Label-free Detection Of Biomolecules Research Articles

Vertical gate cavity bulk-planar junctionless FET-based biosensor for label-free detection of biomolecules

In this paper, we propose a vertical gate bulk-planar junctionless field-effect transistor (VGC-BPJLFET)-based biosensor for the label-free detection of neutral and charged target biomolecules. The vertical gate structure exhibits better performance due to high gate controlability in the channel region, which improves the drain current of the device. The enhancement in drain current significantly increases the sensing capability of the biosensor. To sense the neutral (APTES, biotin, streptavidin, protein, etc) and charged (deoxyribonucleic acid (DNA)) target biomolecules, the VGC-BPJLFET biosensor includes a vertical nanogap cavity in between the gate electrodes of the device in which HfO2 behaves as the functionalization layer. However, for the detection of both neutral and charged biomolecules, the two electric parameters (dielectric constant (K) and the charge density (ρ)) are considered in the etched nanogap cavity. Furthermore, to see the potentiality of the VGC-BPJLFET biosensor, the proposed biosensor has been compared to the lateral gate cavity BPJLFET biosensor in terms of drain current, sensitivity, linearity and signal-to-noise ratio characteristics. From the comparison, it has been observed that the proposed device has a higher sensitivity of ∼104 and ∼103 with the conjugation of neutral (APTES (K = 3.57)) and charged (DNA (ρ = −1 × 1011 cm−2)) biomolecules, respectively. The VGC-BPJLFET biosensor also carries the better sensing capability to sense the target biomolecules with the presence of unwanted (air) biomolecules in the etched nanogap cavity.

Sensitivity Assessment of Electrically Doped Cavity on Source Junctionless Tunnel Field-Effect Transistor-Based Biosensor

The tunnel field-effect transistor (TFET) has emerged as a promising device for biosensing applications due to band-to-band tunneling (BTBT) operation mechanism and a steep subthreshold swing. In this paper, an electrically doped cavity on source junctionless tunnel field-effect transistor (ED-CS-JLTFET)-based biosensor is proposed for label-free detection of biomolecules. In the proposed model, the electrically doped concept is enabled to reduce fabrication complexity and cost. In order to create a nano-cavity at the source region, some portion of the dielectric oxide of the polarity gate terminal is etched away. To perceive the presence of biomolecules, two important properties of biomolecules, such as dielectric constant and charge density, are incorporated throughout the simulation. The sensing performance of the proposed ED-CS-JLTFET-based biosensor has been analyzed in terms of transfer characteristics, threshold voltage and subthreshold swing. In addition, the sensitivity of the proposed biosensor has also been analyzed with respect to different fill factors (FFs), varying nano-cavity dimension and work-function of the control gate. It is found from the simulated results that the proposed ED-CS-JLTFET-based biosensor offers higher current sensitivities with neutral, positively charged and negatively charged biomolecules of [Formula: see text] (at k [Formula: see text]), [Formula: see text] (at [Formula: see text] and [Formula: see text] C[Formula: see text]cm[Formula: see text]) and [Formula: see text] (at k [Formula: see text] and [Formula: see text] C[Formula: see text]cm[Formula: see text]), respectively.

Wafer-Scale LSPR Substrate: Oblique Deposition of Gold on a Patterned Sapphire Substrate.

Label-free detection of biomolecules using localized surface plasmon resonance (LSPR) substrates is a highly attractive method for point-of-care (POC) testing. One of the remaining challenges to developing LSPR-based POC devices is to fabricate the LSPR substrates with large-scale, reproducible, and high-throughput. Herein, a fabrication strategy for wafer-scale LSPR substrates is demonstrated using reproducible, high-throughput techniques, such as nanoimprint lithography, wet-etching, and thin film deposition. A transparent sapphire wafer, on which SiO2-nanodot hard masks were formed via nanoimprint lithography, was anisotropically etched by a mixed solution of H2SO4 and H3PO4, resulting in a patterned sapphire substrate (PSS). An LSPR substrate was finally fabricated by oblique deposition of Au onto the PSS, which was then applied to label-free detection of the binding events of biomolecules. To the best of our knowledge, this paper is the first report on the application of the PSS used as an LSPR template by obliquely depositing a metal.

Highly sensitive biosensor based on an all-dielectric asymmetric ring metasurface.

