In recent years, bioelectronic devices have received a lot of attention due to their extensive applications in various biosensors and bionic components, such as electrochemical [1], surface-enhanced raman spectroscopy (SERS) [2] and enzyme-linked immunosorbent assays (ELISA) [3]. In comparison with conventional methods, organic thin-film transistors (OTFTs)-based biosensors have become a promising analytical technique in the field of life and health analysis because of their simplicity of instrumentation, ease of operation, and efficient analysis of high-throughput signals ^[4][5][4,5].

Generally speaking, the basic parameters for evaluating the performance of OTFTs include mainly: (1) Mobility (μ), single migration velocity of charge carriers in a single-site electric field. (2) On/off ratio (I_on/I_off), the ratio for the current of the device in the on and off states. (3) Threshold voltage (V_th), a minimum gate voltage to turn on the OTFTs. (4) Sub-threshold slope (SS), the swiftness of the OTFTs device when going from the “off” to the “on” state, the basic performance parameters can be obtained by testing the transfer curves or output curves. Generally speaking, OTFTs can be divided into organic field-effect transistors (OFETs) and organic electrochemical transistors (OECTs) due to the different reaction mechanisms and device configurations. The former generally consists of an organic semiconductor layer, a dielectric layer, a gate electrode, a source electrode, and a drain electrode. The latter differs from the former in that an electrolyte medium replaces the dielectric gate layer, which contributed to much lower voltages, typically less than 1 V. Despite the differences in construction, both OFET and OECT devices have shown unique advantages in the field of biochemistry [6]. For instance, the OTFTs can be processed by a low-cost, high-throughput printing/solution coating process with low process temperatures and short production cycles [7]. Moreover, the electrical properties of organic semiconductors (OSCs) can be adjusted by designing the molecular structure or by physical compounding. A wide range of biosensors based on OTFTs technology have been developed and can detect a wide range of biomarkers, such as proteins, DNA, glucose, dopamine, and so on [8]. In addition, the OTFTs-based biosensing platforms can provide reliable and robust detection and monitoring strategies for disease diagnosis and prognosis, which is of great biomedical importance ^[9][10][9,10].

With the improvement in living standards, people are becoming more conscious of life and health. Saliva testing has attracted wide attention because of its advantages, such as convenience sampling, no trauma, and continuous testing. Testing for biomarkers in saliva can monitor and assess a person’s physiological state. A large number of clinical studies can also take samples from saliva to test and analyze them in disease diagnosis [11]. Studies have confirmed that saliva is a complicated matrix containing many biomarkers, such as glucose, hormones, enzymes, nitrogen products, antibodies, etc. As a classical device, OTFTs are receiving increasing attention for measuring biomarkers in complex physiological substrates, including specific analyte substances in saliva ^[12][13][12,13].

