Organic photoelectrochemical transistor aptasensor for dual-mode detection of DEHP with CRISPR-Cas13a assisted signal amplification.

Emerging organic photoelectrochemical transistors (OPECTs) with inherent amplification capabilities, good biocompatibility and even self-powered operation have emerged as a promising detection tool, however, they are still not widely studied for pollutant detection. In this paper, a novel OPECT dual-mode aptasensor was constructed for the ultrasensitive detection of di(2-ethylhexyl) phthalate (DEHP). MXene/In2S3/In2O3 Z-scheme heterojunction was used as a light fuel for ion modulation in sensitive gated OPECT biosensing. A transistor system based on poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) converted biological events associated with photosensitive gate achieving nearly a thousand-fold higher current gain at zero bias voltage. This work quantified the target DEHP by aptamer-specific induction of CRISPR-Cas13a trans-cutting activity with target-dependent rolling circle amplification as the signal amplification unit, and incorporated the signal changes strategy of biocatalytic precipitation and TMB color development. Combining OPECT with the auxiliary validation of colorimetry (CM), high sensitivity and accurate detection of DEHP were achieved with a linear range of 0.1 pM to 200 pM and a minimum detection limit of 0.02 pM. This study not only provides a new method for the detection of DEHP, but also offers a promising prospect for the gating and application of the unique OPECT.

A bioetching-induced visualized-organic photoelectrochemical transistor dual-signal mode sensor for alkaline phosphatase detection.

A study of an integrated OPECT biosensor gate and the EC color-changing region on the same chip was carried out, achieving sensitive detection through bioetching-induced signal changes. Enzymatic bioetching enables specific alkaline phosphatase (ALP) detection by catalyzing the production of CdS, which modulates the channel current and generates a visual signal.

Visualized in-sensor computing.

In artificial nervous systems, conductivity changes indicate synaptic weight updates, but they provide limited information compared to living organisms. We present the pioneering design and production of an electrochromic neuromorphic transistor employing color updates to represent synaptic weight for in-sensor computing. Here, we engineer a specialized mechanism for adaptively regulating ion doping through an ion-exchange membrane, enabling precise control over color-coded synaptic weight, an unprecedented achievement. The electrochromic neuromorphic transistor not only enhances electrochromatic capabilities for hardware coding but also establishes a visualized pattern-recognition network. Integrating the electrochromic neuromorphic transistor with an artificial whisker, we simulate a bionic reflex system inspired by the longicorn beetle, achieving real-time visualization of signal flow within the reflex arc in response to environmental stimuli. This research holds promise in extending the biomimetic coding paradigm and advancing the development of bio-hybrid interfaces, particularly in incorporating color-based expressions.

Ultrasensitive 3D Stacked Silicon Nanosheet Field-Effect Transistor Biosensor with Overcoming Debye Shielding Effect for Detection of DNA.

Silicon nanowire field effect (SiNW-FET) biosensors have been successfully used in the detection of nucleic acids, proteins and other molecules owing to their advantages of ultra-high sensitivity, high specificity, and label-free and immediate response. However, the presence of the Debye shielding effect in semiconductor devices severely reduces their detection sensitivity. In this paper, a three-dimensional stacked silicon nanosheet FET (3D-SiNS-FET) biosensor was studied for the high-sensitivity detection of nucleic acids. Based on the mainstream Gate-All-Around (GAA) fenestration process, a three-dimensional stacked structure with an 8 nm cavity spacing was designed and prepared, allowing modification of probe molecules within the stacked cavities. Furthermore, the advantage of the three-dimensional space can realize the upper and lower complementary detection, which can overcome the Debye shielding effect and realize high-sensitivity Point of Care Testing (POCT) at high ionic strength. The experimental results show that the minimum detection limit for 12-base DNA (4 nM) at 1 × PBS is less than 10 zM, and at a high concentration of 1 µM DNA, the sensitivity of the 3D-SiNS-FET is approximately 10 times higher than that of the planar devices. This indicates that our device provides distinct advantages for detection, showing promise for future biosensor applications in clinical settings.

Enhanced BSA Detection Precision: Leveraging High-Performance Dual-Gate Ion-Sensitive Field-Effect-Transistor Scheme and Surface-Treated Sensing Membranes.

