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Dual-core all-fiber integrated immunosensor for detection of protein antigens
Abstract
An optical fiber interferometric microprobe for detection of specific proteins is presented in this paper. The microprobe is an all-fiber device, which is based on Michelson interferometer configuration, which allows for detection of protein antigens in an analyzed solution thanks to antibodies immobilized on the sensor surface. The interferometer is made of dual core fiber and has a precisely formed arm length difference, achieved by splicing a fragment of polarization maintaining fiber to one of the cores. An all-fiber configuration of the sensor decreases substantially cross-sensitivities to temperature and deformation in comparison to other optical fiber interferometers. Reported sensor has a sensing region on the tip of the interferometer and therefore may be used for point measurements in medicine. The immunosensor and optical measuring system are designed to utilize the most common broadband light sources that operate at a central wavelength of 1.55 µm. The results show that it is possible to detect a protein antigen present in a solution by using an all-fiber interferometer coated with specific antibodies. The resulting peak shift can reaches 0.6 nm, which is sufficient to be measured by an optical spectrum analyzer or a spectrometer. A model allowing for estimation of the value of lower limit of detection for such sensors has been elaborated. The elaborated detection system may act as a framework for detection of various antigens and thus it can find future applications in medical diagnostics.
... where L is the propagation length of both light beam 1 and light beam 2. To date, there are three coupling methods used for protein biosensing, including employing long-period grating [112], waist-enlarged fusion taper [113], and dual-core fiber [114]. Usually, the sensing region is located at the fiber surface, and the bio-reaction will change the effective RI of the cladding mode. ...
... Usually, the sensing region is located at the fiber surface, and the bio-reaction will change the effective RI of the cladding mode. In 2018, Wysokiński et al. demonstrated a dual-core all-fiber (DCF) configuration for protein antigen detection, achieving a peak shift of 0.6 nm [114]. Figure 8b is the SEM image of DCF; since the cores are closer to each other, the sensor exhibits good resistance to temperature and stain changes. ...
... where L is the propagation length of both light beam 1 and light beam 2. To da are three coupling methods used for protein biosensing, including employing lon grating [112], waist-enlarged fusion taper [113], and dual-core fiber [114]. Usu sensing region is located at the fiber surface, and the bio-reaction will change the RI of the cladding mode. ...
Proteins play an important role in organisms. The fast and high-accuracy detection of proteins is demanded in various fields, such as healthcare, food safty, and biosecurity, especially in the background of the globally raging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Optical fiber sensors have great potential for protein detection due to the excellent characteristics of high sensitivity, miniaturization, and capability for remote monitoring. Over the past decades, a large number of structures have been investigated and proposed. This paper begins with an overview of different fiber sensing structures for protein detection according to the fundamental sensing mechanisms. The overview is classified into four sections, including intensity-modulation, phase-modulation, scattering, and fluorescence. In each section, we reviewed the recent advances of fiber protein sensors and compared their performance, such as sensitivity and limit of detection. And then we analyzed the advantages and disadvantages of the four kinds of biosensors. Finally, the paper concludes with the challenges faced and possible future development of optical fiber protein biosensors for further study.
... The fabrication of miniaturized and integrated in-fiber devices of an optical system has driven a lot of research interest [1][2][3][4][5]. Since the birth of photonic crystal fibers (PCFs) in 1995, PCF has been extensively practiced in many fields, such as biosensors [6], passive optical devices [7,8], and medicine [3], owing to its structural flexibility [9][10][11][12]. ...
... The PWDT property is caused by the surface plasmon polariton (SPP), which is excited at the metal-dielectric interface due to the stimulation of light. Consequently, this phenomenon has already been studied in many potential applications including polarizers [16][17][18][19][20], sensors [4,6,21], and in-fiber devices [2,5,22]. ...
