chemical vapor sensors.

Label-free Detection with the Resonant Mirror Biosensor

Methods in Molecular Biology (Clifton, N.J.). 2009  |  Pubmed ID: 19151938

The resonant mirror (RM) biosensor is a leaky waveguide-based instrument that uses the evanescent field to probe changes in the refractive index at the sensing surface.The RM can therefore be used to monitor in real-time and label-free the interaction between an analyte in solution and its biospecific partner immobilized on the waveguide surface.The RM has been used in studying the interaction of a variety of moieties including proteins, carbohydrates, cells, nucleic acids and receptors, leading to applications in areas such as clinical diagnostics, homeland security, and pharmaceutical and biomolecular interactions. This chapter will review the principle of this biosensor, and the recent advances in instrumentation, different immobilization chemistries, and kinetic studies, as well as some applications.

Label-free Detection with the Liquid Core Optical Ring Resonator Sensing Platform

Methods in Molecular Biology (Clifton, N.J.). 2009  |  Pubmed ID: 19151939

Optical label-free detection prevents the cost and complexity of fluorescence and radio labeling while providing accurate quantitative and kinetic results. We have developed a new optical label-free sensor called the liquid core optical ring resonator (LCORR). The LCORR integrates optical ring resonator sensors into the microfluidic delivery system by using glass capillaries with a thin wall. The LCORR is capable of performing refractive index detection on liquid samples, as well as bio/chemical analyte detection down to detection limits on the scale of pg/mm2 on a sensing surface.

Highly Versatile Fiber-based Optical Fabry-Pérot Gas Sensor

Optics Express. Feb, 2009  |  Pubmed ID: 19219178

We develop a versatile, compact, and sensitive fiber-based optical Fabry-Pérot (FP) gas sensor. The sensor probe is composed of a silver layer and a vapor-sensitive polymer layer that are sequentially deposited on the cleaved fiber endface, thus forming an FP cavity. The interference spectrum resulting from the reflected light at the silver-polymer and polymer-air interfaces changes when the polymer is exposed to gas analytes. This structure enables using any polymer regardless of the polymer refractive index (RI), which significantly enhances the sensor versatility. In experiments, we use polyethylene glycol (PEG) 400 (RI=1.465-1.469) and Norland Optical Adhesive (NOA) 81 (RI=1.53-1.56) as the gas sensing polymer and show drastically different sensor response to hexanol, methanol, and acetone. The estimated sensitivity for methanol vapor is 3.5 pm/ppm and 0.1 pm/ppm for PEG 400 and NOA 81, respectively, with a detection limit on the order of 1-10 ppm. Gas sensing for the analytes delivered in both continuous flow mode and pulsed mode is demonstrated.

Robust Integrated Optofluidic-ring-resonator Dye Lasers

Optics Letters. Apr, 2009  |  Pubmed ID: 19340213

We demonstrate a robust optofluidic dye laser that integrates fluidics with a high Q-factor ring resonator. In this optofluidic laser the ring resonator is formed by an optical fiber fused on the inner surface of a glass capillary serving as a fluidic channel. Laser oscillation is achieved with a threshold of 7 microJ/mm2 per pulse. Furthermore, the laser emission can be directionally outcoupled through a fiber prism for easy and efficient light delivery.

Optofluidic Ring Resonator Sensors for Rapid DNT Vapor Detection

The Analyst. Jul, 2009  |  Pubmed ID: 19562206

We demonstrated rapid 2,4-dinitrotoluene (DNT) vapor detection at room temperature based on an optofluidic ring resonator (OFRR) sensor. With the unique on-column separation and detection features of OFRR vapor sensors, DNT can be identified from other interferences coexisting in the analyte sample mixture, which is especially useful in the detection of explosives from practical complicated vapor samples usually containing more volatile analytes. The DNT detection limit is approximately 200 pg, which corresponds to a solid phase microextraction (SPME) sampling time of only 1 second at room temperature from equilibrium headspace. A theoretical analysis was also performed to account for the experimental results. Our study shows that the OFRR vapor sensor is a promising platform for the development of a rapid, low-cost, and portable analytical device for explosive detection and monitoring.

Compact Quantum Dot Probes for Rapid and Sensitive DNA Detection Using Highly Efficient Fluorescence Resonant Energy Transfer

Nanotechnology. Jul, 2009  |  Pubmed ID: 19581695

We developed a simple method for quickly synthesizing compact quantum dot (QD)-DNA probes for sensitive DNA detection using fluorescence resonant energy transfer (FRET). The density of DNA probes on the QD surface was controlled to avoid steric hindrance and to promote rapid hybridization with target DNA molecules. The radius of the final QDs was only around 3 nm after applying the functional coating, enabling highly efficient energy transfer. It was demonstrated that nearly 70% transfer efficiency could be achieved with only a few DNA molecules on each QD and that the FRET-based DNA detection could be carried out within 10 min with a sub-nM detection limit. Theoretical analysis was also performed to confirm our results.

Rapid and Label-free Detection of Breast Cancer Biomarker CA15-3 in Clinical Human Serum Samples with Optofluidic Ring Resonator Sensors

Analytical Chemistry. Dec, 2009  |  Pubmed ID: 19911811

Sensitive and specific detection of breast cancer biomarker CA15-3 in human serum is an important step toward successful evaluation of clinical treatment and prediction of breast cancer recurrence. In this work, we developed an optofluidic ring resonator (OFRR) sensor and the corresponding sensing protocols for label-free CA15-3 detection without any additional signal amplification steps. Nonspecific serum protein adsorption was minimized with effective surface blocking methods. The sensor performance for CA15-3 detection was first characterized in phosphate-buffered saline (PBS) buffer and in fetal calf serum. Then the potential use of the OFRR as a simple clinical laboratory testing device for breast cancer diagnostics was tested by measuring the CA15-3 level in clinical human serum samples, and the results were compared with those of standard clinical lab tests. It was found that the OFRR was capable of detecting approximately 1 unit/mL CA15-3 in both PBS buffer and diluted serum within approximately 30 min. Our work marks the first demonstration of the optical ring resonator biosensor in real clinical applications that features low cost, simple detection procedures, rapid response time, low sample consumption, and high specificity.