Diabetes is a kind of metabolic disease characterized by high blood glucose levels. In recent decades, the incidence of diabetes has increased worldwide and there has been a tendency for diabetes to become more widespread and impact people younger. Studies have shown that blood sugar levels are directly related to glucose concentrations in saliva [14]. The glucose concentration in blood can be obtained by detecting the glucose concentration in saliva to achieve the purpose of non-invasive, quick, and real-time monitoring of blood glucose levels. OTFTs have become one of the most promising tools for diabetes diagnosis, especially as glucose biosensors. Glucose oxidase (Gox) catalyzes the conversion of D-glucose to D-glucose-1,5-lactone with a reduced process. Vigors are reactivated from the reduced state and produce hydrogen peroxide. Because hydrogen peroxide concentration is directly related to the concentration of glucose, hydrogen peroxide is often used to monitor and quantify glucose concentrations. The Malliaras team first reported the application of a poly (3,4-vinyl dioxythiophene):polystyrene sulfonic acid (PEDOT:PSS) based OECT in glucose sensors [15]. In their work, the electrolyte was treated with glucose oxidase. The gate and active layers of OECTs have no surface modifications. Source–drain current in relation to effective gate voltage is generally obtained by varying the MOSFET transfer characteristics at different glucose levels. The response of the devices is correlated with the analyte concentration in the OECT-based enzyme biosensor. They discovered a relationship between the glucose concentration and the source leakage current by calculation. As the glucose concentration increases, there is a correlation shift in the offset voltage. The glucose sensor has a detection limit of about a few μM and provides a good measurement of glucose levels in human saliva. Alternatively, no additional glucose oxidase can be added. Tang et al. [16] developed a new OECT-based glucose sensor. In their work, no additional enzymes need to be added to the solution by manipulating the gate with enzymes and nanoparticles. The Pt electrode surface was modified using multi-walled carbon nanotubes (MWCNTs)-chitosan (CHIT) hybridization and electrodeposition of Pt-NPs prior to Gox immobilization. MWCNT-CHIT/Gox/Pt and CHIT/Gox/Pt-NPs/Pt electrodes were applied as OECT gates for PEDOT:PSS, respectively. It is faster and easier to use in practical applications, and the sensitivity and performance of the device are greatly improved. In this experiment, the gate voltage was chosen to be 0.4 V. At this point, the normalized current response (NCR) was maximum. These two kinds of electrodes for the glucose detection limit of 20 μM and 5 μM, respectively, of glucose concentration in saliva detection, have a high sensitivity. The gate electrode can therefore be selectively modified, making OECT more widely available for other enzyme sensors. To further improve the rapid response to low glucose concentrations, Elkington et al. [17] designed the P3HT/PVP/Nafion:Gox sensor. They used poly (3-hexylthiophene) (P3HT) as the semiconductor layer, and the grid consisted of a thin film of Nafion (a polymer film material) loaded with Gox. The low-voltage OTFTs device can be integrated with Gox without enzyme activity loss and without the chemical modification of the enzyme and polymer matrix, which significantly simplifies the operation process. For this biosensor, the diffusion of glucose is a critical factor in determining the device’s response time. Based on the OTFTs glucose sensor is susceptible to glucose concentration in saliva. It can measure glucose concentrations in saliva ranging from 8 to 200 μM. The feasibility of a low-cost printed saliva glucose biosensor was demonstrated.

OTFTs-based biosensors also hold good promise for monitoring proteins. In total, 25–30% of the proteins in saliva are the same as those contained in blood, and many proteins can be used for clinical disease diagnosis [18]. Macchia et al. [19] reported an electrolyte-gated OFET (EGOFET) fixed-based ~10¹² immunoglobulin-resistant G (IgG) resistance of a single molecule detection platform without a label. The antigen is captured on its millimeter-sized gated plate. Mixed in with saliva approved the selectivity and the capture of the single molecule IgG, without a label, in all 15 IgGs detected in serum. No labels based on the FET of the single-molecule transistor (SiMoT) platform contain a highly filling capture antibody self-assembled monolayer (SAM), covalent attachment on the golden surface gate. The fewer defects in the SAM, the more pronounced the change in the power function caused by a single binding event, the larger the measurable correlation signal, and the steeper the response of the dose profile. To improve the selectivity and reliability of equipment, Macchia et al. further discussed the biosensor based on EGOTFT to measure the trace of the concentration of C-reactive protein (CRP) in human saliva [20]. CRP is an important biomarker of the body’s inflammatory response and is involved in non-specific immunity in the human body. Usually, surgery, accidental trauma, heart attack, rheumatic diseases, and malignant tumors cause an increase in CRP [21]. In their work, P3HT is used as an OSCto form a conductive path between the source and drain contact points, with aqueous as the electrolyte medium. A monolayer functionalized by the self-assembled gate is used to capture the anti-CRP protein. Saliva stock solution was obtained by diluting human saliva with PBS at a ratio of 1:50. The biosensor platform is combined with low-cost manufacturing technologies for the sensitive detection of biomarkers of clinical relevance. Measurement of CRP in the dilution of saliva can be no labels in the saliva of CRP detection selectivity, low LOD to 13 ± 4 protein. This EGOTFT-based biosensor is not only highly sensitive but also has good selectivity. It is not only limited to the detection of markers in saliva but also in tears and urine. For early diagnosis of protein biomarkers detection and no labels of new revolution laid a foundation. The EGOTFT was successfully used as a biosensor by Palazzo et al. [22]. They proved that the EGOFET-based biosensor works in high concentration in the solution (λ = 0.7 nm) and can sensitively detect the distance of the transistor channel protein events of more than 20 nanometers. The bio-EGOFET sensing platform contains a biological layer in the middle of the electrolyte-OSC interface. The bio-layer consists of phospholipid bilayers that are fixed to the surface of the OSC covalently by plasma depositing a functionalized thin layer. This capacitively tuned EGOFETs reaction is almost not sensitive to the Debye length. 