This work demonstrates a broadband polarization filter based on copper-filled photonic crystal fiber (CFPCF). The proposed fiber is fabricated using the conventional stack-and-draw method. The polarization filter properties of the proposed CFPCF are investigated numerically by considering the cross-sectional scanning electron microscopy image of the fabricated CFPCF. It is observed that the magnitude of cross talk reached up to over 0.8 mm length with a broad bandwidth of 282 nm at a central wavelength of 1790 nm. In addition, the polarization characteristics of the CFPCF including cross talk, central wavelength, and bandwidth can be adjusted by varying the diameter of the copper wire. It is shown that the resonance wavelength of the proposed filter can be tuned over the wide range of wavelengths from 1390 to 1890 nm. We have shown that by adjusting the copper wire diameter to and ( is pitch size), the proposed filter can operate at communication bands of 1310 and 1550 nm, respectively. The results suggest high-potential of the proposed fiber for polarization filtering and other sensing applications.
... One of the simplest realization of all-optical signal switching is based on dual-core fibers with principle of nonlinear directional coupler performance [3]. Even tough, the dual-core fibers (DCFs) development was motivated also by further applications including lasers [4] sensors [5] and polarization splitters [6], just a limited amount of experimental studies were devoted to communication technology proposes [7]. Despite alternative devices like metamaterial-based ones or ring resonators, DCFs remain favorable due to their simple fabrication and easy cascading potential, leading to compact and cost-effective devices [8]. ...
... 98 Wysokinśki et al. proposed a fiber optic MI sensor for the detection of specific proteins, antigens, and biologically relevant molecules. 99 The interferometer was made using DCF with a tapered form having two arms with a precise length difference between them. This was achieved by splicing a fragment of polarization-maintaining fiber (PMF) onto one of the fiber ends. ...
Over the last 20 years, optical fiber-based devices have been exploited extensively in the field of biochemical sensing, with applications in many specific areas such as the food processing industry, environmental monitoring, health diagnosis, bioengineering, disease diagnosis, and the drug industry due to their compact, label-free, and highly sensitive detection. The selective and accurate detection of biochemicals is an essential part of biosensing devices, which is to be done through effective functionalization of highly specific recognition agents, such as enzymes, DNA, receptors, etc., over the transducing surface. Among many optical fiber-based sensing technologies, optical fiber interferometry-based biosensors are one of the broadly used methods with the advantages of biocompatibility, compact size, high sensitivity, high-resolution sensing, lower detection limits, operating wavelength tunability, etc. This Review provides a comprehensive review of the fundamentals as well as the current advances in developing optical fiber interferometry-based biochemical sensors. In the beginning, a generic biosensor and its several components are introduced, followed by the fundamentals and state-of-art technology behind developing a variety of interferometry-based fiber optic sensors. These include the Mach–Zehnder interferometer, the Michelson interferometer, the Fabry–Perot interferometer, the Sagnac interferometer, and biolayer interferometry (BLI). Further, several technical reports are comprehensively reviewed and compared in a tabulated form for better comparison along with their advantages and disadvantages. Further, the limitations and possible solutions for these sensors are discussed to transform these in-lab devices into commercial industry applications. At the end, in conclusion, comments on the prospects of field development toward the commercialization of sensor technology are also provided. The Review targets a broad range of audiences including beginners and also motivates the experts helping to solve the real issues for developing an industry-oriented sensing device.
... The phenomenon of SPR can be observed when the TM-polarized light is reflected from the BK7 coupling prism. The resulting reflectance curve, known as the SPR signal, is highly responsive to changes in the refractive index of the sensing medium (n s ), making it widely applicable in biosensing, as well as in chemical and environmental monitoring [53][54][55]. Our results indicate that the SPR detection signal of the Au-based sensor ( In recent year, 2D materials have been investigated for their potential application in SPR sensors due to their adsorption characteristics [20]. ...