Label-free Analysis of DNA Methylation Using Optofluidic Ring Resonators

Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference. 2009  |  Pubmed ID: 19964593

We demonstrate the utility of the opto-fluidic ring resonator (OFRR) sensor for analyzing methylated oligonucleotides. Cytosine methylation, a regular epigenetic function in cellular growth and metabolism, may have ties to abnormal suppression of key genes involved with cellular proliferation. Such behavior is suspected to be strongly related to the occurrence of several types of cancers. The OFRR is demonstrated as a tool both for detecting DNA hybridization and methylated cytosines residues.

Overview of the Optofluidic Ring Resonator: a Versatile Platform for Label-free Biological and Chemical Sensing

Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference. 2009  |  Pubmed ID: 19965134

Highly sensitive detection of biological and chemical analytes has significant importance within medical science, environmental monitoring, food quality, national security and defense. The opto-fluidic ring resonator (OFRR) is a relatively new solution for label-free optical sensing that is compatible with a versatile range of analytes. A capillary-based platform, the OFRR supports whispering gallery modes within its circular cross-section and conducts evanescent sensing within its hollow core. Herein, we provide an overview of the basic operation principles of the OFRR and some examples of its most important applications, including the detection of proteins, virus, DNA molecules, whole cells, vapors and pesticides.

Rapid Tandem-column Micro-gas Chromatography Based on Optofluidic Ring Resonators with Multi-point On-column Detection

The Analyst. Jan, 2010  |  Pubmed ID: 20024197

We demonstrated a novel tandem-column micro-gas chromatography (microGC) based on optofluidic ring resonator (OFRR). The OFRR is a thin-walled fused silica capillary whose interior surface is coated with a polymeric stationary phase. The circular cross section of the OFRR forms the micro-ring resonator and supports whispering gallery modes (WGMs). Via tapered optical fibers in contact with the OFRR, the WGM can be excited externally at any positions along the OFRR capillary, thus enabling multi-point, on-column, real-time detection of vapor molecules flowing through the OFRR. In the present OFRR-based tandem-column-based microGC implementation, a 180 cm long conventional GC column coated with a nonpolar stationary phase was followed by a relatively short OFRR column coated with a polar phase. Two detection positions, one at the inlet of the OFRR and the other a few centimeters downstream, were used to monitor the separation achieved by the first and the second column, respectively. Owing to the multi-point on-column detection that provides complementary retention time information on each chemical compound, co-eluted analytes can be well separated and identified on at least one detection channel and no modulation is needed at the interface of tandem columns. Separation and detection of twelve analytes with various volatilities and polarities within four minutes were demonstrated. In addition, the chromatograms obtained from three different locations along the OFRR column demonstrated the system's capability of on-column monitoring of the separation process for the target analyte in a vapor mixture. Our results will lead to the development of a rapid, simple, and portable microGC system with significantly improved selectivity and chemical identification capabilities.

Fabry-Pérot Cavity Sensors for Multipoint On-column Micro Gas Chromatography Detection

Analytical Chemistry. Jun, 2010  |  Pubmed ID: 20441156

We developed and characterized a Fabry-Pérot (FP) sensor module based micro gas chromatography (microGC) detector for multipoint on-column detection. The FP sensor was fabricated by depositing a thin layer of metal and a layer of gas-sensitive polymer consecutively on the endface of an optical fiber, which formed the FP cavity. Light partially reflected from the metal layer and the polymer-air interface generated an interference spectrum, which shifted as the polymer layer absorbed the gas analyte. The FP sensor module was then assembled by inserting the FP sensor into a hole drilled in the wall of a fused-silica capillary, which can be easily connected to the conventional gas chromatography (GC) column through a universal quick seal column connector, thus enabling on-column real-time detection. We characterized the FP sensor module based microGC detector. Sensitive detection of various gas analytes was achieved with subnanogram detection limits. The rapid separation capability of the FP sensor module assembled with both single- and tandem-column systems was demonstrated, in which gas analytes having a wide range of polarities and volatilities were well-resolved. The tandem-column system obtained increased sensitivity and selectivity by employing two FP sensor modules coated with different polymers, showing great system versatility.

Nanofibers and Nanoparticles from the Insect-capturing Adhesive of the Sundew (Drosera) for Cell Attachment

Journal of Nanobiotechnology. 2010  |  Pubmed ID: 20718990

The search for naturally occurring nanocomposites with diverse properties for tissue engineering has been a major interest for biomaterial research. In this study, we investigated a nanofiber and nanoparticle based nanocomposite secreted from an insect-capturing plant, the Sundew, for cell attachment. The adhesive nanocomposite has demonstrated high biocompatibility and is ready to be used with minimal preparation.

Bioinspired Optofluidic FRET Lasers Via DNA Scaffolds

Proceedings of the National Academy of Sciences of the United States of America. Sep, 2010  |  Pubmed ID: 20798062

Optofluidic dye lasers hold great promise for adaptive photonic devices, compact and wavelength-tunable light sources, and micro total analysis systems. To date, however, nearly all those lasers are directly excited by tuning the pump laser into the gain medium absorption band. Here we demonstrate bioinspired optofluidic dye lasers excited by FRET, in which the donor-acceptor distance, ratio, and spatial configuration can be precisely controlled by DNA scaffolds. The characteristics of the FRET lasers such as spectrum, threshold, and energy conversion efficiency are reported. Through DNA scaffolds, nearly 100% energy transfer can be maintained regardless of the donor and acceptor concentration. As a result, efficient FRET lasing is achieved at an unusually low acceptor concentration of micromolar, over 1,000 times lower than that in conventional optofluidic dye lasers. The lasing threshold is on the order of μJ/mm(2). Various DNA scaffold FRET lasers are demonstrated to illustrate vast possibilities in optofluidic laser designs. Our work opens a door to many researches and applications such as intracavity bio/chemical sensing, biocontrolled photonic devices, and biophysics.

