Tapered Optical Fiber Sensor for Label-Free Detection of Biomolecules

This paper presents a fast, highly sensitive and low-cost tapered optical fiber biosensor that enables the label-free detection of biomolecules. The sensor takes advantage of the interference effect between the fiber’s first two propagation modes along the taper waist region. The biomolecules bonded on the taper surface were determined by demodulating the transmission spectrum phase shift. Because of the sharp spectrum fringe signals, as well as a relatively long biomolecule testing region, the sensor displayed a fast response and was highly sensitive. To better understand the influence of various biomolecules on the sensor, a numerical simulation that varied biolayer parameters such as thickness and refractive index was performed. The results showed that the spectrum fringe shift was obvious to be measured even when the biolayer was only nanometers thick. A microchannel chip was designed and fabricated for the protection of the sensor and biotesting. Microelectromechanical systems (MEMS) fabrication techniques were used to precisely control the profile and depth of the microchannel on the silicon chip with an accuracy of 2 μm. A tapered optical fiber biosensor was fabricated and evaluated with an Immune globulin G (IgG) antibody-antigen pair

Optical Microfibre Based Photonic Components and Their Applications in Label-Free Biosensing

Optical microfibre photonic components offer a variety of enabling properties, including large evanescent fields, flexibility, configurability, high confinement, robustness and compactness. These unique features have been exploited in a range of applications such as telecommunication, sensing, optical manipulation and high Q resonators. Optical microfibre biosensors, as a class of fibre optic biosensors which rely on small geometries to expose the evanescent field to interact with samples, have been widely investigated. Due to their unique properties, such as fast response, functionalization, strong confinement, configurability, flexibility, compact size, low cost, robustness, ease of miniaturization, large evanescent field and label-free operation, optical microfibres based biosensors seem a promising alternative to traditional immunological methods for biomolecule measurements. Unlabeled DNA and protein targets can be detected by monitoring the changes of various optical transduction mechanisms, such as refractive index, absorption and surface plasmon resonance, since a target molecule is capable of binding to an immobilized optical microfibre. In this review, we critically summarize accomplishments of past optical microfibre label-free biosensors, identify areas for future research and provide a detailed account of the studies conducted to date for biomolecules detection using optical microfibres

Microfiber Coupler Based Label-Free Immunosensor

Optical microfibers and related structures which incorporate large evanescent field and minimal size offer new opportunities for biosensing applications. In this paper we report the development of an immunosensor based on a tapered microfiber coupler embedded in a low refractive index polymer. Biomolecules adsorbed on the microfiber coupler surface modify the surrounding refractive index. By immobilizing antigens on the surface of the sensing area, the microfiber coupler was able to operate as a label-free immunosensor to detect specific antibodies. We experimentally demonstrated for the first time the sensing ability of this sensor using a fibrinogen antigen-antibody pair. By monitoring the spectral shift in the wavelength domain, the sensor was shown to be capable of detecting the specific binding between fibrinogen and anti-fibrinogen. The detected signal was found to be proportional to the anti-fibrinogen present

Rapid Detection of SARS-CoV-2 Nucleocapsid Protein by a Label-Free Biosensor Based on Optical Fiber Cylindrical Micro-Resonator

The current global outbreak of coronavirus (COVID-19) continues to be a severe threat to human health. Rapid, low-cost, and accurate antigen detection methods are very important for disease diagnosis. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) nucleocapsid protein (N-Protein) is often used as the diagnostic and screening for coronavirus detection. To this end, we propose and experimentally validate a highly sensitive whispering gallery mode (WGM) optical cylindrical micro-resonator (CMR) for bio immunoassay detection. To study the biokinetic process of immunoassay, the surface of the WGM micro-resonator is functionalized with N-Protein monoclonal antibody (N-Protein-m Ab), which led to the specific detection of N-Proteins. The spectral characteristics of the WGM resonance dip were investigated, and it is found that the transmission spectrum of WGM shows a monotonically increasing red-shift as a function of recording time. The WGM red-shift is due to the antibody-antigen reaction and can be used for the analysis of the immunoassay process. The wavelength shift is shown to be proportional to the concentration of N-Protein, which ranges between 0.1 and 100 μg /mL. Finally, different types of samples (concentration of 10 μg /mL of N-Protein) were prepared and tested to simulate the specificity of the sensor in the practical application environment. This method has the merits of a rapid assay, lower expense, easy preparation, and miniaturization, which makes the sensor have the potential for broad applications in the field of biochemistry and biomedical detection

Creation of novel gold-nanorod-based localized surface plasmon resonance biosensors