The electrolyte ions in saliva are also an essential indicator of the health of the body. Ion selective field effect transistors (ISFETs) are OTFTs that can detect saliva pH and ions [23]. Many electrolyte ions, such as calcium, potassium, and sodium ions, are present in human body fluids (including saliva). Electrolytes in the body maintain the body’s pH balance, osmotic pressure balance, and cells’ structural and functional integrity. They are also involved in nerve conduction and metabolism in the body. Bao et al. [24] put forward printing the organic and inorganic ion selective electrode transistor hybrid to prepare flexible ISFET. They were used to detect potassium (K⁺), calcium (Ca²⁺) and ammonium (NH₄⁺) ions in saliva. The presented serpentine trench design proves that the transistor has good uniform trench reproducibility. The prepared ISFET is highly reliable with the slope of the potential versus ion concentration curve with negligible value variation. During the operation of the device, the change of ion concentration in the movement of the ion-selective membrane potential, as well as the changes between the source and drain current. The ISFET can detect K⁺, NH₄⁺, and Ca²⁺ at 10⁻⁶~1 M, 10⁻⁶~1 M, and 10⁻⁴~1 M, which exhibits good selectivity and immunity without interference by other ions. In addition to the biomarkers mentioned above, tests for peptides, such as oxytocin, have also been investigated. Oxytocin simple detection can contribute to the basic research of diagnosis, maternal care, pharmacology, and molecular biology.

Sweat has gained much attention as a potential source of body fluids due to its close connection to health and disease. It is readily obtained from the skin surface in humans, including separated from the blood of the specific biomarkers ^[25][26][27,28]. The main component of human sweat is water (99%). However, it also contains various trace components, such as protein, fatty acids, electrolytes, metabolites, etc., which can indicate fatigue, body diseases, dehydration, and emotional stress ^[27][29]. Thus, sweat may be a possibility to be a biomarker of a non-invasive nature. With the biosensor field’s rapid development, sweat biomarkers analysis has become a trend, oriented toward monitoring disease and managing health. This is because the biomarker of human sweat is at a significantly lower concentration than the biomarker of blood ^[28][30], the sensor requires high sensitivity and selectivity.

Glucose in sweat is one of the most attractive markers for researchers. Sweat and the correlation between blood glucose levels are used to diagnose diabetes. The OECT obtained by screen printing by Scheiblin et al. ^[29][31] detects glucose and lactic acid. The transistor uses a solid electrolyte containing reagent and is capable of detecting glucose and lactate in a small amount of media. They selected an organically modified sol-gel electrolyte in which the enzyme is encapsulated. The stability of the equipment and the capability to perform a long period of storage, and the influence of other interfering substances in the medium, are issues that need to be resolved in the future. However, the sensor has a high detection limit. The thinner PB membrane has a solid and stable electrocatalytic activity at low operating potentials with high susceptibility and a high degree of selectivity, thus facilitating the assay of glucose in sweat at low H₂O₂ concentrations ^[30][32]. To further improve sensitivity and stability in liquid phase detection, Mano et al. ^[31][33] developed an enzyme sensor based on OFET. Its low cost, high sensitivity, and biocompatibility were used to detect glucose accurately. D-glucose and Gox undergo an enzymatic reaction to produce hydrogen peroxide, and the extended grid electrode continuously monitors glucose levels. The reducing medium PB is then oxidized by hydrogen peroxide from divalent to trivalent. The potentiometric redox difference between the electrodes induces the redox cycle of PB. Therefore, expanding the grid potential changes is based on the Nernst equation. This leads to a change in the threshold voltage (V_th) or source-drain current (I_ds) of the OFET. The sensor of D-glucose displayed a gradually stable and reversible reaction. Glucose concentrations of 0.01~1.11 mM in sweat can be detected without adding other chemical reagents. The response to glucose levels in tears and saliva is equally good. OTFTs-based biosensors have come a long way, and rapid detection of target analytes with low-cost devices in complex environments is no longer a fantasy. In the future, OTFTs sensors in wearable smart devices, real-time health monitoring, and artificial electronic skin and organs will have critical applications.