Demonstration of the Coupling of Optofluidic Ring Resonator Lasers with Liquid Waveguides

Optics Letters. Sep, 2010  |  Pubmed ID: 20808395

Optofluidic lasers are of particular interest for lab-on-a-chip-type devices, with broad spectral tunability, convenient microfluidic integration, and a small footprint. Optofluidic ring resonator (OFRR) lasers are advantageous in terms of size but typically generate nondirectional emission that is of minimal practical use. We introduce two unique geometries for soft-lithography-based OFRR lasers--side-coupled rings and spiral rings--both of which can be produced in polydimethyl siloxane substrates with contact molding. These rings utilize evanescent and direct butt-coupling, respectively, to effectively couple the OFRR laser emission into microfluidic channels. A laser threshold of a few to tens of microJ/mm(2) is achieved.

Label-free DNA Methylation Analysis Using Opto-fluidic Ring Resonators

Biosensors & Bioelectronics. Nov, 2010  |  Pubmed ID: 20846848

The opto-fluidic ring resonator (OFRR) is a sensitive label-free optical biosensor that is uniquely well suited for photonic and fluidic integration. For the first time we have explored the utility of this novel instrument for the analysis of methylation in oligonucleotides using the MBD-2 (methyl binding) protein as the capture molecule. This application has strong relevance to cancer research and future clinical tools through the study of methylation patterns in important gene promoters. In this work we quantitatively characterized the OFRR's response to artificially methylated ssDNA and dsDNA as a function of the number of methylated cytosines and DNA concentration. The effect of hemi- versus fully methylated oligonucleotides was also investigated. Additionally, anti 5-methylcytidine antibody was also used as the capture molecule and compared with MBD-2. It is found that the antibody has stronger affinity for ssDNA, whereas MBD-2 is much better at binding dsDNA.

Highly Sensitive Multiplexed Heavy Metal Detection Using Quantum-dot-labeled DNAzymes

ACS Nano. Oct, 2010  |  Pubmed ID: 20925347

We developed highly sensitive and specific nanosensors based on quantum dots (QDs) and DNAzyme for multiplexed detection of heavy metal ions in liquid. The QDs were coated with a thin silica layer for increased stability and higher quantum yield while maintaining a relatively small size for highly efficient energy transfer. The QD-DNAzyme nanosensors were constructed by conjugating quencher-labeled DNAzymes onto the surface of carboxyl-silanized QDs. In the presence of metal ions, the emission is restored due to the cleavage of DNAzymes. The detection could be completed within 25 min with a single laser excitation source. The detection limit of 0.2 and 0.5 nM was experimentally achieved for Pb(2+) and Cu(2+), respectively, which is a 50- and 70-fold improvement over the recent results obtained with dye molecules. Multiplexed detection was also demonstrated using two different colors of QDs, showing negligible cross-talk between the Pb(2+) detection and Cu(2+) detection.

Analysis of Single Nanoparticle Detection by Using 3-dimensionally Confined Optofluidic Ring Resonators

Optics Express. Nov, 2010  |  Pubmed ID: 21164854

We theoretically analyze the ability of 3-dimensionally confined optofluidic ring resonators (OFRRs) for detection of a single nanoparticle in water and in air. The OFRR is based on a glass capillary, on which bottle-shaped and bubble-shaped ring resonators can form. The spectral position of the whispering gallery mode in the OFRR shifts when a nanoparticle is attached to the OFRR inner surface. For both ring resonator structures, the electric field at the inner surface can be optimized by choosing the right wall thickness. Meanwhile, different electric field confinement along the capillary longitudinal axis can be achieved with different curvatures. Both effects significantly increase the sensitivity of the ring resonator for single nanoparticle detection. It is found that the sensitivity is enhanced about 10 times, as compared to that of a solid microsphere biosensor recently reported, and that the smallest detectable nanoparticle is estimated to be less than 20 nm in radius for a Δλ/λ resolution of 10(-8). The high sensitivity and the naturally integrated capillary based microfluidics make the OFRR a very promising sensing platform for detection of various nano-sized bio/chemical species in liquid as well as in air.

Label Free Detection of CD4+ and CD8+ T Cells Using the Optofluidic Ring Resonator

Sensors (Basel, Switzerland). 2010  |  Pubmed ID: 22219687

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.

Optical Ring Resonators for Biochemical and Chemical Sensing

Analytical and Bioanalytical Chemistry. Jan, 2011  |  Pubmed ID: 20938769

In the past few years optical ring resonators have emerged as a new sensing technology for highly sensitive detection of analytes in liquid or gas. This article introduces the ring resonator sensing principle, describes various ring resonator sensor designs, reviews the current state of the field, and presents an outlook of possible applications and related research and development directions.

Robust Silica-coated Quantum Dot-molecular Beacon for Highly Sensitive DNA Detection

Biosensors & Bioelectronics. Mar, 2011  |  Pubmed ID: 21458980

We synthesized and characterized small yet highly robust silica-coated quantum dots (QDs) and then used them to develop highly sensitive molecular beacon (MB) for DNA detection. As compared to the previously reported methods, our silica coating approach enabled simple and rapid synthesis of silica-coated QDs in large quantities and high concentrations with a well-controlled silica layer. The QDs such made were stable and had a high quantum yield in a wide range of pH values (1-14) and high salt concentrations (up to 2M). They were less than 10nm in diameter, much smaller than current silica-coated QDs, thus allowing for efficient energy transfer. The MB sensor based on these silica-coated QDs was capable of rapidly detecting the target DNA at 0.1nM concentration within 15min. It could also differentiate the target DNA from the single base mismatched DNA. The QD-MB developed in this work can be used for highly sensitive and selective detection of DNA and other biomolecules in homogeneous solution and inside a cell, as well as in harsh environment.

