Laser Biosensor Research Articles

Ultrasensitive detection of SCCA employing a graphene oxide integrated microfiber ring laser biosensor

Squamous cell carcinoma antigen (SCCA) is one of the most commonly detected cancer biomarkers for a variety of cancers. In this paper, a microfiber ring laser biosensor with a graphene oxide linking layer for SCCA detection was proposed and experimentally demonstrated. SCCA antibody immobilized on graphene oxide surface binds specifically to SCCA, and induces refractive index variation over the surface of the microfiber biosensor, which leads to a wavelength shift of the microfiber ring laser biosensor. The experimental results show that the proposed laser biosensor can detect SCCA with concentrations from 0.01 to 50 ng/mL, and the calculated detection limit can be as low as 1.3 pg/mL. Additionally, the label-free quantitative detection of SCCA using the proposed microfiber biosensor was verified experimentally according to the corresponding regression equation, and the results agree well with clinical examination detection. This constructed microfiber biosensor may have promising practical applications in analytical detection, medical diagnostics, etc.

Magnetic microspheres enhanced peanut structure cascaded lasso shaped fiber laser biosensor for cancer marker-CEACAM5 detection in serum

The detection of trace cancer markers in body fluids such as blood/serum is crucial for cancer diseases screening and treatment, which requires high sensitivity and specificity of biosensors. In this study, a peanut structure cascaded lasso (PSCL) shaped fiber sensing probe based on fiber laser demodulation method was proposed to specifically detect the carcinoembryonic antigen related cell adhesion molecules 5 (CEACAM5) protein in serum. Thanks for the narrow linewidth and high signal-to-noise ratio (SNR) of the laser spectrum, it is easier to distinguish small spectral changes than interference spectrum. Adding the antibody modified magnetic microspheres (MMS) to form the sandwich structure of "antibody-antigen-antibody-MMS", and amplified the response caused by biomolecular binding. The limit of detection (LOD) for CEACAM5 in buffer could reach 0.11 ng/mL. Considering the common threshold of 5 ng/mL for CEA during medical screening and the cut off limit of 2.5 ng/mL for some kits, the LOD of proposed biosensor meets the actual needs. Human serum samples from a hospital were used to validate the real sensing capability of proposed biosensor. The deviation between the measured value in various serum samples and the clinical value ranged from 1.9 to 9.8 %. This sensing scheme holds great potential to serve as a point of care testing (POCT) device and extend to more biosensing applications.

Fiber Laser-Based Lasso-Shaped Biosensor for High Precision Detection of Cancer Biomarker-CEACAM5 in Serum.

Detection of trace tumor markers in blood/serum is essential for the early screening and prognosis of cancer diseases, which requires high sensitivity and specificity of the assays and biosensors. A variety of label-free optical fiber-based biosensors has been developed and yielded great opportunities for Point-of-Care Testing (POCT) of cancer biomarkers. The fiber biosensor, however, suffers from a compromise between the responsivity and stability of the sensing signal, which would deteriorate the sensing performance. In addition, the sophistication of sensor preparation hinders the reproduction and scale-up fabrication. To address these issues, in this study, a straightforward lasso-shaped fiber laser biosensor was proposed for the specific determination of carcinoembryonic antigen (CEA)-related cell adhesion molecules 5 (CEACAM5) protein in serum. Due to the ultra-narrow linewidth of the laser, a very small variation of lasing signal caused by biomolecular bonding can be clearly distinguished via high-resolution spectral analysis. The limit of detection (LOD) of the proposed biosensor could reach 9.6 ng/mL according to the buffer test. The sensing capability was further validated by a human serum-based cancer diagnosis trial, enabling great potential for clinical use. The high reproduction of fabrication allowed the mass production of the sensor and extended its utility to a broader biosensing field.

Biosensing with free space whispering gallery mode microlasers

Highly accurate biosensors for few or single molecule detection play a central role in numerous key fields, such as healthcare and environmental monitoring. In the last decade, laser biosensors have been investigated as proofs of concept, and several technologies have been proposed. We here propose a demonstration of polymeric whispering gallery microlasers as biosensors for detecting small amounts of proteins, down to 400 pg. They have the advantage of working in free space without any need for waveguiding for input excitation or output signal detection. The photonic microsensors can be easily patterned on microscope slides and operate in air and solution. We estimate the limit of detection up to 148 nm/RIU for three different protein dispersions. In addition, the sensing ability of passive spherical resonators in the presence of dielectric nanoparticles that mimic proteins is described by massive ab initio numerical simulations.