The surface plasmon resonance (SPR) signal, generated from the Kretschmann configuration, has been developed as an effective detection technology in chemical and biological sensors. The sensitivity of SPR signals to changes in the surrounding media makes it a valuable tool, as even a slight variation in refractive index can cause a significant change in SPR signals, such as phase, intensity, and resonance angle. However, the detection of ultralow changes in refractive index, which occur in chemical reactions or biological actions, remains a challenge for conventional SPR sensors due to their limited sensitivity. To overcome this limitation, we theoretically propose a novel guided-wave SPR (GWSPR) configuration coated with a few-layer blue phosphorene (blueP)/MoS2 hybrid structure. This configuration aims to enhance the electric field and subsequently achieve a significant improvement in sensitivity. The results of our study demonstrate that the proposed blueP/MoS2-based GWSPR sensor exhibits a high sensitivity of 290°/RIU, which represents an impressive enhancement of approximately 82.4% compared to the conventional Au-based SPR sensor. This advancement addresses the challenge of detecting ultralow changes in refractive index and offers significant potential for enhancing the performance of chemical and biological sensors.
... As another example, Wysokinski et al. proposed an MI-based biosensor using a dualcore fiber to detect protein antigens [92]. One of the fiber cores was spliced with polarization maintaining fiber with fixed length to introduce precise arm length difference, while the other core was functionalized by immobilization of IgG on the fiber end using crosslinking reagents. ...
Biosensing and bioimaging are essential in understanding biological and pathological processes in a living system, for example, in detecting and understanding certain diseases. Optical fiber has made remarkable contributions to the biosensing and bioimaging areas due to its unique advantages of compact size, immunity to electromagnetic interference, biocompatibility, fast response, etc. This review paper will present an overview of seven common types of optical fiber biosensors and optical fiber-based ultrasound detection in photoacoustic imaging (PAI) and the applications of these technologies in biosensing and bioimaging areas. Of course, there are many types of optical fiber biosensors. Still, this paper will review the most common ones: optical fiber grating, surface plasmon resonance, Sagnac interferometer, Mach–Zehnder interferometer, Michelson interferometer, Fabry–Perot Interferometer, lossy mode resonance, and surface-enhanced Raman scattering. Furthermore, different optical fiber techniques for detecting ultrasound in PAI are summarized. Finally, the main challenges and future development direction are briefly discussed.
... SEM picture of the cross-section of the manufactured microstructured dual-core fiber. A similar fiber was used in[30]. ...
In this work, a compact all-fiber bend sensor based on a dual-core microstructured optical fiber has been manufactured and characterized. The sensor relies on the unbalanced Michelson interferometric technique realized by attaching a piece of silica fiber to one of the fiber cores acting as the unbalancing element. Three probes with different lengths of the unbalancing element have been experimentally tested for sensitivity tailoring analysis. Additionally, a theoretical model has been developed for comparison and verification of the results. Good linear behavior of the spectral shift with bend has been measured and it has been proven that the sensitivity of the sensor depends on the length of the unbalancing element and the orientation of the cores. Higher sensitivities are achieved for shorter lengths of the unbalancing element and orientation of the core axis parallel to the bend direction. The highest sensitivity reported is 9.97 pm/µm for the case of 34 µm of unbalancing element and orientation of 0 degrees.
... Note that these layers include the antigen coating and any antibodies that could have attached to the functionalized PDMS surface. Hence, considering that the tests were performed with the same immunosensors, the thickness difference could be attributed to changes in the PDMS end-cap surface owing to antigen-antibody binding effects, as resported previously for other bio-sensing platforms [9,38]. ...
We demonstrate a novel and simple means to fabricate optical fiber immunosensors based on Fabry-Perot (F-P) interferometers using polydimethylsiloxane (PDMS) as support for bioactive lipids. The sensors are fabricated following a straightforward dip-coating method producing PDMS end-capped devices. A biosensing platform is realized by subsequent functionalization of the PDMS cap with a previously characterized bioactive lipid antigen cocktail from Mycobacterium fortuitum, used as a surrogate source of antigens for tuberculosis diagnosis. After functionalization of the PDMS, the F-P sensors were immersed in different antibody-containing sera and the registered changes in their spectral features were associated to the interactions between the active lipids and the serum antibodies. Our results show that the proposed PDMS end-capped F-P immunosensors perform well differentiating antibody-containing sera. Furthermore, they offer attractive attributes such as label-free operation, real-time detection capabilities and they are also reusable. The proposed sensors, therefore, serve as an enabling optical immunosensing technique offering excellent potential for developing novel lipidomic analytical tools.