Rapid, Sensitive DNT Vapor Detection with UV-assisted Photo-chemically Synthesized Gold Nanoparticle SERS Substrates

The Analyst. Jul, 2011  |  Pubmed ID: 21594246

We report rapid, sensitive, and direct detection of 2,4-dinitrotoluene (DNT) vapor using tailored gold nanoparticles (Au-NPs) as the SERS substrate. The Au-NPs were synthesized using the UV-assisted photo-chemical reduction method and subsequently formed a monolayer on the glass slide through polymer-mediated self-assembly. The SERS substrate such prepared has high SERS enhancement, high affinity towards DNT vapor, and rapid response to the DNT adsorption/desorption. We systematically studied the effect of the Au-NP size and surface density on the SERS performance such as enhancement factor and response time. With the optimized SERS substrate, an enhancement factor over 5.6 × 10(6) was achieved. Furthermore, real-time detection of DNT vapor with only 0.35 second data acquisition time was demonstrated using a 12 mW laser. Compared to previously reported results, we achieved two orders of magnitude reduction in detection time and more than one order of magnitude reduction in excitation laser power. The detection limit is estimated to be 0.4 attogram, which corresponds to a sub-ppb DNT concentration in air. This work will lead to the development of ultra-fast and ultra-sensitive SERS devices for explosive identification and monitoring.

Demonstration of Motionless Knudsen Pump Based Micro-gas Chromatography Featuring Micro-fabricated Columns and On-column Detectors

Lab on a Chip. Oct, 2011  |  Pubmed ID: 21869988

This paper reports the investigation of a micro-gas chromatography (μGC) system that utilizes an array of miniaturized motionless Knudsen pumps (KPs) as well as microfabricated separation columns and optical detectors. A prototype system was built to achieve a flow rate of 1 mL min(-1) and 0.26 mL min(-1) for helium and dry air, respectively, when they were used as carrier gas. This system was then employed to evaluate GC performance compromises and demonstrate the ability to separate and detect gas mixtures containing analytes of different volatilities and polarities. Furthermore, the use of pressure programming of the KP array was demonstrated to significantly shorten the analysis time while maintaining a high detection resolution. Using this method, we obtained a high resolution detection of 5 alkanes of different volatilities within 5 min. Finally, we successfully detected gas mixtures of various polarities using a tandem-column μGC configuration by installing two on-column optical detectors to obtain complementary chromatograms.

Versatile Optofluidic Ring Resonator Lasers Based on Microdroplets

Optics Express. Sep, 2011  |  Pubmed ID: 21996908

We develop a novel nL-sized microdroplet laser based on the capillary optofluidic ring resonator (OFRR). The microdroplet is generated in a microfluidic channel using two immiscible fluids and is subsequently delivered to the capillary OFRR downstream. Despite the presence of the high refractive index (RI) carrier fluid, the lasing emission can still be achieved for the droplet formed by low RI solution. The lasing threshold of 1.54 µJ/mm(2) is achieved, >6 times lower than the state-of-the-art, thanks to the high Q-factor of the OFRR. Furthermore, the lasing emission can be conveniently coupled into an optical fiber. Finally, tuning of the lasing wavelength is achieved via highly efficient fluorescence resonance energy transfer processes by merging two different dye droplets in the microfluidic channel. Versatility combined with improved lasing characteristics makes our OFRR droplet laser an attractive platform for high performance optofluidic lasers and bio/chemical sensing with small sample volumes.

Microfabricated Optofluidic Ring Resonator Structures

Applied Physics Letters. Oct, 2011  |  Pubmed ID: 22053110

We describe the fabrication and preliminary optical characterization of rugged, Si-micromachined optofluidic ring resonator (μOFRR) structures consisting of thin-walled SiO(x) cylinders with expanded midsections designed to enhance the three-dimensional confinement of whispering gallery modes (WGMs). These μOFRR structures were grown thermally at wafer scale on the interior of Si molds defined by deep-reactive-ion etching and pre-treated to reduce surface roughness. Devices 85-μm tall with 2-μm thick walls and inner diameters ranging from 50 to 200 μm supported pure-mode WGMs with Q-factors >10(4) near 985 nm. Advantages for eventual vapor detection in gas chromatographic microsystems are highlighted.

Optofluidic Microsystems for Chemical and Biological Analysis

Nature Photonics. Oct, 2011  |  Pubmed ID: 22059090

Optofluidics - the synergistic integration of photonics and microfluidics - has recently emerged as a new analytical field that provides a number of unique characteristics for enhanced sensing performance and simplification of microsystems. In this review, we describe various optofluidic architectures developed in the past five years, emphasize the mechanisms by which optofluidics enhances bio/chemical analysis capabilities, including sensing and the precise control of biological micro/nanoparticles, and envision new research directions to which optofluidics leads.

Ultrasensitive Optofluidic Surface-enhanced Raman Scattering Detection with Flow-through Multihole Capillaries

ACS Nano. Jan, 2012  |  Pubmed ID: 22176766

3-Dimensional surface-enhanced Raman scattering (SERS) detection integrated with optofluidics offers many advantages over conventional SERS conducted under planar and static conditions. In this paper, we developed a novel optofluidic SERS platform based on nanoparticle-functionalized flow-through multihole capillaries for rapid, reliable, and ultrasensitive analyte detection. The unique configuration not only provides 3-dimensional geometry for significantly increased SERS-active area and inherent fluidic channels for rapid and efficient sample delivery, but also confines and transmits light along the capillary for large SERS signal accumulation. Using a capillary consisting of thousands of micrometer-sized holes adsorbed with gold nanoparticles, we investigated the proposed optofluidic SERS system using the transverse and longitudinal detection methods, where the SERS excitation and collection were perpendicular to and along the capillary, respectively. A detection limit better than 100 fM for rhodamine 6G was achieved with an enhancement factor exceeding 10(8).