We propose an all-dielectric asymmetric ring-cylindrical metasurface. Based on the analysis of transmission characteristics and the calculation of electromagnetic field distribution of the metasurface with this element structure, it is found that the high Q resonance of the ultra-narrowband can be realized when the symmetry of the ring-cylindrical structure is broken. Meanwhile, it is found that the degree of asymmetry of the ring, the refractive index of the material, the radius of the ring, and the substrate have great influence on the Q value and resonant frequency of the metasurface. Our proposed metasurface structure is applied to the detection of biological molecules based on the change in refractive index of biomolecular solutions. The designed metasurface with high sensitivity to detect biomolecules with different refractive indices, the Q value can reach 365.03, and the sensitivity is increased by 90.36 GHz/RIU compared to that without substrate, while the figure of merit value is as high as 100.56, providing label-free detection of biomolecules.

Atomistic Simulations of Functionalized Nano-Materials for Biosensors Applications.

Nanoscale biosensors, a highly promising technique in clinical analysis, can provide sensitive yet label-free detection of biomolecules. The spatial and chemical specificity of the surface coverage, the proper immobilization of the bioreceptor as well as the underlying interfacial phenomena are crucial elements for optimizing the performance of a biosensor. Due to experimental limitations at the microscopic level, integrated cross-disciplinary approaches that combine in silico design with experimental measurements have the potential to present a powerful new paradigm that tackles the issue of developing novel biosensors. In some cases, computational studies can be seen as alternative approaches to assess the microscopic working mechanisms of biosensors. Nonetheless, the complex architecture of a biosensor, associated with the collective contribution from “substrate–receptor–analyte” conjugate in a solvent, often requires extensive atomistic simulations and systems of prohibitive size which need to be addressed. In silico studies of functionalized surfaces also require ad hoc force field parameterization, as existing force fields for biomolecules are usually unable to correctly describe the biomolecule/surface interface. Thus, the computational studies in this field are limited to date. In this review, we aim to introduce fundamental principles that govern the absorption of biomolecules onto functionalized nanomaterials and to report state-of-the-art computational strategies to rationally design nanoscale biosensors. A detailed account of available in silico strategies used to drive and/or optimize the synthesis of functionalized nanomaterials for biosensing will be presented. The insights will not only stimulate the field to rationally design functionalized nanomaterials with improved biosensing performance but also foster research on the required functionalization to improve biomolecule–surface complex formation as a whole.

Highly sensitive plasmonic nanorod hyperbolic metamaterial biosensor

Plasmonic sensing based on nanostructures is a powerful analytical tool for ultrasensitive label-free biomolecule detection that holds great potential in the field of clinical diagnostics and biomedical research. Here, we report the fabrication, the characterization, and the principle of operation of gold nanorod hyperbolic metamaterials (NHMMs) along with ultrasensitive bulk refractive index and label-free biomolecular detection. By combining electron-beam lithography and nanoscale electroplating, we demonstrate the fabrication of a highly ordered, height-controllable, and vertical array of nanorods. By exciting the bulk plasmon–polariton mode in the NHMM using a prism-coupling technique and integrating the sensor in microfluidics, we demonstrate that the bulk sensitivity and figure of merit of our device could reach 41,600 nm/RIU and 416 RIU-1, respectively. The physical mechanism of this high bulk sensitivity is revealed through theoretical and experimental studies. Moreover, by bio-functionalizing the surface of the NHMM sensor, monitoring the binding of streptavidin at dilute concentrations is performed in real time. We test different concentrations of streptavidin ranging from 200 to 5 µg/mL, and the NHMM biosensor exhibits a 1 nm wavelength shift for a 5 µg/mL streptavidin detection. By fitting the Hill equation of the NHMM biosensor and taking into account the level of noise (0.05 nm) as the minimum wavelength shift of the detectable limit, the limit of detection of the NHMM biosensor to streptavidin can be estimated to be 0.14 µg/mL (2.4 nm). As a direct comparison, a 0.5 nm wavelength shift for 20 µg/mL of streptavidin is reported when using a conventional gold film sensor under identical experimental conditions. The developed plasmonic NHMM sensor shows tremendous potential for highly sensitive bulk solutions and biomolecule detection and provides a promising avenue for free-label biosensing applications in the future.