... They have become an alternative to conventional measurement methods due to their excellent properties, such as high sensitivity and wide dynamic range of measurements or resistance to ionizing radiation. They are used in the automotive industry [2], aviation and marine [3], power engineering [4], chemistry [5] and medicine [6]. They are used to measure values of physical and chemical quantities, such as: temperature [7,8], refractive index [9e11], pH [12,13], pressure [14,15], displacement [16,17], stress [18,19] and others [20e25]. ...
Fiber-optic sensors find numerous applications in science and industry, but their full potential is limited because of the risk of damaging the measurement head, in particular, due to the vulnerability of unprotected tips of the fiber to mechanical damage and aggressive chemical agents. In this paper, we report the first use of a new nanocrystalline diamond structure in a fiber-optic measurement head as a protective coating of the fiber tip. The nanocrystalline sheet structures, produced with the use of Microwave Plasma Assisted Chemical Vapor Deposition System (MW PA CVD), were characterized by Scanning Electron Microscopy (SEM) and successfully transferred from the deposition substrate onto the surface of the tip of a single-mode fiber sensor head. A Fabry-Perot sensing interferometer for distance measurement comprising that fiber was built. The measurement results were compared with numerical modeling. High values of achieved correlation coefficients (R2 > 0.99) between a linear model and distance measurements data indicate that the diamond sheet does not affect the correct operation of the sensor while extending its potential scope of applications.
In this dissertation, a study of pulse energy-controlled solitonic steering of femtosecond pulses in highly nonlinear dual-core fibers is presented. It targets a specific area of ultrafast nonlinear fiber optics and also the general soliton theory in coupled waveguides, with high application potential in all-optical signal processing. The goal of the dissertation is to prove that specially designed dual-core fibers made of soft-glass materials support an energy-driven switching of femtosecond pulses. The fiber is made of a pair of two thermally matched glasses: a lead silicate (highly nonlinear) and borosilicate glasses for the cores and cladding, respectively. They have high contrast of the refractive indices at the level of 0.4 in the near infrared. The physical principle that allows the switching performance is the nonlinear self-trapping of high-order solitons, which is induced by the nonlinear Kerr effect in the core glass.
The first part of the dissertation shows the numerical study of the fiber structure
optimization in terms of its dispersion and coupling properties. Two alternatives are
studied: all-solid photonic crystal dual-core fiber and all-solid dual-core fiber with homogeneous cladding. Then, the numerical simulation results of the nonlinear propagation of femtosecond pulses with energies in the picojoule range are presented. The goal is to determine the wavelength and temporal width of hyperbolic secant pulses which support the optimal switching performance. They are in the range 1400 - 1800 nm and 75 - 150 fs, respectively. The optimal switching performance is identified in terms of highest switching contrast parameter, which indicates the capability of the excited pulse to exchange core during propagation. The optimal switching performance is predicted for a 43 mm all-solid dual-core fiber with simple cladding and 3.2 μm distance between the cores. The excitation pulses have 1500 nm wavelength, 75 fs temporal width and in-coupled energies at the level of only 20 pJ. The highest switching contrast is 46 dB calculated in the time window of the ultrashort pulses. Moreover, the predicted switching performance is uniform over 200 nm in the spectral domain. Afterwards, the dissertation proceeds with a brief description of the fabrication process of the optimized dual-core fiber. It is based on the stack-and-draw method. Then, the structure of the fabricated fiber is analyzed in terms of dual-core asymmetry. It is related to the difference between the shapes of the two cores. It is always present after the fabrication process because of the intrinsic thermodynamic fluctuation of the drawing parameters. Therefore, its influence on the coupling properties of the fiber, on the ultrafast pulse propagation, as well on the switching performance, is examined.