In addition to detecting glucose in sweat, OTFT can also detect cortisol levels. The optimal concentration of cortisol in sweat is between 0.02 and 0.5 μM ^[32][34]. Cortisol is an adrenal corticosteroid hormone, often referred to as the “stress hormone” ^[33][35]. Elevated levels of cortisol can have a negative impact on a person’s health. Persistent stress can impair the balance of the heart, kidneys, bones, and internal secretion system, resulting in the progressive progression of chronic diseases. It increases the likelihood of depression, suicide, and anxiety ^[34][36]. The approach is to embed cortisol antibodies in polystyrene-methacrylic acid (PSMA) to form membranes that are selective and sensitive to cortisol. Receptors in the polymer-anchored structure enable cortisol atoms in the film matrix near the interface combination. They designed a sensor with high sensitivity and low detection limits (down to 1 pg/mL). The OECT sensor enables cortisol detection by functionalizing the molecularly imprinted membrane (MIM) only. The technology of increased use in clinical environment transistor biological sensors detect the possibility of cortisol in saliva or sweat. Parlak et al. ^[35][37] subsequently developed an artificially recognizable molecularly printed polymers-based membrane that was inserted between the PEDOT:PSS channel layer and the analyte (sweat) to manage and regulate the direct segregative molecular transport of cortisol from the surface of the skin to the OECT sensor sensing channel. Cortisol concentration in 0.01~10.0 μM is a logarithmic, linear response range. Electrochemical crystals and integration of bionic polymer membrane, with high sensitivity, promote stability and selectivity of cortisol molecular recognition. The design principle of selective detection can also be applied to other molecules, such as electrically neutral biological molecules. They have demonstrated the integration of a biomimetic polymer membrane that performs stable, rapid, and specific molecular recognition through the OECTs for real-time response to changes in cortisol concentration. This wearable sensor, by conducting polymers channel and the flexible can choose membrane tensile elastic substrate to produce cortisol functionalization. This biosensor can collect discharge sweat when people move, similar to the motion of normal human skin under the condition of tensile and bending. In addition, they designed a system of passive fluid manipulation. The system is composed of the design of a laser micro-capillary channel array. Sweat can be quickly and accurately to directly to the sensor interface. Wearable sweat diagnosis platforms of miniaturization and non-invasive sweat induction are the future development direction.

To reduce the detection limits of the sensor, Janardhanan et al. ^[36][38] designed a novel OECT cortisol immune sensor. The sensor in the activity of the OECT device channel area using poly (EDOT-COOH-co-EDOT-EG3) nanotubes and PEDOT:PSS base enhances the sweat of cortisol in response to the human body. The OECT cortisol immunosensor can detect cortisol linearly in the concentration range of 1 fg/mL to 1 μg/mL, the limit of detection (LOD) is 0.0088 fg/mL, and the linearity is excellent (R² = 0.9566). Due to the sensor showing good stability and repeatability, the author thinks it has clinical application in future healthcare monitoring application potential. OTFTs also respond well to changes in the pH of sweat. Chronically high-stress levels can affect a person’s physical health and psychological condition, such as high blood pressure and depression. pH can provide appropriate information about emotional and bodily stress ^[37][40]. Ching-Mei et al. ^[38][41] proposed a new method of stress state monitoring using disposable flexible sensors. The electrode based on OTFT was fabricated by full vacuum printing technology. Polymer thin films were deposited rapidly by flash evaporation and combined with semiconductor dinaphtho[2,3-b:2′,3′-f]thieno[3,2-b] thiophene (DNTT) to form devices with high reproductivity and high yield. A signal amplification front-end circuit based on an OTFT was used to capture biological signals using the piezoelectric response of polyvinylidene difluoride (PVDF) combined with the pH evaluation of sweat. The sensor’s response time is stable, repeatable, and fast (less than 20 s), with a sensitivity of 62.8 mV per unit pH. Similarly, Mariani et al. [39] showed an OECT sensor for pH monitoring. To pH signature transmission, PEDOT:dye composites by photochemical pH dye-doped (MO and BTB, methyl orange and bromothymol blue) composite. They have evaluated the two kinds of materials to the pH change of electrochemical reaction. The sensitivity of PEDOT:BTB was 62 ± 2 mV per pH unit, and that of PEDOT:MO was 31 ± 2 mV per pH unit. Based on pH monitoring, OTFT sensors applied in health care and portable sensing technology will have a good prospect in the future.