Design and Investigation of Dielectrically Modulated Dual-Material Gate-Oxide-Stack Double-Gate TFET for Label-Free Detection of Biomolecules

This article investigates the applicability of dual-material gate-oxide-stack double-gate tunnel field effect transistor (DMGOSDG-TFET) as a biosensing element with the ability to assess the health parameters and disease onset. For this, employment of gate work-function engineering along with the gate-oxide-stack approach and asymmetrical doping at <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${p}^{+}$ </tex-math></inline-formula> source and <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${n}^{+}$ </tex-math></inline-formula> drain region are introduced for the first time to implement DMGOSDG-TFET-based biosensor. Also, a nanogap cavity is created by etching a portion of gate dielectric material toward the source end for the accomplishment of biomolecules conjugation in the proposed device. The main focus of this article is to estimate the underlying device sensitivity in the presence of different charged as well as neutral biomolecules. To explore such effects, different dielectric constants and negative charge densities of the biomolecules are considered independently in the nanogap cavity. Next, the sensing performance of the presented device is analyzed in terms of switching-ratio ( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${I}_{ \mathrm{\scriptscriptstyle ON}}/{I}_{ \mathrm{\scriptscriptstyle OFF}}$ </tex-math></inline-formula> ), transconductance-to-current ratio ( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${g}_{m}/{I}_{ds}$ </tex-math></inline-formula> ), and average subthreshold-swing. A deep investigation of device performance is also performed with different fillings of the nanogap cavity and step-profiles arising out from the steric hindrance. The device sensitivity is analyzed for different cavity lengths and cavity thicknesses for the best outcomes. In addition, a comparative sensitivity analysis of DMGOSDG-TFET with single-material gate-oxide-stack double-gate tunnel field effect transistor (SMGOSDG-TFET) and metal–oxide–semiconductor field effect transistor (MOSFET)-based biosensor is also presented in this work. The device implementation and all the simulations are carried out using technology computer-aided design (TCAD) tool. All of the sensitivity-assessments disclose that DMGOSDG-TFET can be a good candidate for biosensing applications.

Recent progress in silicon-based biologically sensitive field-effect devices

Biologically sensitive field-effect devices (BioFEDs) advantageously combine the electronic field-effect functionality with the (bio)chemical receptor's recognition ability for (bio)chemical sensing. In this review, basic and widely applied device concepts of silicon-based BioFEDs (ion-sensitive field-effect transistor, silicon nanowire transistor, electrolyte-insulator-semiconductor capacitor, and light-addressable potentiometric sensor) are presented, and recent progress (from 2019 to early 2021) is discussed. One of the main advantages of BioFEDs is the label-free sensing principle enabling them to detect a large variety of biomolecules and bioparticles by their intrinsic charge. The review encompasses applications of BioFEDs for the label-free electrical detection of clinically relevant protein biomarkers, DNA molecules and viruses, enzyme–substrate reactions as well as recording of the cell acidification rate (as an indicator of cellular metabolism) and the extracellular potential. • Biologically sensitive field-effect devices offer a universal platform for numerous (bio)chemical sensors. • Biologically sensitive field-effect devices enable label-free detection of biomolecules by their molecular charge. • Conventional device concepts are the ion-sensitive field-effect transistor, silicon nanowire field-effect transistor, electrolyte-insulator-semiconductor capacitor, and light-addressable potentiometric sensor. • Applications include detection of proteins, DNA, viruses, and cellular activity.

Noise immune dielectric modulated dual trench transparent gate engineered MOSFET as a label free biosensor: proposal and investigation.

We propose and investigate a biosensor based on a transparent dielectric-modulated dual-trench gate-engineered metal–oxide–semiconductor field-effect transistor (DM DT GE-MOSFET) for label-free detection of biomolecules with enhanced sensitivity and efficiency. Various sensing parameters such as the ION/IOFF ratio and the threshold voltage shift are evaluated as metrics to validate the proposed sensing device. Additionally, SVth (the Vth sensitivity) is also analyzed, considering both positively and negatively charged biomolecules. In addition, radiofrequency (RF) sensing parameters such as the transconductance gain and the cutoff frequency are taken into account to provide further insight into the sensitivity of the proposed device. Furthermore, the linearity, distortion, and noise immunity of the device are evaluated to confirm the overall performance of the biosensor at high (GHz) frequency. The results indicate that the proposed biosensor exhibits a SVth value of 0.68 for positively charged biomolecules at a very low drain bias of 0.2 V. The proposed device can thus be used as an alternative to conventional FET-based biosensors.