Bovine serum albumin (BSA) is commonly incorporated in vaccines to improve stability. However, owing to potential allergic reactions in humans, the World Health Organization (WHO) mandates strict adherence to a BSA limit (≤50 ng/vaccine). BSA detection with conventional techniques is time-consuming and requires specialized equipment. Efficient alternatives such as the ion-sensitive field-effect transistor (ISFET), despite rapid detection, affordability, and portability, do not detect BSA at low concentrations because of inherent sensitivity limitations. This study proposes a silicon-on-insulator (SOI) substrate-based dual-gate (DG) ISFET platform to overcome these limitations. The capacitive coupling DG structure significantly enhances sensitivity without requiring external circuits, owing to its inherent amplification effect. The extended-gate (EG) structure separates the transducer unit for electrical signal processing from the sensing unit for biological detection, preventing chemical damage to the transducer, accommodating a variety of biological analytes, and affording easy replaceability. Vapor-phase surface treatment with (3-Aminopropyl) triethoxysilane (APTES) and the incorporation of a SnO2 sensing membrane ensure high BSA detection efficiency and sensitivity (144.19 mV/log [BSA]). This DG-FET-based biosensor possesses a simple structure and detects BSA at low concentrations rapidly. Envisioned as an effective on-site diagnostic tool for various analytes including BSA, this platform addresses prior limitations in biosensing and shows promise for practical applications.

Hydrogel-Gated FETs in Neuromorphic Computing to Mimic Biological Signal: A Review.

Hydrogel-gated synaptic transistors offer unique advantages, including biocompatibility, tunable electrical properties, being biodegradable, and having an ability to mimic biological synaptic plasticity. For processing massive data with ultralow power consumption due to high parallelism and human brain-like processing abilities, synaptic transistors have been widely considered for replacing von Neumann architecture-based traditional computers due to the parting of memory and control units. The crucial components mimic the complex biological signal, synaptic, and sensing systems. Hydrogel, as a gate dielectric, is the key factor for ionotropic devices owing to the excellent stability, ultra-high linearity, and extremely low operating voltage of the biodegradable and biocompatible polymers. Moreover, hydrogel exhibits ionotronic functions through a hybrid circuit of mobile ions and mobile electrons that can easily interface between machines and humans. To determine the high-efficiency neuromorphic chips, the development of synaptic devices based on organic field effect transistors (OFETs) with ultra-low power dissipation and very large-scale integration, including bio-friendly devices, is needed. This review highlights the latest advancements in neuromorphic computing by exploring synaptic transistor developments. Here, we focus on hydrogel-based ionic-gated three-terminal (3T) synaptic devices, their essential components, and their working principle, and summarize the essential neurodegenerative applications published recently. In addition, because hydrogel-gated FETs are the crucial members of neuromorphic devices in terms of cutting-edge synaptic progress and performances, the review will also summarize the biodegradable and biocompatible polymers with which such devices can be implemented. It is expected that neuromorphic devices might provide potential solutions for the future generation of interactive sensation, memory, and computation to facilitate the development of multimodal, large-scale, ultralow-power intelligent systems.

High-speed and large-scale intrinsically stretchable integrated circuits.

Intrinsically stretchable electronics with skin-like mechanical properties have been identified as a promising platform for emerging applications ranging from continuous physiological monitoring to real-time analysis of health conditions, to closed-loop delivery of autonomous medical treatment1-7. However, current technologies could only reach electrical performance at amorphous-silicon level (that is, charge-carrier mobility of about 1 cm2 V-1 s-1), low integration scale (for example, 54 transistors per circuit) and limited functionalities8-11. Here we report high-density, intrinsically stretchable transistors and integrated circuits with high driving ability, high operation speed and large-scale integration. They were enabled by a combination of innovations in materials, fabrication process design, device engineering and circuit design. Our intrinsically stretchable transistors exhibit an average field-effect mobility of more than 20 cm2 V-1 s-1 under 100% strain, a device density of 100,000 transistors per cm2, including interconnects and a high drive current of around 2 µA µm-1 at a supply voltage of 5 V. Notably, these achieved parameters are on par with state-of-the-art flexible transistors based on metal-oxide, carbon nanotube and polycrystalline silicon materials on plastic substrates12-14. Furthermore, we realize a large-scale integrated circuit with more than 1,000 transistors and a stage-switching frequency greater than 1 MHz, for the first time, to our knowledge, in intrinsically stretchable electronics. Moreover, we demonstrate a high-throughput braille recognition system that surpasses human skin sensing ability, enabled by an active-matrix tactile sensor array with a record-high density of 2,500 units per cm2, and a light-emitting diode display with a high refreshing speed of 60 Hz and excellent mechanical robustness. The above advancements in device performance have substantially enhanced the abilities of skin-like electronics.

