Yuze Sun

Sensitive optical biosensors for unlabeled targets : A review

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.

Optical ring resonators for biochemical and chemical sensing

AbstractIn 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. FigureVarious types of optical ring resonators for biochemical and chemical sensing

Bioinspired optofluidic FRET lasers via DNA scaffolds

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/mm2. 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.

On-Column Micro Gas Chromatography Detection with Capillary-Based Optical Ring Resonators

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.

Versatile opto-fluidic ring resonator lasers with ultra-low threshold

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 RIs 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.

Rapid chemical-vapor sensing using optofluidic ring resonators

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.

Analysis of ring resonators for chemical vapor sensor development

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.

Highly sensitive fluorescent protein FRET detection using optofluidic lasers

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.

Distinguishing DNA by Analog‐to‐Digital‐like Conversion by Using Optofluidic Lasers

Distinguishing a target DNA from a counterpart that has a single base mismatch provides critical information for disease diagnosis, personalized medicine, and basic biochemical research. In traditional, fluorescence-based detection, samples are placed in a cuvette, and a DNA probe is used to hybridize with the target DNA and generate a fluorescent signal. However, because of the small difference in the binding affinity for the DNA probe between the target and the strand with a single base mismatch, the discrimination ratio between the resulting fluorescence is almost unity, which makes it difficult to directly and selectively detect the target DNA from a pool of mismatched DNA strands. Herein, we describe a system for the highly specific intracavity detection of DNA that uses an optofluidic laser. This type of laser is an emerging technology that synergistically integrates a dye laser and microfluidics for miniaturized laser sources, easy sample delivery, and extremely small sample volumes. In our detection system, DNA samples and probes are incorporated as part of the laser gain medium. Stimulated laser emission, rather than fluorescence (that is, spontaneous emission), is employed as the sensing signal to achieve conversion that is similar to analog-to-digital, which significantly amplifies the small intrinsic thermodynamic difference between the target and its single base mismatched counterpart. A perfectly matched (PM) DNA, a single base mismatched (SM) DNA, and a molecular beacon (MB) probe were used as a model system. A theoretical analysis was performed to elucidate the underlying intracavity detection principle. Then, a discrimination ratio (that is, R = IPM/ISM, where IPM and ISM is the light intensity generated by PM DNA and SM DNA, respectively) of 240:1 was achieved experimentally between PM DNA and SM DNA, which is an increase of over two orders of magnitude relative to the fluorescence-based method. The selective detection of PM DNA from a pool of SM DNA at a concentration ratio of 1:50 is presented. This system can also distinguish more complicated DNA sequences, such as a breast cancer sequence from a corresponding sequence that contains a single point mutation, in both buffer and serum. An MB is a DNA probe with a stem-loop structure and a dye as well as a quencher attached to each end of the sequence (Figure 1a). 14–17] Both PM DNA and SM DNA are able to hybridize with the MB. Consequently, a fraction of MBs open and generate fluorescence. This fluorescencebased detection (see the detailed analysis in Section I A in the

Highly versatile fiber-based optical Fabry-Pérot gas sensor

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.