A label-free fiber ring laser biosensor for ultrahigh sensitivity detection of Salmonella Typhimurium

The rapid detection of low concentrations of Salmonella Typhimurium (S. Typhimurium) is an essential preventive measure for food safety and prevention of foodborne illness. The study presented in this paper addresses this critical issue by proposing a single mode-tapered seven core-single mode (STSS) fiber ring laser (FRL) biosensor for S. Typhimurium detection. The experimental results show that the specific detection time of S. Typhimurium is less than 20 min and the wavelength shift can achieve −0.906 nm for an S. Typhimurium solution (10 cells/mL). Furthermore, at a lower concentration of 1 cell/mL applied to the biosensor, a result of −0.183 nm is observed in 9% of samples (1/11), which indicates that the proposed FRL biosensor has the ability to detect 1 cell/mL of S. Typhimurium. In addition, the detection results in chicken and pickled pork samples present an average deviation of −27% and −23%, respectively, from the measured results in phosphate buffered saline. Taken together, these results show the proposed FRL biosensor may have potential applications in the fields of food safety monitoring, medical diagnostics, etc.

Ultrahigh-sensitivity label-free singlemode- tapered no core-singlemode fiber immunosensor for Listeria monocytogenes detection

A challenge for optical fiber biosensor is to achieve ultrahigh sensitivity with narrow full width at half maximum (FWHM) of the spectrum. To address this challenge, an ultrahigh-sensitivity microfiber interferometer fiber ring laser (FRL) biosensor is proposed and investigated for Listeria monocytogenes (L. monocytogenes) detection. The fiber biosensor is composed of a singlemode- tapered no core-singlemode (STNS) fiber configuration, which is functionalized with the anti-L. monocytogenes antibodies. An Erbium Doped Fiber Amplifier is applied to the sensor to excite laser and thus reduce the FWHM of the spectrum, which significantly improved the limit of detection (LoD). The proposed STNS FRL biosensor has excellent reproducibility, specificity and sensitivity for L. monocytogenes. The developed STNS FRL biosensor can directly detect L. monocytogenes cells with LoD as low as 1.0 cell/mL, indicating the capability for detecting single cell of L. monocytogenes. Real lettuce and milk samples have been tested and test result in lettuce and milk samples has deviations within ± 30 % from that of Phosphate-buffered saline (PBS) for L. monocytogenes concentrations vary from 101 to 103 cells/mL(g). The developed STNS FRL biosensor has ultrahigh sensitivity, good stability, reproducibility, and specificity, which has potential applications in diseases/medical diagnostics.

Laser-scribed graphene nanofiber decorated with oil palm lignin capped silver nanoparticles: a green biosensor

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tuberculosis), requires a high level of attention and is one of the most infectious diseases in the air. Present methods of diagnosing TB remain ineffective owing to their low sensitivity and time consumption. In this study, we produced a green graphene nanofiber laser biosensor (LSG-NF) decorated with oil palm lignin-based synthetic silver nanoparticles (AgNPs). The resulting composite morphology was observed by field-emission scanning electron microscopy and transmission electron microscopy, which revealed the effective adaptation of the AgNPs to the LSG-NF surface. The successful attachment of AgNPs and LSG-NFs was also evident from X-ray diffraction and Raman spectroscopy studies. In order to verify the sensing efficiency, a selective DNA sample captured on AgNPs was investigated for specific binding with M.tb target DNA through selective hybridisation and mismatch analysis. Electrochemical impedance studies further confirmed sensitive detection of up to 1 fM, where a detection limit of 10−15 M was obtained by estimating the signal-to-noise ratio (S/N = 3:1) as 3σ. Successful DNA immobilisation and hybridisation was confirmed by the detection of phosphorus and nitrogen peaks based on X-ray photoelectron spectroscopy and Fourier-transform infrared spectroscopy. The stability and repeatability of the analysis were high. This approach provides an affordable potential sensing system for the determination of M. tuberculosis biomarker and thus provides a new direction in medical diagnosis.

Development and analysis of surface plasmon resonance based refractive index sensor for pregnancy testing

In the proposed work, a two-dimensional photonic crystal fiber (PCF) based on the surface plasmon resonance (SPR) refractive index sensor has been demonstrated and designed which is so much helpful to gain a better sensitivity response in urine observation. In order to detect the pregnancy, the simulation and analysis have been performed in both normal and pregnant urine with the effective refractive indices values of 1.335, 1.34, 1.342 and 1.343 within the range of working wavelength from 1.75 µm to 2 µm. From this testing sensor, the optical parameters of the dispersion relation, birefringence, coupling length, confinement loss, insertion loss, sensor length, crosstalk, sensitivity response, resonance wavelength, resolution, and sensitivity per line-width have been analyzed. Besides, Finite element method (FEM) is used for the numerical investigations. From this investigation, the highest value of sensitivity response, sensitivity per line-width, and the resolution of 68051.344 nm/RIU, 314 RIU−1, and 9.39 × 10−6 RIU are gained. It is noted that the proposed sensor offers significant sensing performances for the polarized modes. The main goal of this investigation is to develop the concepts of optoelectronics and laser bio-sensor in the field of biological detection systems. As a result, this structure of optical biosensor will be applicable through the modified optical fiber in biological changes.