A Drug Molecule-Modified Graphene Field-Effect Transistor Nanosensor for Rapid, Label-Free, and Ultrasensitive Detection of Estrogen Receptor α Protein.

Estrogen receptor α (ERα) is an important biomarker in breast cancer diagnosis and treatment. Sensitive and accurate detection of ERα protein expression is crucial in guiding selection of an appropriate therapeutic strategy to improve the effectiveness and prognosis of breast cancer treatment. Herein, we report a liquid-gated graphene field-effect transistor (FET) biosensor that enables rapid, sensitive, and label-free detection of the ERα protein by employing a novel drug molecule as a capture probe. The drug molecule was synthesized and subsequently immobilized onto the sensing surface of the fabricated graphene FET, which was able to distinguish the ERα-positive from the ERα-negative protein. The developed sensor not only demonstrated a low detection limit (LOD: 2.62 fM) but also achieved a fast response to ERα protein samples within 30 min. Moreover, depending on the relationship between the change of dirac point and the ERα protein concentrations, the dissociation constant (Kd) was estimated to be 7.35 ± 0.06 pM, indicating that the drug probe-modified graphene FET had a good affinity with ERα protein. The nanosensor was able to analyze ERα proteins from 36 cell samples lysates. These results show that the graphene FET sensor was able to differentiate between ERα-positive and ERα-negative cells, indicating a promising biosensor for the ultrasensitive and rapid detection of ERα protein without antibody labeling.

Solution-Induced Degradation of the Silicon Nanobelt Field-Effect Transistor Biosensors.

Field-effect transistor (FET)-based biosensors are powerful analytical tools for detecting trace-specific biomolecules in diverse sample matrices, especially in the realms of pandemics and infectious diseases. The primary concern in applying these biosensors is their stability, a factor directly impacting the accuracy and reliability of sensing over extended durations. The risk of biosensor degradation is substantial, potentially jeopardizing the sensitivity and selectivity and leading to inaccurate readings, including the possibility of false positives or negatives. This paper delves into the documented degradation of silicon nanobelt FET (NBFET) biosensors induced by buffer solutions. The results highlight a positive correlation between immersion time and the threshold voltage of NBFET devices. Secondary ion mass spectrometry analysis demonstrates a gradual increase in sodium and potassium ion concentrations within the silicon as immersion days progress. This outcome is ascribed to the nanobelt's exposure to the buffer solution during the biosensing period, enabling ion penetration from the buffer into the silicon. This study emphasizes the critical need to address buffer-solution-induced degradation to ensure the long-term stability and performance of FET-based biosensors in practical applications.

Hole Mobility Enhancement in Benzo[1,2-b:4,5-b']Dithiophene-Based Conjugated Polymer Transistors through Directional Alignment, Perovskite Functionalization and Solid-State Electrolyte Gating.

Tunability in electronic and optical properties has been intensively explored for developing conjugated polymers and their applications in organic and perovskite-based electronics. Particularly, the charge carrier mobility of conjugated polymer semiconductors has been deemed to be a vital figure-of-merit for achieving high-performance organic field-effect transistors (OFETs). In this study, the systematic hole carrier mobility improvement of benzo[1,2-b:4,5-b']dithiophene-based conjugated polymer in perovskite-functionalized organic transistors is demonstrated. In conventional OFETs with a poly(methyl methacrylate) (PMMA) gate dielectric, improvements in hole mobility of 0.019 cm2 V-1 s-1 are measured using an off-center spin-coating technique, which exceeds those of on-center counterparts (0.22 ± 0.07 × 10-2 cm2 V-1 s-1). Furthermore, the mobility drastically increases by adopting solid-state electrolyte gating, corresponding to 2.99 ± 1.03 cm2 V-1 s-1 for the control, and the best hole mobility is 8.03 cm2 V-1 s-1 (average ≈ 6.94 ± 0.59 cm2 V-1 s-1) for perovskite-functionalized OFETs with a high current on/off ratio of >106. The achieved device performance would be attributed to the enhanced film crystallinity and charge carrier density in the hybrid perovskite-functionalized organic transistor channel, resulting from the high-capacitance electrolyte dielectric.