The testing of dopamine has likewise attracted a substantial amount of attention. Dopamine is an essential neurotransmitter that is widely present in the central nervous system, helping nerve cells to transmit a variety of physiological signals and maintain normal body functions. When its concentration is abnormal, it may lead to various diseases, such as Tourette’s disease, Schizophrenia, Parkinson’s disease, and Pituitary tumors ^[40][42]. Tang H et al. ^[41][43] suggested using PEDOT:PSS. By comparing different types of grids, including graphite (GE), gold, and platinum electrodes, and GE modified using a mixture of multi-walled carbon nanotube (MWCNT)-chitosan (CHIT) and Pt electrodes, they found that the apparatus with Pt grids exhibited the best limit of detection (less than 5 nM). However, the sensor was not selective for dopamine. Gualandi et al. ^[42][44] prepared a sensor based on PEDOT:PSS OECTs to selectively detect dopamine with a 6 μM detection limit. Xing Q et al. ^[43][45] designed and fabricated a novel polypyrrole/nanofibers/polyamide 6 (PPy/NFs/PA6) filamentous electrochemical transistor. The magnification ratio and current response rate were significantly better than those of conventional OECTs, with excellent sensitivity even at dopamine concentrations as low as 1 nM. Finally, Shiwaku et al. ^[44][46] demonstrated a novel potentiometric electrochemical sensing system in terms of electrolyte ions. Lack of potassium ions in the human body results in symptoms such as muscle weakness, body fatigue, loss of appetite, and tachycardia. They used two negative feedback inverters based on OTFTs. The inverters used a low molecule p-type semiconductor, 2,7-dihexyl-dithieno[2,3-d; 2′,3′-d′]benzo[1,2-b; 4,5-b′]dithiophene (DTBDT-C₆), and polystyrene (PS) as the reactive layer. The ion concentration sensitivity sensor for K⁺ of 34 mV/dec was prepared and scaled up to 160 mV/dec with high linearity, enabling the measurement of K⁺ levels by in situ human sweat analysis. The results show that potential galvanic sensors based on organic circuit printed devices are achievable.

There are a variety of biomarkers in urine, so people think of effective real-time detection of human health by monitoring abnormal components in urine. The are now several urine sample detection methods, such as gas chromatography/mass spectrometry (GC/MS) ^[45][47], liquid chromatography/mass spectrometry (LC/MS), and so on ^[46][48]. However, such as the need for professional operation, long response time and high production cost, the requirements for professional venues are all problems that have yet to be solved in this industry. Sensors based on OTFT have the following advantages: high sensitivity, simple manufacturing, short reaction time, and so on, which have a good application prospect in the current industry ^[47][48][49,50]. In recent years, many applications for the OTFT principle of biosensors in actual diagnoses have been found, such as pulse oximetry ^[49][51], temperature/pressure signals, and electrophysiology arrays ^[50][52]. Although these biosensors are widely used, the stability and sensitivity of practical applications are challenging in this field. Hereupon, to mitigate this challenge, Hu et al. ^[51][53] studied the preparation of an OECT sensor using PEDOT:PSS as channel material and gold nanoparticles were mixed on the carbon tube to modify OECT, which improved the sensitivity of the sensor very efficiently and could effectively measure the content of dopamine in urine in a short time. It is a sensor with broad prospects ^[52][54].