The second part of the dissertation presents the experimental results of self-switching, i.e. energy-driven nonlinear switching, using femtosecond pulses at wavelength of 1560 and 1700 nm. Two sets of all-solid dual-core fibers with the optimized structural parameters and different levels of dual-core symmetry were used. The following outcomes were demonstrated: 1) reversible switching performance of 1560 nm sub-nJ pulses, with soliton-like character (confirmed by numerical simulations); 2) switching performance at 1700 nm of pulses with 1-3 nJ input energy; it shows a two-time exchange of the core with a maximal switching contrast of 16.7 dB and it is broadband in a spectral window of 150 nm. In the frame of the study of the fiber length effect, the highest switching contrast of 20.1 dB at 35 mm fiber length is demonstrated at 1560 nm. The switching performance is observed in a broadband spectral range between 1450 and 1650 nm. In the case of 1700 nm excitation wavelength, the highest switching contrast is 20.6 dB at 40 mm. It is accompanied by multiple exchanges of the dominant core, which is a strong indication of the soliton-based switching process. Both reported outcomes rely on the lower dual-core asymmetry of the all-solid fiber than the one of the standard air-hole dual-core fiber, which was investigated previously.
Finally, in the last part of the dissertation a novel switching approach is presented:
the so-called dual wavelength approach. It is based on the cross-interaction between
two synchronized femtosecond pulses with different wavelengths: signal (1560 nm) and control (1030 nm). The adjustment of the control pulse energy enables the signal pulse to switch between the cores. The novel switching approach is based on the physical process of nonlinear balancing of dual-core asymmetry: the control pulse induces a group velocity reduction of the signal pulse, which finally switches between the cores. Switching contrasts of more than 25 dB and a shift of the signal central wavelength of only 3 nm were recorded using fibers with optimized lengths below only 20 mm. These results were confirmed also by the spectra recordings at the fiber output.
Thanks to the improved dual-core symmetry, the fiber design without microstructure
and fabricated with the all-solid approach allows an efficient switching capability of
optical soliton-like pulses. Moreover, it can have some practical applications in optical
communications as fiber-based, low-power, compact and simple all-optical switching
device.
Optical fiber biosensors have attracted extensive research attention in fields such as public health research, environmental science, bioengineering, disease diagnosis and drug research. Accurate detection of biomolecules is essential to limit the extent of disease outbreaks and provide valuable guidance for regulatory agencies to take timely measures. Among many optical fiber sensors, optical fiber biosensors based on specialty fibers have the advantages of biocompatibility, small size, high measurement resolution, high stability, and immunity to electromagnetic interference. In this paper, four types interferometer biosensors based on specialty fiber, namely Mach‐Zehnder interferometer (MZI), Michelson interferometer (MI), Fabry ‐ Perot interferometer (FPI) and Sagnac interferometer (SI), are reviewed in terms of operating principles, sensing structure, and application fields. The fiber types are further divided into micro‐nano optical fiber, thin core fiber, polarization maintaining fiber, polymer fiber, microstructure optical fiber. Furthermore, this paper evaluates the advantages and disadvantages of these interferometer biosensors. Finally, main challenging problems and expectational development direction of specialty fiber interferometer biosensors are summarized. This text clearly shows the huge development potential of optical fiber biosensors in biomedical.
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With few-layer black phosphorus (BP)-based one-dimensional photonic crystal (1DPC), a novel optical biosensor based on the guided-mode resonance (GMR) is proposed for enhancing the sensitivity. Due to the strong coupling of the GMR with itself, the resonance dip of GMR signal will split into more resonance dips with the addition of basic constituent unit. The resonance dips are found to be deeper and deeper to enhance the resonance with the addition of period of 1DPC. Of particular interest is that the enhanced GMR signal can produce a contribution to improve the sensitivity of the biosensor. Therefore, the ultrasensitive GMR biosensor with few-layer BP-based 1DPC is designed to get a high sensitivity (Smax = 20683 RIU
-1
). For a comparison to the conventional surface plasmon resonance (SPR) sensor (Smax = 59 RIU
-1
), the sensitivity of the proposed GMR sensor has been enhanced 350 times. The BP-based 1DPC configuration, which could be developed as a promising replacement of metallic thin film, has enriched the application of GMR phenomenon in the biosensing technologies.