Power and Sensitivity Management of Carbon Nanotube Transistor Glucose Biosensors.

Continuous glucose monitoring (CGM), which is significant for the daily management of diabetes, requires a low-power-consumption sensor system that can track low nanomolar levels of glucose in physiological fluids, such as sweat and tears. However, traditional electrochemical methods are limited to analytes in micromolar to millimolar ranges and entail high power consumption. Carbon nanotube (CNT) film field-effect transistors (FETs) are promising for constructing extremely sensitive biosensors, but their wide applications in CGM are limited by the strong screening effect of physiological fluids and the zero charge of glucose molecules. In this study, we demonstrate a glucose aptamer-modified CNT FET biosensor to realize a highly sensitive CGM system with sub-nW power consumption by applying a suitable gate voltage. A positive gate voltage can enlarge the effective Debye screening length at the double layer to reduce the local ion population nearby and then improve the sensitivity of the FET-based biosensors by 5 times. We construct CNT FET sensors for CGM with a limit of detection of 0.5 fM, a record dynamic range up to 109, and a power consumption down to ∼100 pW. The proposed field-modulated sensing performance scheme is applicable to other aptamer-based FET biosensors for detecting neutral or less charged molecules and opens opportunities to develop facilely modulated, highly sensitive, low-power, and noninvasive CGM systems.

Silicon nanowire FET biosensor and its application in acute myocardial infarction.

Over the last two decades, silicon nanowire field-effect transistors (SiNW-FETs) with prominent merits of high surface-to-volume ratio, excellent biocompatibility and mature fabrication with standard silicon technology, have been widely studied as ultrahigh sensitive biosensors for the detection of target biomolecules, such as proteins, nucleic acids, cells and viruses so on. Herein we present a comprehensive review of the fundamental aspects of SiNW-FET biosensors, involving the working principle and the device fabrication, surface functionalization, and system integration with fluid exchange and electrical detection. Futhermore, we emphatically discuss the electrical detection of cardiac-specific biomarkers related to acute myocardial infarction disease. SiNW-FET biosensors are being increasingly exploited as promising diagnostic devices, which provide high sensitivity, high integration density, high speed sampling, strong specificity, and real-time and label-free detection for simple and cheap clinical testing.

Adaptive Neural Activation and Neuromorphic Processing via Drain-Injection Threshold-Switching Float Gate Transistor Memory.

Hetero-modulated neural activation is vital for adaptive information processing and learning that occurs in brain. To implement brain-inspired adaptive processing, previously various neurotransistors oriented for synaptic functions are extensively explored, however, the emulation of nonlinear neural activation and hetero-modulated behaviors are not possible due to the lack of threshold switching behavior in a conventional transistor structure. Here, a 2D van der Waals float gate transistor (FGT) that exhibits steep threshold switching behavior, and the emulation of hetero-modulated neuron functions (integrate-and-fire, sigmoid type activation) for adaptive sensory processing, are reported. Unlike conventional FGTs, the threshold switching behavior stems from impact ionization in channel and the coupled charge injection to float gate. When a threshold is met, a sub-30 mV dec-1 increase of transistor conductance by more than four orders is triggered with a typical switch time of approximately milliseconds. Essentially, by feeding light sensing signal as the modulation input, it is demonstrated that two typical tasks that rely on adaptive neural activation, including collision avoidance and adaptive visual perception, can be realized. These results may shed light on the emulation of rich hetero-modulating behaviors in biological neurons and the realization of biomimetic neuromorphic processing at low hardware cost.

pH Quantification in Human Dermal Interstitial Fluid Using Ultra-Thin SOI Silicon Nanowire ISFETs and a High-Sensitivity Constant-Current Approach.

In this paper, we propose a novel approach to utilize silicon nanowires as high-sensitivity pH sensors. Our approach works based on fixing the current bias of silicon nanowires Ion Sensitive Field Effect Transistors (ISFETs) and monitor the resulting drain voltage as the sensing signal. By fine tuning the injected current levels, we can optimize the sensing conditions according to different sensor requirements. This method proves to be highly suitable for real-time and continuous measurements of biomarkers in human biofluids. To validate our approach, we conducted experiments, with real human sera samples to simulate the composition of human interstitial fluid (ISF), using both the conventional top-gate approach and the optimized constant current method. We successfully demonstrated pH sensing within the physiopathological range of 6.5 to 8, achieving an exceptional level of accuracy in this complex matrix. Specifically, we obtained a maximum error as low as 0.92% (equivalent to 0.07 pH unit) using the constant-current method at the optimal current levels (1.71% for top-gate). Moreover, by utilizing different pools of human sera with varying total protein content, we demonstrated that the protein content among patients does not impact the sensors' performance in pH sensing. Furthermore, we tested real-human ISF samples collected from volunteers. The obtained accuracy in this scenario was also outstanding, with an error as low as 0.015 pH unit using the constant-current method and 0.178 pH unit in traditional top-gate configuration.