CMOS Biosensors for the Detection of DNA Hybridization in High Ionic-Strength Solutions

Label-free detection of biomolecules using ion-sensitive field-effect transistors (ISFETs) in physiological solutions is limited by the Debye charge-screening effect of the electrical double layer. Most ISFET measurements are therefore performed in diluted ionic-strength solutions to detect the interface potential change on specific binding of biomolecules. The novel CMOS ISFETs proposed in this study have a capacitor structure in the oscillator readout to provide modulation of the surface electric field to reduce the charge screening and nonideal signal drift. Signal modulation was applied at frequencies higher than the ion-strength-dependent cut-off frequency, with the highest applied frequency being approximately 100 MHz among the four proposed designs. The measured results revealed a pH sensitivity from 52.3 to 54.4 mV/pH in terms of the floating-gate potential change. Direct DNA hybridization in a high ionic-strength solution was successfully measured with a near picomolar-level resolution.

Analytical Model of Dielectric Modulated Trench Double Gate Junctionless FET for Biosensing Applications

A 2-D analytical model of a dielectric modulated trench double gate junctionless FET (DM-TDGJLFET) is developed for label-free detection of biomolecules. The channel potential is obtained by solving the 2-D Poisson's equation using the parabolic approximation with appropriate boundary conditions. The drain current and threshold voltage are obtained from the minimum channel potential. The proposed DM-TDGJLFET structure has two gates which are vertically placed in separate trenches. The two cavities for biomolecules immobilization are carved in the gate oxide region. The DM-TDGJLFET has been studied for threshold voltage sensitivityof neutral as well as charged biomolecules. For neutral biomolecules, the shift in threshold voltage is obtained as 745mV for change in dielectric constant (k) from 1 to 12. The DM-TDGJLFET performance is also evaluated using commercially available ATLASTM device simulator. The model results show good agreement with simulated data.

A Measurement Platform for Label-Free Detection of Biomolecules Based on a Novel Optical BioMEMS Sensor

In this article, a novel optical Bio-microelectromechanical system (MEMS) sensing platform is proposed based on a tunable laser and its lasing wavelength to detect the biomolecules and measure their quantities. The present biosensor consists of a BioMEMS cantilever and a proposed external cavity tunable laser. While the target samples (i.e., DNA, mRNA, or protein) are exposed to the cantilever surface, target-analyte bindings are happened. This can induce a surface stress on the MEMS cantilever and results in its bending due to the surface stress difference in each side of the cantilever. Thus, the gap size between the laser cavity and the gain medium is changed which can be measured by the wavelength variations of the proposed tunable laser source. Consequently, by analyzing the output response, one can detect the amount of target biomolecules in the sample and assign a level of contamination, infection, or bioparticles, caused by the specific disease. Various parameters of the proposed device are designed by numerical and analytical approaches. Furthermore, functional characteristics of the present BioMEMS sensor are obtained as follows: mechanical sensitivity of $1.8~\mu \text{m}$ /Nm−1, optical sensitivity of 422 nm/RIU, Q-factor of 610, and resonant frequency of 6.43 kHz. The obtained functional characteristics of the proposed device show that the present optical BioMEMS sensor can be appealing for highly sensitive diagnoses of various types of diseases and their progress level.

Comprehensive Understanding of Silicon-Nanowire Field-Effect Transistor Impedimetric Readout for Biomolecular Sensing.

Impedance sensing with silicon nanowire field-effect transistors (SiNW-FETs) shows considerable potential for label-free detection of biomolecules. With this technique, it might be possible to overcome the Debye-screening limitation, a major problem of the classical potentiometric readout. We employed an electronic circuit model in Simulation Program with Integrated Circuit Emphasis (SPICE) for SiNW-FETs to perform impedimetric measurements through SPICE simulations and quantitatively evaluate influences of various device parameters to the transfer function of the devices. Furthermore, we investigated how biomolecule binding to the surface of SiNW-FETs is influencing the impedance spectra. Based on mathematical analysis and simulation results, we proposed methods that could improve the impedimetric readout of SiNW-FET biosensors and make it more explicable.

