Multiplexed detection of cancer biomarkers using an optical biosensor

Early detection of cancer is important in administering timely treatment and increasing cancer survival rates. For early cancer detection one can use biomarkers, which are characteristics that can be objectively measured or evaluated as indicators of normal or pathogenic processes. In our study we study three protein biomarkers: carcinoembryonic antigen (CEA), interleukin-6 (IL-6) and extracellular protein kinase A (ECPKA), which have been implicated in various types of human cancer. The main objective of this project is to develop a biosensor for detection of multiple cancer biomarkers. To detect these protein biomarkers high affinity ssDNA aptamers are being selected. Aptamers are short single stranded DNAs with an ability to bind to various targets with high affinity and specificity which selected by SELEX (Systemic Evolution of Ligands through Exponential enrichment) [2]. Ultimately, aptamers against each of the biomarker will be conjugated to magnetic nanoparticles to capture biomarkers from biological fluids. Another aptamer is proposed to be conjugated to quantum dots for quantitation of biomarkers when analyzed on spectrometer

Multiplexed detection of cancer biomarkers using an optical biosensor

Early detection of cancer is important in administering timely treatment and increasing cancer survival rates. For early cancer detection one can use biomarkers, which are characteristics that can be objectively measured or evaluated as indicators of normal or pathogenic processes. In our study we study three protein biomarkers: carcinoembryonic antigen (CEA), interleukin-6 (IL-6) and extracellular protein kinase A (ECPKA), which have been implicated in various types of human cancer. The main objective of this project is to develop a biosensor for detection of multiple cancer biomarkers. To detect these protein biomarkers high affinity ssDNA aptamers are being selected. Aptamers are short single stranded DNAs with an ability to bind to various targets with high affinity and specificity which selected by SELEX (Systemic Evolution of Ligands through Exponential enrichment) [2]. Ultimately, aptamers against each of the biomarker will be conjugated to magnetic nanoparticles to capture biomarkers from biological fluids. Another aptamer is proposed to be conjugated to quantum dots for quantitation of biomarkers when analyzed on spectrometer

Fiber bragg gratings for medical applications and future challenges: A review

In the last decades, fiber Bragg gratings (FBGs) have become increasingly attractive to medical applications due to their unique properties such as small size, biocompatibility, immunity to electromagnetic interferences, high sensitivity and multiplexing capability. FBGs have been employed in the development of surgical tools, assistive devices, wearables, and biosensors, showing great potentialities for medical uses. This paper reviews the FBG-based measuring systems, their principle of work, and their applications in medicine and healthcare. Particular attention is given to sensing solutions for biomechanics, minimally invasive surgery, physiological monitoring, and medical biosensing. Strengths, weaknesses, open challenges, and future trends are also discussed to highlight how FBGs can meet the demands of next-generation medical devices and healthcare system

Perspectives on Assembling Coronavirus Spikes on Fiber Optics to Reveal Broadly Recognizing Antibodies and Generate a Universal Coronavirus Detector

In time of COVID-19 biological detection technologies are of crucial relevance. We propose here the use of state of the art optical fiber biosensors to address two aspects of the fight against SARS-CoV-2 and other pandemic human coronaviruses (HCoVs). Fiber optic biosensors functionalized with HCoV spikes could be used to discover broadly neutralizing antibodies (bnAbs) effective against known HCoVs (SARS-CoV, MERS-CoV and SARS-CoV-2) and likely future ones. In turn, identified bnAbs, once immobilized onto fiber optic biosensors, should be capable to detect HCoVs as diagnostic and environmental sensing devices. The therapeutic and preventative value of bnAbs is immense as they can be used for passive immunization and for the educated development of a universal vaccine (active immunization). Hence, HCoV bnAbs represent an extremely important resource for future preparedness against coronavirus-borne pandemics. Furthermore, the assembly of bnAb-based biosensors constitutes an innovative approach to counteract public health threats, as it bears diagnostic competence additional to environmental detection of a range of pandemic strains. This concept can be extended to different pandemic viruses, as well as bio-warfare threats that entail existing, emerging and extinct viruses (e.g., the smallpox-causing Variola virus). We report here the forefront fiber optic biosensor technology that could be implemented to achieve these aims