Hyperboloid-Drum Microdisk Laser Biosensors for Ultrasensitive Detection of Human IgG.

Whispering gallery mode (WGM) microresonators have been used as optical sensors in fundamental research and practical applications. The majority of WGM sensors are passive resonators that require complex systems, thereby limiting their practicality. Active resonators enable the remote excitation and collection of WGM-modulated fluorescence spectra, without requiring complex systems, and can be used as alternatives to passive microresonators. This paper demonstrates an active microresonator, which is a microdisk laser in a hyperboloid-drum (HD) shape. The HD microdisk lasers are a combination of a rhodamine B-doped photoresist and a silica microdisk. These HD microdisk lasers can be utilized for the detection of label-free biomolecules. The biomolecule concentration can be as low as 1 ag mL-1 , whereas the theoretical detection limit of the biosensor for human IgG in phosphate buffer saline is 9 ag mL-1 (0.06 aM ). Additionally, the biosensors are able to detect biomolecules in an artificial serum, with a theoretical detection limit of 9 ag mL-1 (0.06 aM ). These results are approximately four orders of magnitude more sensitive than those for the typical active WGM biosensors. The proposed HD microdisk laser biosensors show enormous detection potential for biomarkers in protein secretions or body fluids.

Nanomaterial-Enhanced Fiber Optofluidic Laser Biosensor for Sensitive Enzyme Detection

A novel fiber optofluidic laser biosensor based on nanoparticle-functionalized thin-walled hollow optical fiber is developed for sensitive detection of enzyme horseradish peroxidase (HRP). High sensitivity is achieved thanks to the high surface-to-volume ratio of the nanomaterials. Two kinds of attractive nanomaterials, i.e., Au nanorods and SiO2 nanoparticles, are selected as demonstrative models to be coated onto the inner surface of thin-walled hollow fiber through electrostatic adsorption and biochemical cross-linking, respectively, while the streptavidin-biotin conjugation mechanism acts as a bridge for the specific recognition of enzyme. The nanoparticle-functionalized fiber optofluidic lasers have lower lasing threshold, compared to the control group without nanomaterial. We experimentally demonstrate that the nanomaterials enhanced fiber optofluidic laser biosensors can detect HRP in the range of 75–15 000 pM with a good linearity in semi-logarithmic scale, and with a sensitivity enhancement of 57.4% by using the SiO2 nanoparticles. We believe that this nanoparticle-enhanced fiber optofluidic laser biosensor could provide an efficient strategy for biomolecule detection such as enzyme-linked immunosorbent assay (ELISA).

The Use of Sensor Models for Solving Egineering Problems in Livestock

Biosensor technologies is an interdisciplinary science related to the development of biological and information sciences, based on the creation of devices with biocomputing components forming neural network structures, also used for the identification of animals. (Research purpose) The aim of the study is studying and structuring information on the use of biosensor devices and systems in livestock, find the possibilities for subsequent introduction into industry’s practice through effective engineering solutions of pattern recognition, adaptive management of animal behavior, etc. (Materials and methods) We have used methods of collection, study, systematization, analysis of scientific information obtained from livestock practices, expert assessments made in accordance with the technological regulations of the scientific-and- technical funds, patent and license sources, innovative developments of leading manufacturers of machinery and equipment for the beef cattle identification. (Results and discussion) Theory and practice of biosensor science in animal-based biomedical research proved that a balanced, workable system of biosensor control reaches the value of 1,0 e10 - 1,0 e12 of individual cells-sensors. The pulse time of the neuron of 2-5 milliseconds is enough for evaluation of the animal’s habitus, as well as speed of movement, body temperature. It is possible to determine information about the physiological condition of the animal: rut, fatness, location or identity of animal, quality of sperm, embryos, authenticity of origin and other parameters on selected DNA samples by using smart laser and ultrasonic biosensors that transmit these data to smart chips. The article shows that the linear biological parameters of the object obtained with the sensors can be converted by calculation into nonlinear ones, with further telemetry transmission of information to the animal’s biochip and stationary receiving software device. Biocalculation devices are able to calculate and control the change in live weight of animals of different breeds up to 6 months of age, adjusted for the variability of the trait. It was found that the coefficient of variation Cv reaches 1.5-2.5 percent, and as the animal grows, it reaches of 15-18 percent. (Conclusion) The solution of engineering problems in animal husbandry with the help of biosensors and sensors of a new generation depends on the biochemical nature of the recognition element (its action algorithm can be calculated). Biocomputing devices are capable not only to accept, but also to count and to control various parameters of animals. The use of engineering biosensor intelligent systems and neurocybernetic in animal husbandry expands the possibilities of the industry, makes them attractive to the manufacturer and gives a great economic effect.