Drain current characterization of dielectric modulated split gate TFET for bio-sensing application

This paper presents an analytical surface potential and drain current model of split gate (SG) Tunnel Field Effect Transistor (TFET) for label free detection of biomolecules e.g. protein, biotine, DNA, etc., utilizing the concept of underlap and dielectric modulation approach. A portion of the device channel is left open in between the splitted gates with a thin layer of silicon dioxide as adhesive layer. This open cavity acts as the binding site for the biomolecules to be detected which alters the effective capacitance of the region and hence modulates the device characteristic trend. The device electrostatics are developed by solving two dimensional Poisson’s equation and Young’s parabolic approximation and consequent drain current is then formulated applying Kane’s model. To assess the sensing ability of the device, both neutral and charged biomolecules with different dielectric values are immobilized within the cavity and the impact of variation in dielectric constant, charge density and height of biomolecules on device characteristics is analyzed. In addition to this, drain current sensitivity of the device is also investigated by varying the permittivity, charge density (both positive and negative) and height of the bio-species. All the analytical results are evaluated with corresponding Sentaurus TCAD simulated data to corroborate the accuracy of the derived model.

ZnO Nanorod FET Biosensors With Enhanced Sensing Performance: Design Issues for Rational Geometry Selection

ZnO nanorod field effect transistor (FET) biosensors enable ultrasensitive, rapid and label free detection of biomolecules. However, the fabrication of these nanorods without any design guideline results in poor signal to noise ratio, limiting their commercial deployment. The various forces operating within the spacing of the nanorods may prevent complete penetration of the liquid for large aspect ratios and hence mere enhancement of the geometric surface area may not yield the optimum output which indicates the intricacies involved in the design of such sensors. The present work consistently models the analyte and the device regions of the sensor by transforming the understanding of the transduction mechanism of biomolecule capture in nanowire FETs into nanorod FET structure and integrating the spacing dependent liquid penetration depth along with the various temporal fluctuations of the sensor to enhance the signal to noise ratio ( SNR ) and lower the molecule detection limit(MDL). Simulation results, verified experimentally for prostate specific antigen (PSA) shows that the optimal geometry does not correspond to the maximum surface area. Instead it is dependent on the developed surface potentials after receptor immobilization and ligand capture which vary non-monotonically with nanorod radius due to nonlinear dependence of buffer penetration for high aspect ratios. This approach has significantly increased the SNR leading to reliable quantification of PSA in human serum with MDL reduced by almost three orders of magnitude in comparison to recent reports. In summary, this work brings the ZnO nanorod sensors a step closer towards practical application for early diagnosis.

Simulation Study of Dielectric Modulated Dual Channel Trench Gate TFET-Based Biosensor

A dielectric modulated dual channel trench gate tunnel FET (DM-DCTGTFET) based biosensor is proposed for label-free detection of biomolecules. The gate of DM-DCTGTFET is placed vertically in a trench for creating two channels on both sides of the gate. The parallel conduction of two channels enhances the current of the DM-DCTGTFET. Further, in the proposed structure, two cavities are carved in the gate-oxide on either side of gate for biomolecules immobilization. The sensitivity performance of DM-DCTGTFET is analyzed using 2D simulations in the TCAD tool (ATLAS). The proposed structure exhibits high current sensitivity (~1012) as well as exorbitant voltage sensitivity ( $5.2 {V}$ ) which are significantly higher than the recently reported TFET based biosensors. Therefore, the DM-DCTGTFET biosensor is a highly promising structure due to dual sensing capabilities for biomolecules.

Signal Processing for Single Biomolecule Identification Using Nanopores: A Review

Nanopore sensors provide an innovative platform for rapid and label-free biomolecule detection. The analytical information extracted from resistive pulse sensing (RPS) measurement, though powerful has several limitations. To address these challenges, various signal conditioning algorithms have been researched which include efficient clustering and classification of data, applying probabilistic models to reduce information overlap and also leveraging transient analysis of ionic current instead of the steady state RPS measurement. Additionally, as the current is typically in few picoampere regime with high transition rates, its faithful measurement requires precision instrumentation like a patch clamp amplifier with low noise and high bandwidth. However, for practical deployment of such systems, it is necessary to develop portable electronic interface. Significant efforts have been directed globally to develop on-chip customized integrated circuits with low noise, high bandwidth amplifiers. Thus, it is absolutely timely and pertinent to conduct a review on the various signal processing schemes and electronic interfaces for single biomolecule identification using nanopores which will enable to comprehend the current status for its deployment as a commercial platform for genomics and ultrasensitive detection. To the best of our knowledge, the data extraction methodologies and electronic interface schemes for nanopores have not yet been summarized. In this paper, a comprehensive review emphasizing the signal processing algorithms for DNA sequencing and protein identification in complex analyte using functionalized and non-functionalized nanopores has been presented along with the on-chip low noise electronic interfaces required for field deployable measurement.