Starting with a comprehensive review of both surface plasmon resonance (SPR) based and localized surface plasmon resonance (LSPR) based sensors, this thesis reports the studies on the development of a novel sensitive gold nanorod (GNR) based label-free LSPR optical fibre biosensor, and the development of a novel robust method for effectively modifying the surface of cetyl-trimethyl ammonium bromide (CTAB) capped GNRs and their LSPR biosensing applications. A novel GNR-based LSPR optical fibre sensor was fabricated and evaluated in this work. The sensor probe was prepared by covalently immobilizing GNRs, synthesized using a seed-mediated growth method, on the decladed surface of a piece of multimode optical fibre. In order to operate the LSPR sensor as a reflective sensor, a silver mirror was also coated at one distal end of the sensor probe by a dip coating method. In the refractive index sensitivity test, it was found that the longitudinal plasmon band (LPB) of GNRs is highly sensitive to the refractive index change close to the GNRs surface, and the sensitivity of the LSPR optical fibre sensor increases with the increase of the aspect ratio of GNRs. The results showed that the GNR-based LSPR optical fibre sensors prepared in this work have linear and high refract index sensitivities. For sensors based on GNRs with aspect ratios of 2.6, 3.1, 3.7 and 4.3, their refractive index sensitivities were found to be 269, 401, 506 and 766 nm/RIU (RIU = refractive index unit), respectively, in the refractive index range from 1.34 to 1.41. In order to evaluate the biosensing performance, the GNR-based LSPR optical fibre sensor with aspect ratio of 4.1 and a 2 cm sensing length was further functionalized with human IgG to detect the specific target — anti-human IgG, and a detection limit of 1.6 nM was observed using a wavelength-based interrogation approach. In another study, in order to overcome the drawbacks of the CTAB-capped GNRs found in biosensing and biomedical applications, a simple yet robust pH-mediated method for effectively modifying the surface of CTAB-capped GNRs synthesized by the seed-mediated growth method was developed. This method allows the complete replacement of the CTAB molecules attached on the GNRs surface with the 11-mercaptoundecaonic acid (MUA) molecules to take place in a total aqueous environment by controlling the pH of the MUA aqueous solution, thus avoiding the irreversible aggregation of GNRs during the complex surface modification process observed in the previous reported methods. The success of the complete replacement of CTAB with MUA was confirmed by the surface elemental analysis using an X-ray photoelectron spectroscopy (XPS), and the MUA-modified GNRs created in this work demonstrated a high stability up to 4 months at least when stored in a buffer solution at pH 9 at 4°C. The MUA-modified GNRs with an aspect ratio of 3.9 were furthered developed as a solution-phase-based label-free LSPR biosensor by functionalizing the GNRs with human IgG. A detection limit as low as 0.4 nM for detecting anti-human IgG was achieved by this sensor. The achievements of this work are concluded and the directions of future work are also pointed out

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

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

Evanescent single-molecule biosensing with quantum limited precision

Sensors that are able to detect and track single unlabelled biomolecules are an important tool both to understand biomolecular dynamics and interactions at nanoscale, and for medical diagnostics operating at their ultimate detection limits. Recently, exceptional sensitivity has been achieved using the strongly enhanced evanescent fields provided by optical microcavities and nano-sized plasmonic resonators. However, at high field intensities photodamage to the biological specimen becomes increasingly problematic. Here, we introduce an optical nanofibre based evanescent biosensor that operates at the fundamental precision limit introduced by quantisation of light. This allows a four order-of-magnitude reduction in optical intensity whilst maintaining state-of-the-art sensitivity. It enable quantum noise limited tracking of single biomolecules as small as 3.5 nm, and surface-molecule interactions to be monitored over extended periods. By achieving quantum noise limited precision, our approach provides a pathway towards quantum-enhanced single-molecule biosensors.Comment: 17 pages, 4 figures, supplementary informatio

Fiber Optic Sensing with Lossy Mode Resonances: Applications and Perspectives

This review focuses on the recent advances in lossy more resonance (LMR) fiber optic sensors. LMR sensors present many interesting features also in comparison with surface plasmon resonance (SPR), the most widespread resonance-based sensing platform. Two key parameters determine the performance of LMR sensors: geometrical configuration and material supporting the LMR. After reviewing those aspects and some fundamentals of the theory, the review focuses on the sensing mechanisms, mainly based on refractometry, and their possible applications. Many examples from the literature are reported ranging from electric field to pressure sensors and from gas detection to biosensors. Such vibrant activity on LMR sensors confirms the potentiality of this technology making it a very promising platform for sensor development