Distinguishing DNA by Analog-to-digital-like Conversion by Using Optofluidic Lasers

Angewandte Chemie (International Ed. in English). Jan, 2012  |  Pubmed ID: 22213205

Rapid, Sensitive, and Multiplexed On-chip Optical Sensors for Micro-gas Chromatography

Lab on a Chip. Feb, 2012  |  Pubmed ID: 22245960

We developed and characterized a rapid, sensitive and integrated optical vapor sensor array for micro-gas chromatography (μGC) applications. The sensor is based on the Fabry-Pérot (FP) interferometer formed by a micrometre-thin vapor-sensitive polymer layer coated on a silicon wafer. The thickness and the refractive index of the polymer vary in response to the vapor analyte, resulting in a change in the reflected intensity of the laser impinged on the sensor. In our study, four different polymers were coated on four wells pre-etched on a silicon wafer to form a spatially separated sensor array. A CMOS imager was employed to simultaneously monitor the polymers' response, thus enabling multiplexed detection of a vapor analyte passing through the GC column. A sub-second detection time was demonstrated. In addition, a sub-picogram detection limit was achieved, representing orders of magnitude improvement over the on-chip vapor sensors previously reported.

Self-referenced Composite Fabry-Pérot Cavity Vapor Sensors

Optics Express. Jan, 2012  |  Pubmed ID: 22274444

We develop a versatile, self-referenced composite Fabry-Pérot (FP) sensor and the corresponding detection scheme for rapid and precise measurement of vapors. The composite FP vapor sensor is formed by etching two juxtaposed micron-deep wells, with a precisely controlled offset in depth, on a silicon wafer. The wells are then coated with a vapor sensitive polymer and the reflected light from each well is detected by a CMOS imager. Due to its self-referenced nature, the composite FP sensor is able to extract the change in thickness and refractive index of the polymer layer upon exposure to analyte vapors, thus allowing for accurate vapor quantitation regardless of the polymer thickness, refractive index, and light incident angle and wavelength. Theoretical analysis is first performed to elucidate the underlying detection principle, followed by experimental demonstration at two different incident angles showing rapid and consistent measurement of the polymer changes when the polymer is exposed to three different analytes at various concentrations. The vapor detection limit is found to be on the order of a few pico-grams (~100 ppb).

Ultrasensitive Vapor Detection with Surface-enhanced Raman Scattering-active Gold Nanoparticle Immobilized Flow-through Multihole Capillaries

Analytical Chemistry. Apr, 2012  |  Pubmed ID: 22413933

We developed novel flow-through surface-enhanced Raman scattering (SERS) platforms using gold nanoparticle (Au-NP) immobilized multihole capillaries for rapid and sensitive vapor detection. The multihole capillaries consisting of thousands of micrometer-sized flow-through channels provide many unique characteristics for vapor detection. Most importantly, its three-dimensional SERS-active micro-/nanostructures make available multilayered assembly of Au-NPs, which greatly increase SERS-active surface area within a focal volume of excitation and collection, thus improving the detection sensitivity. In addition, the multihole capillary's inherent longitudinal channels offer rapid and convenient vapor delivery, yet its micrometer-sized holes increase the interaction between vapor molecules and SERS-active substrate. Experimentally, rapid pyridine vapor detection (within 1 s of exposure) and ultrasensitive 4-nitrophenol vapor detection (at a sub-ppb level) were successfully achieved in open air at room temperature. Such an ultrasensitive SERS platform enabled, for the first time, the investigation of both pyridine and 4-nitrophenol vapor adsorption isotherms at very low concentrations. Type I and type V behaviors of the International Union of Pure and Applied Chemistry isotherm were well observed, respectively.

Detection of Escherichia Coli O157:H7 and Salmonella in Ground Beef by a Bead-free Quantum Dot-facilitated Isolation Method

International Journal of Food Microbiology. May, 2012  |  Pubmed ID: 22445913

The aims of this study were to introduce a new immunological bead-free cell detection method using quantum dots (QDs) as reporter markers for foodborne pathogen detection. QDs are nanosized particles with long-term photostability, high quantum yield, broad absorption spectra, and narrow, symmetric emission and high signal-to-noise ratio. The chemical compound [(1-ethyl-3-3-dimethylaminopropyl) carbodiimide hydrochloride] (EDC) and protein A were used as crosslinkers for manufacturing QD-antibody conjugates. To minimize the inhibition of QD fluorescence by the magnetic beads, the beads were removed after the primary pathogen isolation and before fluorescence measurement. Detection signals were increased four-fold after employing the bead-free isolation method. With a 24-h enrichment, the bead-free QD-facilitated detection method was able to detect 10 CFU/g Escherichia coli O157:H7 and Salmonella from artificially contaminated ground beef. To our knowledge, this detection method is the first research that combined a new EDC-protein A QD-labeling technique and bead-free fluorescence measurement to detect E. coli O157:H7 and Salmonella in ground beef.