In recent years, label-free biosensors not requiring external modifications have been receiving intense attention. A label-free optical biosensor, which retains many of the desirable features of conventional surface plasmon resonance (SPR) reflectometry, namely, the ability to monitor the kinetics of biomolecular interactions in real-time without a label has been developed with several important advantages: the biosensor device is easy to fabricate, and simple to implement, requiring only an UV–Vis spectrophotometer or flatbed scanner. Importantly, the label-free optical biosensor can be easily multiplexed to enable high-throughput monitoring of biomolecular interactions in an array-based format. In this research, the development of a localized surface plasmon resonance (LSPR)-based label-free optical biosensor using a surface modified nanoparticle layer is aimed. This optical detection method promises to offer a massively parallel detection capability in a highly miniaturized package. The two-dimensional nanoparticle layer was formed by the surface modified silica nanoparticles. The optical properties and surface analysis of nanoparticle layer substrate were characterized through transmission measurements and atomic force microscopy (AFM). Simultaneously, the nanoparticle layer substrate was applied to the optical LSPR-based biosensor for label-free monitoring of the antigen–antibody reaction. The anti-fibrinogen antibody was immobilized onto the nanoparticle layer substrate surface. Different concentrations of fibrinogen were introduced to the anti-fibrinogen antibody immobilized nanoparticle layer substrate surface, and the change in the absorption spectrum, caused by the antigen–antibody reaction, was observed. By using this anti-fibrinogen antibody immobilized nanoparticle layer substrate; the detection limit of this optical LSPR-based biosensor was 10 ng/ml.
The main obstacle in realization of a totally implantable hearing aid is a lack of reliable implantable microphone. In this paper we have described a potentially miniature fiber-optic vibrometer based on a modified Michelson interferometer, designed to serve as a middle-ear microphone for totally implantable cochlear- or middle-ear hearing aids. A model of the sensing system was used for in-vitro and in-vivo investigation of acoustical response of sheep's middle-ear ossicles. Surgical and implantation procedure of introducing the sensing optical fiber into the middle-ear and its aiming at the incus was investigated and described here in detail. The frequency responses of the incus was measured while a cadaver and living sheep was exposed to the sinusoidal acoustical excitation of 40-90dB SPL, in the frequency range from 100Hz to 10kHz. The amplitude of the incus vibration was found to be in the range between 10pm to 100nm, strongly depending on the frequency, with a lot of resonant peaks, corresponding mainly to the natural outer ear canal gain. The noise floor in the experiments was about 2pm/Hz1/2, but recently we have decreased it to < 0.5pm/Hz1/2, which corresponds to a minimal detectable sound level of 31-35dB(A) SPL for humans. The histological examination of temporal bones of cadaver animals and the intensity of in-vivo optical signal demonstrated that the aiming of the sensing fiber to the target has been preserved for five months after the implantation.
Multicore and microstructured fibers open a new door for designing all-fiber telecom components. In this article we propose a design of an optical power splitter based on the phenomenon of power coupling in the tapered splice between a single-core (SMF-28) and a seven core fiber (MCF-7), which was originally developed for spatial division multiplexing telecommunication systems. Comprehensive numerical analysis is presented and backed up with an experimental demonstration.
Cancer is the second largest disease throughout the world with an increasing mortality rate over the past few years. The patient's survival rate is uncertain due to the limitations of cancer diagnosis and therapy. Early diagnosis of cancer is decisive for its successful treatment. A biomarker-based cancer diagnosis may significantly improve the early diagnosis and subsequent treatment. Biosensors play a crucial role in the detection of biomarkers as they are easy to use, portable, and can do analysis in real time. This review describes various biosensors designed for detecting nucleic acid and protein-based cancer biomarkers for cancer diagnosis. It mainly lays emphasis on different approaches to use electrochemical, optical, and mass-based transduction systems in cancer biomarker detection. It also highlights the analytical performances of various biosensor designs concerning cancer biomarkers in detail.