Size-dependent nonlinear optical properties of atomically thin PtS2 nanosheet

To manipulate the nonlinear optical absorption (NOA) properties of layered two dimensional (2D) materials by simple and cost-effective methods is an attractive research topic as the NOA properties can be further optimized for various potential applications, such as compact optical switchers, pulsed laser generation, optical limiters, and biosensors. In this work, the NOA response of the novel group 10 transition metal dichalcogenide (TMD), platinum disulfide (PtS2) is investigated with respect to different PtS2 flakes size and thickness for the first time. Four PtS2- NMP suspensions with modified size and thickness distribution were successfully fabricated. The average flake size and thickness ranged from about 565 nm to 110 nm and 30 nm–10 nm, respectively. Z-scan measurement shows that the NOA response of PtS2 depends heavily on the flake size and thickness. As the layer thickness and lateral size of the PtS2 nanosheets reduced, the widened bandgap and increased active nanosheet edges will facilitate the photon absorption and lead to an enhancement of the RSA effect. However, sustained elevation of the RSA effect will reach a saturation threshold, and the RSA response will become weaker afterwards. A variation of the NOA performance from an initial weakening of RSA response, and followed by switching to saturable absorption (SA) is observed in the Z-scan test as the flake size and thickness become lower from S3000 to S9000 PtS2 samples. This work has demonstrated a significant modification of NOA properties of the PtS2, which can further be utilized in various applications.

Evaluation and calculations of modes resonant cantilever for laser optical fiber assembly

<p>Biosensors depend on cantilevers have developed a promising tool for detecting biomedical, optical laser communication and many fields of interactions with high accuracy. We modeled the operation of cantilevers<strong> </strong>with two magnetic and coil using Ansys program. This simulation technique can capably be used to select the appropriate design and dimensions of cantilever with the geometry of system. The primary main of the magnetic design is to improve the geometry of the coil and shape to yield a highly uniform for 3D of optical fiber includes Silica Glass and Nickel cantilever, two magnets and one coil that apply to force on the cantilever cylinder is using as a cantilever in the designing of this case.In conclusion,resonant frequency( tuning applying cantilivier presented in the resracher have larger variable range by using 2-magnets with the coil.However,the adjusting of the system and changing the deminsions.Resolutions to this problematic contain tuning the modes of resonant frequency to produce by cantilivier with 2-magnets and coil when the signal pass from laser source. Based on these simulations and characterization results, the proposed assembly can be a good applicant for evolving a low price, high material platform for many biological, laser optical fiber, communication, machine learning, biosensors and biomedical applications.</p>

Design in line LMA-10 Photonic Crystal Fiber MZI for Detection and investigation of Beta Thalassemia

Consequent to the scarcity of removable rapid diagnostic examines for detecting the thalassemia, specially beta thalassemia trait or Cooly’s Anemia, present detection methods include the collection of the blood, which then required being more tests before reports can be made by the treating physicians.Traditional methods like hemoglobinopathy tests and blood picture are time expending, needing specialized technical personnel, extra huge and costly laboratory instrument. Here, we simulated and demonstrated micro- hole collapsing, type of Mazh-Zehnder interferometer (MZI) that formed using LMA-!0 fiber, with a laser beam for detection the most common type of anemia, beta thalassemia trait or Cooly’s Anemia .this interferometer made-up of two conventional optical fibers splicing to apart of photonic crystal fiber (PCF).this method makes a high sensitive regions for the optical characteristics in the blood sample. Biological changes in the blood sample consequent to the presence the beta thalassemia trait lead to changes optical characteristics (refractive index and absorption) of the blood sample the demonstrated laser biosensor has the ability for use as a removable, rapid diagnosis examines and the high sensitive which rises to 24.367 ABS/RIU

Design for Distributed Feedback Laser Biosensors Based on the Active Grating Model.