Adaptive Two-dimensional Microgas Chromatography

Analytical Chemistry. May, 2012  |  Pubmed ID: 22468727

We proposed and investigated a novel adaptive two-dimensional (2-D) microgas chromatography system, which consists of one 1st-dimensional column, multiple parallel 2nd-dimensional columns, and a decision-making module. The decision-making module, installed between the 1st- and 2nd-dimensional columns, normally comprises an on-column nondestructive vapor detector, a flow routing system, and a computer that monitors the detection signal from the detector and sends out the trigger signal to the flow routing system. During the operation, effluents from the 1st-dimensional column are first detected by the detector and, then, depending on the signal generated by the detector, routed to one of the 2nd-dimensional columns sequentially for further separation. As compared to conventional 2-D GC systems, the proposed adaptive GC scheme has a number of unique and advantageous features. First and foremost, the multiple parallel columns are independent of each other. Therefore, their length, stationary phase, flow rate, and temperature can be optimized for best separation and maximal versatility. In addition, the adaptive GC significantly lowers the thermal modulator modulation frequency and hence power consumption. Finally, it greatly simplifies the postdata analysis process required to reconstruct the 2-D chromatogram. In this paper, the underlying working principle and data analysis of the adaptive GC was first discussed. Then, separation of a mixture of 20 analytes with various volatilities and polarities was demonstrated using an adaptive GC system with a single 2nd-dimensional column. Finally, an adaptive GC system with dual 2nd-dimensional columns was employed, in conjunction with temperature ramping, in a practical application to separate a mixture of plant emitted volatile organic compounds with significantly shortened analysis time.

Effect of Thermal Desorption Kinetics on Vapor Injection Peak Irregularities by a Microscale Gas Chromatography Preconcentrator

Analytical Chemistry. Aug, 2012  |  Pubmed ID: 22780835

Microscale gas chromatography (μGC) is an emerging analytical technique for in situ analysis and on-site monitoring of volatile organic compounds (VOCs) in moderately complex mixtures. One of the critical subcomponents in a μGC system is a microfabricated preconcentrator (μ-preconcentrator), which enables detection of compounds existing in indoor/ambient air at low (~sub ppb) concentrations by enhancing their signals. The prevailing notion is that elution peak broadening and tailing phenomena resulting from undesirable conditions of a microfabricated separation column (μ-column) are the primary sources of poor chromatographic resolution. However, previous experimental results indicate that the resolution degradation still remains observed for a μ-column integrated with other μGC subcomponents even after setting optimal separation conditions. In this work, we obtain the evidence that the unoptimized μ-preconcentrator vapor release/injection performance significantly contributes to decrease the fidelity of μGC analysis using our state-of-the-art passive preconcentrator microdevice. The vapor release/injection performance is highly affected by the kinetics of the thermal desorption of compounds trapped in the microdevice. Decreasing the heating rate by 20% from the optimal rate of 90 °Cs(-1) causes a 340% increase in peak tailing as well as 70% peak broadening (30% peak height reduction) to the microscale vapor injection process.

Bio-switchable Optofluidic Lasers Based on DNA Holliday Junctions

Lab on a Chip. Oct, 2012  |  Pubmed ID: 22790530

Bio-switchable optofluidic lasers based on DNA Holliday junctions were demonstrated. Nearly 100% wavelength switching was achieved through reversible conformational change of the Holliday junction controlled by magnesium ionic strength.

Metal-filled Carbon Nanotube Based Optical Nanoantennas: Bubbling, Reshaping, and in Situ Characterization

Nanoscale. Sep, 2012  |  Pubmed ID: 22875447

Controlled fabrication of metal nanospheres on nanotube tips for optical antennas is investigated experimentally. Resembling soap bubble blowing using a straw, the fabrication process is based on nanofluidic mass delivery at the attogram scale using metal-filled carbon nanotubes (m@CNTs). Two methods have been investigated including electron-beam-induced bubbling (EBIB) and electromigration-based bubbling (EMBB). EBIB involves the bombardment of an m@CNT with a high energy electron beam of a transmission electron microscope (TEM), with which the encapsulated metal is melted and flowed out from the nanotube, generating a metallic particle on a nanotube tip. In the case where the encapsulated materials inside the CNT have a higher melting point than what the beam energy can reach, EMBB is an optional process to apply. Experiments show that, under a low bias (2.0-2.5 V), nanoparticles can be formed on the nanotube tips. The final shape and crystallinity of the nanoparticles are determined by the cooling rate. Instant cooling occurs with a relatively large heat sink and causes the instant shaping of the solid deposit, which is typically similar to the shape of the molten state. With a smaller heat sink as a probe, it is possible to keep the deposit in a molten state. Instant cooling by separating the deposit from the probe can result in a perfect sphere. Surface and volume plasmons characterized with electron energy loss spectroscopy (EELS) prove that resonance occurs between a pair of as-fabricated spheres on the tip structures. Such spheres on pillars can serve as nano-optical antennas and will enable devices such as scanning near-field optical microscope (SNOM) probes, scanning anodes for field emitters, and single molecule detectors, which can find applications in bio-sensing, molecular detection, and high-resolution optical microscopy.

Intracavity DNA Melting Analysis with Optofluidic Lasers

Analytical Chemistry. Nov, 2012  |  Pubmed ID: 23017119

DNA melting analysis holds great promise for simple and fast DNA sequence discrimination. However, conventional fluorescence-based methods suffer from a small differential signal and demanding melting curve analysis, both of which make it difficult to distinguish the target DNA from the mismatched one. Herein, we propose and demonstrate a highly specific intracavity DNA melting analysis scheme utilizing an optofluidic laser. The laser optically amplifies the small yet intrinsic thermal dynamic difference between the target and the single-base-mismatched DNA, resulting in a differential signal that is orders of magnitude greater than with fluorescence-based methods. In particular, the existence of a phase transition between the stimulated laser emission and fluorescence (i.e., spontaneous emission) enables accurate determination of the DNA transition temperature difference. Furthermore, the high differential signal in the intracavity detection allows for scanning of the laser excitation at a fixed temperature to distinguish two DNA sequences, which provides another means for rapid DNA analysis. In this paper, we first theoretically investigate DNA melting analysis using an optofluidic laser and then experimentally explore this scheme with a high-quality optofluidic ring resonator. Distinction of two DNA sequences of up to 100 bases long is demonstrated. The intracavity detection developed here will lead to novel optofluidic devices that enable rapid and simple analysis of DNAs with very long sequences.