Picomolar detection of thrombin with fiber-optic ball resonator sensor using optical backscatter reflectometry

A ball resonator, positioned on the tip of an optical fiber, has been developed as a biosensor for the prototypic detection of thrombin. The device was fabricated with a fast and repeatable CO2 laser splicing method, followed by gold-sputtering and functionalization for the measurement of various protein concentrations. The ball resonator acts as a weak interferometer with a return loss below − 50 dB, and it is interrogated with an optical backscatter reflectometer measuring the reflection spectrum. We report here a sample presenting high sensitivity (1273.74 nm/RIU, RIU = refractive index units), which allows protein detection in the range 0.4–100 pM, with a limit of detection of 1.56 pM in logarithmic response

Ultralow Limit Detection of Soluble HER2 Biomarker in Serum with a Fiber-Optic Ball-Tip Resonator Assisted by a Tilted FBG

An optical-fiber biosensor has been developed for the detection of the breast cancer biomarker soluble human epidermal growth factor receptor-2 (sHER2). The sensor was fabricated by combining a tilted fiber Bragg grating (TFBG) with a ball resonator, allowing us to achieve an excellent sensitivity compared to other optical-fiber-based sensors. The sensor exhibits a resonance comb excited by the TFBG and the spectral profile of the ball resonator. The detection of sHER2 at extremely low concentrations was carried out by tracking the amplitude change of selected resonances. The therapeutic anti-HER2 monoclonal antibody Trastuzumab has been used to functionalize the biosensor with silane surface chemistry. The sensor features a sensitivity of 4034 dB/RIU with a limit of detection (LoD) in buffer and in a 1/10 diluted serum of 151.5 ag/mL and 3.7 pg/mL, respectively. At relatively high protein concentrations (64 ng/mL) binding to sHER (7.36 dB) as compared to control proteins (below 0.7 dB) attested the high specificity of sHER2 detection

Functionalized etched tilted fiber Bragg grating aptasensor for label-free protein detection

An aptasensor based on etched tilted fiber Bragg grating (eTFBG) is developed on a single-mode optical fiber targeting biomolecule detection. TFBGs were chemically etched using hydrofluoric acid (HF) to partially remove the fiber cladding. The sensor response was coarsely interrogated, resulting on a sensitivity increase from 1.25 nm/RIU (refractive index unit) at the beginning of the process, up to 23.38 nm/RIU at the end of the etching, for a RI range from 1.3418 to 1.4419 RIU. The proposed aptasensor showed improved RI sensitivity as compared to the unetched TFBG, without requiring metal depositions on the fiber surface or polarization control during the measurements. The proposed sensor was tested for the detection of thrombin-aptamer interactions based on silane-coupling surface chemistry, with thrombin concentrations ranging from 2.5 to 40 nM. Functionalized eTFBGs provided a competitive platform for biochemical interaction measurements, showing sensitivity values ranging from 2.3 to 3.3 p.m./nM for the particular case of thrombin detection

Development of an optical biosensor for diagnosis of tuberculosis

Tuberculosis (TB) is an airborne disease caused by Mycobacterium tuberculosis. TB is the leading cause of morbidity and mortality in the developing world. Early and accurate diagnosis of TB would greatly enhance the treatment and prevention of the disease. Current methods of TB detection suffer from various limitations such as low specificity and sensitivity, being too complex and expensive. In the present work, we aim to develop an optical biosensor based on DNA aptamers, quantum dot (QD) crystals and magnetic nanoparticles (MNP) for detection of MPT64 protein, specific to M.tuberculosis. Aptamer-MNP conjugate is used for separation of MPT64 from solution, while aptamer-QD is used to detect its presence afterwards using fluorometer