Spontaneous bacterial peritonitis is an acute bacterial infection of ascitic fluid; it has a high incidence in cirrhotic patients and it is associated with high mortality. In such a situation, early diagnosis and treatment is crucial for the survival of the patient. However, bacterial analysis in ascitic fluid is currently based on culture methods, which are time-consuming and laborious. We report here the application of a photonic interferometer biosensor based on a bimodal waveguide (BiMW) for the rapid and label-free detection of bacteria directly in ascitic fluid. The device consists of a straight waveguide in which two modes of the same polarization interfere while interacting with the external medium through their evanescent fields. A bimolecular event occurring on the sensor area of the device (e.g. capturing bacteria) will differently affect each light mode, inducing a variation in the phase of the light exiting at the output of the waveguide. In this work, we demonstrate the quantitative detection of Bacillus cereus in buffer medium and Escherichia coli in undiluted ascitic fluid from cirrhotic patients. In the case of Bacillus cereus detection, the device was able to specifically detect bacteria at relevant concentrations in 12.5 min and in the case of Escherichia coli detection, the analysis time was 25 min. Extrapolation of the data demonstrated that the detection limits of the biosensor could reach few bacteria per milliliter. Based on the results obtained, we consider that the BiMW biosensor is positioned as a promising new clinical tool for user-friendly, cost-effective and real-time microbiological analysis.
Epidermal growth factor receptor (EGFR) is a non-small-cell lung cancer biomarker, based on which several near-patient-testing methods have been developed and applied to predict treatment response on individual patients. Existing methods for detection of EGFR mutation are costly, labor-intensive and time-consuming. In this paper, we report a novel EGFR mutation testing system, which is based on Mach-Zehnder Interferometer (MZI) sensor and isothermal solid-phase DNA amplification (IDA) technique, called MZI-IDA sensor system. The system can deliver results within 30min and shows high sensitivity to detect trace amounts of genomic DNA (<1 copy). In addition, the system is able to detect a L858R mutation in a 99:1 mixture of wild-type and mutant cells. In a pilot clinical study, the system is compared with conventional methods (PCR and direct sequencing) by using tissue biopsy samples from NSCLC patients. The MZI-IDA sensor system is proved to be capable of fast and accurate detection of the L858R mutation of EGFR gene in clinical samples. This may greatly help the clinicians develop an appropriate treatment plan.
Copyright © 2015 Elsevier B.V. All rights reserved.
MicroRNAs have been identified as promising biomarkers for human diseases. The development of a point-of-care (POC) test for the disease-associated miRNAs would be especially beneficial, since miRNAs are unexpectedly well preserved in various human specimens, including urine. Here, we present the Mach-Zehnder interferometer-miRNA detection system capable of detecting multiple miRNAs in clinical urine samples rapidly and simultaneously in a label-free and real-time manner. Through measurement of the light phase change, the MZI sensor provides an optical platform for fast profiling of small molecules with improved accuracy. We demonstrate that this system could specifically detect target miRNAs (miR-21, and let-7a), and even identify the single nucleotide polymorphism of the let-7 family of miRNAs from synthetic and cell line samples. The clinical applicability of this system is confirmed by simultaneously detecting two types of miRNAs in urine samples of bladder cancer patients in a single reaction, with a detection time of 15min. The POC system can be expanded to detect a number of miRNAs of different species and should be useful for a variety of clinical applications requiring at or near the site of patient care.
Copyright © 2015 Elsevier B.V. All rights reserved.