Periodic Plasmonic Enhancing Epitopes on a Whispering Gallery Mode Biosensor

Optics Express. Nov, 2012  |  Pubmed ID: 23187470

We propose the attachment of a periodic array of gold nanoparticles (epitopes) to the equator of a Whispering Gallery Mode Biosensor for the purpose of plasmonically enhancing nanoparticle sensing in a self-referencing manner while increasing the capture rate of analyte to antibodies attached to these plasmonic epitopes. Our approach can be applied to a variety of whispering gallery mode resonators from silicon/silica rings and disks to capillaries. The interpretation of the signals is particularly simple since the optical phase difference between the epitopes is designed to be an integer multiple of ?, allowing the wavelength shift from each binding event to add independently.

Fabry-Pérot Cavity Sensor-based Optofluidic Gas Chromatography Using a Microfabricated Passive Preconcentrator/injector

Lab on a Chip. Mar, 2013  |  Pubmed ID: 23295709

This study reports on dual on-column Fabry-Pérot (FP) cavity sensor-based gas chromatography (GC) of mixtures of volatile organic compounds (VOCs) utilizing an on-chip device, the so called "microfabricated passive preconcentrator/injector (μPPI)". Comprehensive analysis of the sampling, desorption/injection, and compound separation performance of the μPPI-based optofluidic GC system is described. Here, the combined use of the μPPI and on-column FP cavity sensors in a common GC platform enabled diffusion-based passive sampling, rapid (<7 min) chromatographic separation, and optical detection for the quaternary VOC mixtures of benzene, TCE, toluene, and m-xylene at sub-ppm concentrations with a simpler fluidic setup than conventional GC systems. The FP cavity sensor arrangement provided the means to study the dynamics of the thermal desorption/injection of VOCs by the μPPI and its effect on the GC separation resolution. Our analysis of obtained chromatograms revealed a presence of the competitive adsorptions of VOC mixtures onto the adsorption sites of trapping materials in the μPPI, which decreased the effective sampling rate by ~50% for compounds with high volatility. The validated performance of the optofluidic GC system promises future development of a field deployable GC microsystem incorporating the μPPI and the FP cavity sensors.

Smart Multi-channel Two-dimensional Micro-gas Chromatography for Rapid Workplace Hazardous Volatile Organic Compounds Measurement

Lab on a Chip. Mar, 2013  |  Pubmed ID: 23303462

We developed a novel smart multi-channel two-dimensional (2-D) micro-gas chromatography (μGC) architecture that shows promise to significantly improve 2-D μGC performance. In the smart μGC design, a non-destructive on-column gas detector and a flow routing system are installed between the first dimensional separation column and multiple second dimensional separation columns. The effluent from the first dimensional column is monitored in real-time and decision is then made to route the effluent to one of the second dimensional columns for further separation. As compared to the conventional 2-D μGC, the greatest benefit of the smart multi-channel 2-D μGC architecture is the enhanced separation capability of the second dimensional column and hence the overall 2-D GC performance. All the second dimensional columns are independent of each other, and their coating, length, flow rate and temperature can be customized for best separation results. In particular, there is no more constraint on the upper limit of the second dimensional column length and separation time in our architecture. Such flexibility is critical when long second dimensional separation is needed for optimal gas analysis. In addition, the smart μGC is advantageous in terms of elimination of the power intensive thermal modulator, higher peak amplitude enhancement, simplified 2-D chromatogram re-construction and potential scalability to higher dimensional separation. In this paper, we first constructed a complete smart 1 × 2 channel 2-D μGC system, along with an algorithm for automated control/operation of the system. We then characterized and optimized this μGC system, and finally employed it in two important applications that highlight its uniqueness and advantages, i.e., analysis of 31 workplace hazardous volatile organic compounds, and rapid detection and identification of target gas analytes from interference background.

Microring Resonators with Flow-through Nanopores for Nanoparticle Counting and Sizing

Optics Express. Jan, 2013  |  Pubmed ID: 23388915

This paper proposes a high precision method for nanoparticle counting and sizing using a microring resonator-waveguide system that contains a flow-through nanopore. Theoretical analysis is carried out based on the coupled-mode theory, showing that when the nanoparticle passes the nanopore a temporal pulse signal can be detected and that the peak amplitude depends linearly on the nanoparticle volume. It is estimated that a nanoparticle of sub-10 nm in size may be detectable.

Highly Sensitive Fluorescent Protein FRET Detection Using Optofluidic Lasers

Lab on a Chip. Jul, 2013  |  Pubmed ID: 23545541

We achieved optofluidic protein lasing using genetically encoded fluorescent protein FRET pairs linked by length-tunable peptides. Up to 25-fold reduction in the donor laser emission was observed when the donor and the acceptor were brought to close proximity, as compared to only 17% reduction in the donor emission using the conventional FRET detection. Our work opens a door to a broad range of applications in studying protein-protein interactions and protein-drug interactions.

Brillouin Cavity Optomechanics with Microfluidic Devices

Nature Communications. 2013  |  Pubmed ID: 23744103

Cavity optomechanics allows the parametric coupling of phonon- and photon-modes in microresonators and is presently investigated in a broad variety of solid-state systems. Optomechanics with superfluids has been proposed as a path towards ultra-low optical- and mechanical-dissipation. However, there have been no optomechanics experiments reported with non-solid phases of matter. Direct liquid immersion of optomechanics experiments is challenging, as the acoustic energy simply leaks out to the higher-impedance liquid surrounding the device. Here we confine liquids within hollow resonators to circumvent this issue and to enable optical excitation of mechanical whispering-gallery modes at frequencies ranging from 2 to 11,000 MHz. Our device enables optomechanical investigation with liquids, while light is conventionally coupled from the outer dry side of the capillary, and liquids are provided by means of a standard microfluidic inlet.