A Comprehensive Review on Tunnel Field-Effect Transistor (TFET) Based Biosensors: Recent Advances and Future Prospects on Device Structure and Sensitivity

In this fast-growing technological world biosensors become more substantial in human life and the extensive use of biosensors creates enormous research interest among researchers to define different approaches to detect biomolecules. The FET based biosensors have gained a lot of attention among all because of its high detection ability, low power, low cost, label-free detection of biomolecules, and CMOS compatible on-chip integration. The sensitivity of the biosensor inversely proportional to device size since they detect low concentration yields quick response time. Although FET based biosensor is having a lot of advantages among others but the short channel effects (SCE’s) and the theoretical limitation on the subthreshold swing (SS > 60mv/dec) of the FET leads to restrict device sensitivity and also have higher power dissipation due to the thermionic emission of electrons. To avoid these problems researchers focus shifts to the new technology FET based biosensors i.e. TFET based biosensors which are having low power and superior characteristics due to Band to band tunneling of carrier and steep subthreshold swing. This manuscript describes the full-fledged detail about the TFET based biosensors right from unfolding the device evaluation to biosensor application which includes qualitative and quantitative parameters analysis study like sensitivity parameters and different factors affecting the sensitivity by comparing different structures and the mechanisms involved. The manuscript also describes a brief review of different sensitivity parameters and improvement techniques. This manuscript will give researchers a brief idea for developing for the future generation TFET biosensors with better performance and ease of fabrication.

Extended Source Double-Gate Tunnel FET Based Biosensor with Dual Sensing Capabilities

An extended source double-gate tunnel FET (ESDG-DMTFET) based biosensor is proposed for label free detection of biomolecules. The proposed device consists of two parallel gates with source extended into the channel so that channel overlaps the source on both sides. The cavities are carved in the gate-oxide towards drain side in order to maximize the impact of change in dielectric constant of biomolecules on the source-channel tunnelling junction leading to substantial improvement in the performance of ESDG-DMTFET. Based on 2D simulations in TCAD simulator (ATLAS), the proposed biosensor is demonstrated to achieve two order of magnitude improvement in current sensitivity and eight times higher threshold voltage sensitivity as compared to reported TFET based biosensors.

Surface functionalized β-Bi2O3 nanofibers based flexible, field-effect transistor-biosensor (BioFET) for rapid, label-free detection of serotonin in biological fluids

In this work, we demonstrate a high-performance Field effect transistor-based biosensor (BioFET) on Al functionalized β-Bi2O3 nanofibers for highly selective and rapid detection of serotonin. The β-Bi2O3 nanofibers were synthesized using electrospinning technique and conductivity was tailored by surface functionalization using Al nanoparticles. Interdigitated silver electrodes deposited over the flexible polyimide (PI) substrate acts as contact terminals and dielectric substrate respectively while Al functionalized β-Bi2O3 nanofibers acts as n-type semiconductor channel and a thermally evaporated silver electrode beneath the PI tape as a back-gate terminal. Detailed characterization reveals the formation of β-phase monoclinic, high mobility, 1-D Bi2O3 nanofibers, and Al functionalization was validated using elemental composition studies. The fabricated FET exhibited a transconductance of 5.23 μS and mobility of 64.4 cm2 V−1s−1 with an Ion/ Ioff ratio ∼106. The BioFET exhibited an excellent sensitivity of 51.64 μA/nM towards serotonin over a wide linear detection range of 10 nM- 1 μM and a limit of detection of 0.29 nM. This can be ascribed to the excellent change in surface potential upon interaction of serotonin molecules with the electroactive surface functionalized multidimensional nanoparticle-nanofiber network and the back-gate electrode-based control of the Debye screening length. The fabricated BioFET exhibits excellent sensitivity, stability and reproducibility with a rapid response time of 0.8 s. Excellent selectivity towards serotonin in the presence of interfering analytes like ascorbic acid (AA), uric acid (UA), Glucose, Na+, K+, Dopamine (DA) is observed owing to the formation of selective binding complexes between the aromatic amine and β-Bi2O3. The real-time applicability of the sensor was successfully tested using urine samples as a test matrix thus establishing it as a promising platform for label free detection of biomolecules in point-of care diagnostics.