A Novel Biosensing Approach: Improving SnS2 FET Sensitivity with a Tailored Supporter Molecule and Custom Substrate.

The exclusive features of two-dimensional (2D) semiconductors, such as high surface-to-volume ratios, tunable electronic properties, and biocompatibility, provide promising opportunities for developing highly sensitive biosensors. However, developing practical biosensors that can promptly detect low concentrations of target analytes remains a challenging task. Here, a field-effect-transistor comprising n-type transition metal dichalcogenide tin disulfide (SnS2 ) is developed over the hexagonal boron nitride (h-BN) for the detection of streptavidin protein (Strep.) as a target analyte. A self-designed receptor based on the pyrene-lysine conjugated with biotin (PLCB) is utilized to maintain the sensitivity of the SnS2 /h-BN FET because of the π-π stacking. The detection capabilities of SnS2 /h-BN FET are investigated using both Raman spectroscopy and electrical characterizations. The real-time electrical measurements exhibit that the SnS2 /h-BN FET is capable of detecting streptavidin at a remarkably low concentration of 0.5 pm, within 13.2 s. Additionally, the selectivity of the device is investigated by measuring its response against a Cow-like serum egg white protein (BSA), having a comparative molecular weight to that of the streptavidin. These results indicate a high sensitivity and rapid response of SnS2 /h-BN biosensor against the selective proteins, which can have significant implications in several fields including point-of-care diagnostics, drug discovery, and environmental monitoring.

Covalent functionalisation controlled by molecular design for the aptameric recognition of serotonin in graphene-based field-effect transistors.

In the last decade, solution-gated graphene field effect transistors (GFETs) showed their versatility in the development of a miniaturized multiplexed platform for electrophysiological recordings and sensing. Due to their working mechanism, the surface functionalisation and immobilisation of receptors are pivotal to ensure the proper functioning of devices. Herein, we present a controlled covalent functionalisation strategy based on molecular design and electrochemical triggering, which provide a monolayer-like functionalisation of micro-GFET arrays retaining the electronic properties of graphenes. The functionalisation layer as a receptor was then employed as the linker for serotonin aptamer conjugation. The micro-GFET arrays display sensitivity toward the target analyte in the micromolar range in a physiological buffer (PBS 10 mM). The sensor allows the in-flow real-time monitoring of serotonin transient concentrations with fast and reversible responses.

Carbon dots-functionalized extended gate organic field effect transistor-based biosensors for low abundance proteins.

Organic field effect transistors have emerged as promising platforms for biosensing applications. However, the challenge lies in optimizing functionalization strategies for the sensing interface, enabling the simultaneous detection of low abundance proteins while maintaining device performance. Here, we designed a carbon dots-functionalized extended gate organic field effect transistor. Leveraging the advantages of facile synthesis, tunable modification, small particle size, and cost-effectiveness of carbon dots, we implemented their integration onto the electrode surface. Through harnessing the covalent interactions of functional groups on the surface of carbon dots, we achieved effective immobilization of low abundance proteins without compromising device performance. Consequently, this biosensor exhibits a remarkably low limit of detection of 2.7 pg mL-1 and demonstrates high selectivity for the carcinoembryonic antigen. These findings highlight the superior capabilities of carbon dots in enhancing biosensor performance and emphasize their potential for early cancer detection.

Highly sensitive detection of malaria biomarker through matching channel and gate capacitance of integrated organic electrochemical transistors.