Smart Three-dimensional Gas Chromatography

Analytical Chemistry. Jul, 2013  |  Pubmed ID: 23789906

We developed a complete computer-controlled smart 3-dimensional gas chromatography (3-D GC) system with an automation algorithm. This smart 3-D GC architecture enabled independent optimization of and control over each dimension of separation and allowed for much longer separation time for the second- and third-dimensional columns than the conventional comprehensive 3-D GC could normally achieve. Therefore, it can potentially be employed to construct a novel GC system that exploits the multidimensional separation capability to a greater extent. In this Article, we introduced the smart 3-D GC concept, described its operation, and demonstrated its feasibility by separating 22 vapor analytes.

Self-assembled DNA Tetrahedral Optofluidic Lasers with Precise and Tunable Gain Control

Lab on a Chip. Sep, 2013  |  Pubmed ID: 23846506

We have applied self-assembled DNA tetrahedral nanostructures for the precise and tunable control of the gain in an optofluidic fluorescence resonance energy transfer (FRET) laser. By adjusting the ratio of the donor and the acceptor attached to the tetrahedral vertices, 3.8 times reduction in the lasing threshold and 28-fold enhancement in the lasing efficiency were demonstrated. This work takes advantage of the self-recognition and self-assembly capabilities of biomolecules with well-defined structures and addressability, enabling nano-engineering of the laser down to the molecular level.

Self-referencing Optofluidic Ring Resonator Sensor for Highly Sensitive Biomolecular Detection

Analytical Chemistry. Oct, 2013  |  Pubmed ID: 23992426

The noise-suppression techniques of label-free optical ring resonator sensors are crucial to improve their practical sensing capabilities for biochemical analysis and detection in extremely small detection concentration. We have developed a self-referencing optofluidic ring resonator (SR-OFRR) to vastly improve its sensing capability as a label-free optical biosensor. By monitoring the mode-splitting separation generated on a coupled ring resonator system, the common-mode noise is suppressed by 2 orders of magnitude without any external noise-suppression techniques. In this work, we first carried out theoretical analysis to elucidate the sensing principle and then applied the SR-OFRR biosensor to experimentally detect bovine serum albumin with a concentration detection limit on the order of 1 pg/mL (~15 fM).

In Situ Forming, Characterization, and Transduction of Nanowire Memristors

Nanoscale. Dec, 2013  |  Pubmed ID: 24162936

We report the nanorobotic in situ formation and characterization of memristors based on individual copper oxide nanowires (CuO NWs) and their potential applications as nanosensors with memory function (memristic sensors or "memsensors"). A series of in situ techniques for the experimental investigations of memristors are developed including nanorobotic manipulation, electro-beam-based forming, and electron energy loss spectroscopy (EELS) enabled correlation of transport properties and dopant distribution. All experimental investigations are performed inside a transmission electron microscope (TEM). The initial CuO NW memristors are formed by localized electron-beam irradiation to generate oxygen vacancies as dopants. Current-voltage properties show distinctive hysteresis characteristics of memristors. The mechanism of such memristic behavior is explained with an oxygen vacancy migration model. The presence and migration of the oxygen vacancies is identified with EELS. Investigations also reveal that the memristic behavior can be influenced by the deformation of the nanowire, showing that the nanowire memristor can serve as a deformation/force memorable sensor. The CuO NW-based memristors will enrich the binary transition oxide family but hold a simpler and more compact design than the conventional thin-film version. With these advantages, the CuO NW-based memristors will not only facilitate their applications in nanoelectronics but play a unique role in micro-/nano-electromechanical systems (MEMS/NEMS) as well.

The Potential of Optofluidic Biolasers

Nature Methods. Feb, 2014  |  Pubmed ID: 24481219

Optofluidic biolasers are emerging as a highly sensitive way to measure changes in biological molecules. Biolasers, which incorporate biological material into the gain medium and contain an optical cavity in a fluidic environment, can use the amplification that occurs during laser generation to quantify tiny changes in biological processes in the gain medium. We describe the principle of the optofluidic biolaser, review recent progress and provide our outlooks on potential applications and directions for developing this technology.

Optofluidic Laser for Dual-mode Sensitive Biomolecular Detection with a Large Dynamic Range

Nature Communications. 2014  |  Pubmed ID: 24781061

Enzyme-linked immunosorbent assay (ELISA) is a powerful method for biomolecular analysis. The traditional ELISA employing light intensity as the sensing signal often encounters large background arising from non-specific bindings, material autofluorescence and leakage of excitation light, which deteriorates its detection limit and dynamic range. Here we develop the optofluidic laser-based ELISA, where ELISA occurs inside a laser cavity. The laser onset time is used as the sensing signal, which is inversely proportional to the enzyme concentration and hence the analyte concentration inside the cavity. We first elucidate the principle of the optofluidic laser-based ELISA, and then characterize the optofluidic laser performance. Finally, we present the dual-mode detection of interleukin-6 using commercial ELISA kits, where the sensing signals are simultaneously obtained by the traditional and the optofluidic laser-based ELISA, showing a detection limit of 1 fg ml(-1) (38 aM) and a dynamic range of 6 orders of magnitude.

Understanding the Electrochemical Mechanism of K-αMnO2 for Magnesium Battery Cathodes

ACS Applied Materials & Interfaces. May, 2014  |  Pubmed ID: 24807043

Batteries based on magnesium are an interesting alternative to current state-of-the-art lithium-ion systems; however, high-energy-density cathodes are needed for further development. Here we utilize TEM, EDS, and EELS in addition to soft-XAS to determine electrochemical magnesiation mechanism of a high-energy density cathode, K-αMnO2. Rather than following the typical insertion mechanism similar to Li(+), we propose the gradual reduction of K-αMnO2 to form Mn2O3 then MnO at the interface of the cathode and electrolyte, finally resulting in the formation of K-αMnO2@(Mg,Mn)O core-shell product after discharge of the battery. Understanding the mechanism is a vital guide for future magnesium battery cathodes.

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