Integrated planar optical waveguide interferometer biosensors are advantageous combinations of evanescent field sensing and optical phase difference measurement methods. By probing the near surface region of a sensor area with the evanescent field, any change of the refractive index of the probed volume induces a phase shift of the guided mode compared to a reference field typically of a mode propagating through the reference arm of the same waveguide structure. The interfering fields of these modes produce an interference signal detected at the sensor׳s output, whose alteration is proportional to the refractive index change. This signal can be recorded, processed and related to e.g. the concentration of an analyte in the solution of interest. Although this sensing principle is relatively simple, studies about integrated planar optical waveguide interferometer biosensors can mostly be found in the literature covering the past twenty years. During these two decades, several members of this sensor family have been introduced, which have remarkably advantageous properties. These entail label-free and non-destructive detection, outstandingly good sensitivity and detection limit, cost-effective and simple production, ability of multiplexing and miniaturization. Furthermore, these properties lead to low reagent consumption, short analysis time and open prospects for point-of-care applications. The present review collects the most relevant developments of the past twenty years categorizing them into two main groups, such as common- and double path waveguide interferometers. In addition, it tries to maintain the historical order as it is possible and it compares the diverse sensor designs in order to reveal not only the development of this field in time, but to contrast the advantages and disadvantages of the different approaches and sensor families, as well.
In a recent study, we reported for the first time the detection of a model protein Bovine Serum Albumin (BSA) using antibody-immobilized tapered fiber optic biosensors (TFOBS) at 1550nm under stagnant condition, with a detection limit of 10fg/mL. In this study, we examine the detection of BSA in a flow cell configuration because flow reduces non-specific adsorption of contaminating proteins, eliminates transmission changes due to mechanical movements, and allows for quick switching between samples.TFOBS were fabricated with waist diameters of 5–10μm and total lengths of 1000–1200μm. They were housed in a specially constructed holder which served as a flow cell. The non-specific response of the TFOBS was measured by flowing in aqueous glucose solutions of various refractive indices at 0.5mL/min. Detection experiments were conducted by immobilizing antibody to BSA on TFOBS surface, and then exposing them to 1pg/mL–10ng/mL of BSA at 0.5mL/min and measuring the transmission at 1310nm and 1550nm. In addition, 1pg/mL of BSA in the presence of 1pg/mL of Ovalbumin (OVA) was measured successfully in the same apparatus.The transmission of TFOBS is a function of refractive index of the liquid surrounding the taper, and depends on the wavelength. Both pure BSA and BSA in the presence of OVA were detected in the flow cell arrangement. The transmission response and attachment rates were quantified and found to be similar for the two cases.
Microscale regenerable biosensors are described and utilized to measure the natural fluorophor benzo[a]pyrene tetraol (BPT). The sensors combine laser-excited/fiber-optic remote sensing principles with a unique capillary tube delivery system to make repetitive, heterogeneous fluoroimmunoassay measurements. Two sensor configurations and modes of operation are described. Concentrations of BPT in the nanomolar range are easily measured with a reproducibility of 10% or better, depending on the sensor design, selective measurements can be made in ca. 20 min, then the sensor can be regenerated by delivering new reagents to the sensing chamber, without removing the sensor from the sample.
An Escherichia coli strain, genetically modified to emit a luminescent signal in the presence of genotoxic agents, was alginate-immobilized onto an exposed core of a fiber-optic. The performance of this whole-cell optical fiber sensor system was examined as a function of several parameters, including gel probe matrix volume, bacterial cell density, numerical aperture of the fiber core and working temperature. An optimal response to a model genotoxicant, mitomycin C, was achieved with six alginate/bacterial adlayers on a 1 cm exposed fiber-optic core. Total alginate volume per tip was about 100 ml, containing a bacterial suspension of around 1.5–3:0 Â 10 7 cells. When the core diameter was etched down to 270 mm, photon detection efficiency significantly increased, although to a lesser extent than that expected from theoretical calculations. Further reduction in core diameter led to a reduced performance. Activity at 378C was superior to that at 268C. Under these optimized conditions, optrode response was mitomycin C dose-dependent for at least 6 h, with a lower detection threshold of 25 mg/l. # 2001 Elsevier Science B.V. All rights reserved.