Organic electrochemical transistors (OECTs) possess versatile advantages for biochemical and electrophysiological applications due to electrochemical gating and ion-to-electron conversion capability. Although OECTs have been successfully applied for biochemical sensing, the effect of relative capacitance for specific sensing events is still unclear. In the present work, we design integrated interdigitated OECTs (iOECTs) with on-plane gold gate and different channel geometries for point-of-care diagnosis of malaria using aptamer as receptor. The transconductance of the iOECTs gated with micro-size gold electrodes decreased with increasing the channel thicknesses, especially for devices with large channel areas, which is inconsistent with devices gated by typical Ag/AgCl electrodes, attributing to the limited gating efficiency of the micro-size gate electrode. The capacitance of gate electrode was heavily suppressed by receptors but increased with the incubation of targets. In addition, the integrated iOECTs with thin channels exhibited superior sensitivity for malaria detection with the detection limit as low as 3.2 aM, much lower than their thick channel counterpart and other state-of-the-art biosensors. These deviations could be caused by the high relative capacitances, with respect to the gate and channel capacitance (Cg/Cch), resulting in a high gate potential drop over the organic channel and thus entirely gating on the thin channel device. These findings provide guidance to optimize the geometry of OECT devices with on-chip integrated gates and the fabrication of miniaturized OECTs for biosensing applications.

Biotemplated precise assembly approach toward ultra-scaled high-performance electronics.

Structural DNA nanotechnology can be programmed into complex designer structures with molecular precision for directing a wide range of inorganic and biological materials. However, the use of DNA-templated approaches for the fabrication and performance requirements of ultra-scaled semiconductor electronics is limited by its assembly disorder and destructive interface composition. In this protocol, using carbon nanotubes (CNTs) as model semiconductors, we provide a stepwise process to build ultra-scaled, high-performance field-effect transistors (FETs) from micron-scale three-dimensional DNA templates. We apply the approach to assemble CNT arrays with uniform pitches scaled between 24.1 and 10.4 nm with yields of more than 95%, which exceeds the resolution limits of conventional lithography. To achieve highly clean CNT interfaces, we detail a rinsing-after-fixing step to remove residual DNA template and salt contaminations present around the contact and the channel regions, without modifying the alignment of the CNT arrays. The DNA-templated CNT FETs display both high on-state current (4-15 µA per CNT) and small subthreshold swing (60-100 mV per decade), which are superior to previous examples of biotemplated electronics and match the performance metrics of high-performance, silicon-based electronics. The scalable assembly of defect-free three-dimensional DNA templates requires 1 week and the CNT arrays can be synthesized within half a day. The interface engineering requires 1-2 d, while the fabrication of high-performance FET and logic gate circuits requires 2-4 d. The structural and performance characterizations of molecular-precise DNA self-assembly and high-performance electronics requires 1-2 d. The protocol is suited for users with expertise in DNA nanotechnology and semiconductor electronics.

Highly Effective and Efficient Self-Assembled Multilayer-Based Electrode Passivation for Operationally Stable and Reproducible Electrolyte-Gated Transistor Biosensors.

To ensure the operational stability of transistor-based biosensors in aqueous electrolytes during multiple measurements, effective electrode passivation is crucially important for reliable and reproducible device performances. This paper presents a highly effective and efficient electrode passivation method using a facile solution-processed self-assembled multilayer (SAML) with excellent insulation property to achieve operational stability and reproducibility of electrolyte-gated transistor (EGT) biosensors. The SAML is created by the consecutive self-assembly of three different molecular layers of 1,10-decanedithiol, vinyl-polyhedral oligomeric silsesquioxane, and 1-octadecanethiol. This passivation enables EGT to operate stably in phosphate-buffered saline (PBS) during repeated measurements over multiple cycles without short-circuiting. The SAML-passivated EGT biosensor is fabricated with a solution-processed In2O3 thin film as an amorphous oxide semiconductor working both as a semiconducting channel in the transistor and as a functionalizable biological interface for a bioreceptor. The SAML-passivated EGT including In2O3 thin film is demonstrated for the detection of Tau protein as a biomarker of Alzheimer's disease while employing a Tau-specific DNA aptamer as a bioreceptor and a PBS solution with a low ionic strength to diminish the charge-screening (Debye length) effect. The SAML-passivated EGT biosensor functionalized with the Tau-specific DNA aptamer exhibits ultrasensitive, quantitative, and reliable detection of Tau protein from 1 × 10-15 to 1 × 10-10 M, covering a much larger range than clinical needs, via changes in different transistor parameters. Therefore, the SAML-based passivation method can be effectively and efficiently utilized for operationally stable and reproducible transistor-based biosensors. Furthermore, this presented strategy can be extensively adapted for advanced biomedical devices and bioelectronics in aqueous or physiological environments.