The distributed feedback (DFB) laser is widely used in sensing because of its portable size, simple fabrication and high sensitivity. Most theoretical design models are based on passive Bragg gratings. However, passive grating models cannot be used to predict sensor performance using the important indicator of figure of merit (FOM) through theoretical calculations. To solve this problem, we replaced the passive grating with an active grating by using the imaginary part of the coupling constant that represents the value of the gain. As a comparison, the influence of the full width at half maximum (FWHM) and sensitivity were analyzed for different grating duty cycles and depths in the passive grating sensors. To obtain a higher FOM in the active grating sensors, we systematically investigated the effects of duty cycle and gain value through numerical simulations. We found that the redshift caused by a duty cycle increase can improve the sensitivity of biomolecule detection by 1.7 times.

Laser biosensor use for the microbial metabolic activity assessment of kefir vinegar

Abstract: The objective of this work was to verify the use of a laser biosensor for the microbial metabolic activity assessment of kefir vinegar. Kefir grains were inoculated in apple must and were analyzed daily using the biospeckle technique. The initial biological activity was of 14.21 pixels per absolute value of differences (AVD). The biological activity of kefir grains decreased in the early days of fermentation and increased on the fourth day to 11.51 pixels per AVD; however, on the last day, the biological activity of kefir grains decreased to 7.12 pixels (alcoholic fermentation) and to 6.77 pixels per AVD (acetic fermentation). This new biospeckle methodology facilitates the microbiological control in fermentation processes.

The potential of naturally occurring lasing for biological and chemical sensors

Although recent advances in biosensing are promising, there still is a need for label-free, sensitive, and cost-effective detection of single nanoparticles and single biomolecules, without relying in complex fabrications and sophisticated detection strategies. In this review, we show that a better understanding of light-matter interactions can lead to the development of advanced biosensing and bioanalysis systems. In particular, we address alternative biosensing methods of taking advantage of naturally occurring lasers (also known as random lasers). In random lasers, resonances are self-formed due to multiple scattering, leading to light amplification and coherent light generation in the presence of amplifying media. In this case, lasing emission can be unprecedentedly sensitive to subtle nanoscale perturbations. Specifically, we discuss the possibility that random lasers can be an alternative yet superior physical mechanism for biosensors, because the random laser biosensing platform is simple and the detection strategy is straightforward. We further envision that random laser biosensors have the potential to facilitate developing enhanced biological and chemical sensors for single-molecule and single-nanoparticle quantitation.

Detection of protein-small molecule binding using a self-referencing external cavity laser biosensor.

High throughput screening of protein-small molecule binding interactions using label-free optical biosensors is challenging, as the detected signals are often similar in magnitude to experimental noise. Here, we describe a novel self-referencing external cavity laser (ECL) biosensor approach that achieves high resolution and high sensitivity, while eliminating thermal noise with sub-picometer wavelength accuracy. Using the self-referencing ECL biosensor, we demonstrate detection of binding between small molecules and a variety of immobilized protein targets with binding affinities or inhibition constants in the sub-nanomolar to low micromolar range. The demonstrated ability to perform detection in the presence of several interfering compounds opens the potential for increasing the throughput of the approach. As an example application, we performed a "needle-in-the-haystack" screen for inhibitors against carbonic anhydrase isozyme II (CA II), in which known inhibitors are clearly differentiated from inactive molecules within a compound library.

Distributed feedback laser for biosensing applications.

We present an organic semiconductor distributed feedback laser biosensor and demonstrate its sensing capabilities. Optimization of the gain layer thickness to maximize the response to refractive index changes and bulk sensing results are shown. Desthiobiotin-avidin sensing assay results are also presented and the potential to perform multiple, repeated sensing measurements is demonstrated.

Detection of Protein–Small Molecule Binding Using a Self-Referencing External Cavity Laser Biosensor

High-throughput screening has enabled the identification of small molecule modulators of important drug targets via well-established colorimetric or fluorimetric activity assays. However, existing methods to identify small molecule binders of nonenzymatic protein targets lack either the simplicity (e.g., require labeling one of the binding partners with a reporter) or throughput inherent in enzymatic assays widely used for HTS. Thus, there is intense interest in the development of high-throughput technologies for label-free detection of protein–small molecule interactions. Here we describe a novel self-referencing external cavity laser (ECL) biosensor approach that achieves high resolution and high sensitivity, while eliminating thermal noise with subpicometer wavelength accuracy. Using the self-referencing ECL biosensor, we demonstrate detection of binding between small molecules and a variety of immobilized protein targets, pairs that have binding affinities or inhibition constants ranging from subnanomolar to low micromolar. Finally, a “needle-in-the-haystack” screen for inhibitors against carbonic anhydrase isozyme II is performed, in which known inhibitors are clearly differentiated from inactive molecules within a compound library.