To further optimize portability and sensitivity, Y. Pan et al. ^[53][60] designed a graphene polymer-functionalized FETportable biomarker sensor, mainly used in real-time glucose monitoring. The biosensor polymer is synthesized from acrylamide/3-acrylamide phenylboronic acid (AAPBA)/N,N-dimethylamino-acrylamide. The biosensor mechanism is that when glucose is present, polymers appear on graphene, and the covalent bonds produced by the reaction of glucose and AAPBA lead to Dirac point shift and current change in the polymer functionalized graphene field-effect transistor (P-GFET) ^[54][61].

There have also been significant advances in the detection of transitioned urine. The kidneys play a crucial role in the circulation system. Gundlach et al. ^[55][62] developed a new device design method. They measured the magnetoconductance (MC) by manipulating the spin process. The authors manipulated the carrier migration by regulating the gate voltage, and they successfully observed the fission process of MC. Hamzah et al. ^[56][63] have developed and designed an extremely accurate transistor sensor modified with antidiuretic hormone (ADH) antibodies on graphene. They also demonstrated in later experiments that the sensor could detect not only human urine but also proteins in the blood. Subsequently, OTFT-based biosensors could also play an essential role in detecting other diseases. For many years, the complex urine environment and low levels of cancer-related markers have been challenging in this field. Yang et al. ^[57][64] developed a sensor for detecting malignant bladder tumors, which can detect single-stranded nucleic acid in urine and has good repeatability and functional stability. In addition, there has been some progress in detecting trace elements in the human body. In the middle of 2022, Patolsky et al. ^[58][65] developed an ultra-sensitive biosensor which modified the uranyl junction fit body into a nano silicon transistor. This biosensor is easy to operate and can directly detect the content of uranyl ions in human urine.

In terms of early detection of cancer, the urine diagnostic method for bladder cancer was developed by Quan et al. ^[59][66]. In 2020, low accuracy appeared in terms of detection sensitivity. A high-precision molybdenum disulfide (MoS₂) nanosheet FET sensor array was developed for real-time monitoring of bladder cancer biomarkers in human urine. Quan et al. ^[60][67] designed an indium gallium zinc oxide field effect transistor (IGZO FET) biosensor array last year, which can be connected to Internet terminals to make a human urine analysis assay device for detecting biomarkers of bladder cancer in urine, and realized clinical detection. The FEThas a good application prospect in urine detection [6]. Their IGZO FET-based biosensor, which can be connected to an Internet terminal, provides high sensitivity and selectivity in the actual complex urine test. These works highlight the wide range of applications of OTFT-based biosensors for the non-invasive, ultra-sensitive biological detection of urine. These designs, which can be summarized as the features of man-carried, penny-a-line, non-invasie, automated data processing and analysis, and no need for the professional operation of professionals, are expected to be translated into standard clinical practice in the diagnosis and prognosis of serious diseases.

There are some charged biomarkers in blood which can be used for real-time monitoring of human physiological conditions, and also have essential application prospects in the early detection of various diseases ^[61][68]. Most current blood tests are usually combined with blood pressure measurement, albuminuria, and biochemical and hematological assessment. However, in modern centralized laboratories, this usually takes 4–6 h, and comprehensive albuminuria assessment can take up to 24 h ^[62][63][69,70]. Most importantly, clinical manifestations vary so much that it is difficult to objectively determine which patients need urgent medical attention and which patients can continue to use before testing some data for subsequent diagnosis ^[64][65][71,72]. However, most existing traditional detection methods require that the experimental analysis be carried out by professional technical personnel and professional analysis sites, which leads to the diagnosis in some special cases and limits the application in the actual situation. In the past, the Triage-Alere placental growth factor (PLGF) test has been considered a very timely and effective medical treatment ^[66][67][73,74]. However, the actual situation is that this method requires ethylene diamine tetraacetic acid (EDTA) clotting vein puncture blood, and the following steps require professionally trained personnel for blood drawing and condensation, as well as the problematic operation of daily calibration and routine quality control inspection of the fluorescent reader ^[68][75]. This has led to the use of the device in remote areas, and the disease is characterized by higher demand for the technology in remote areas ^[69][76].

The blood test is an important parameter of biological detection therapy. Because of this, OTFT-based biomarker sensors for blood testing were well developed over the next few decades. For example, Abdollahi et al. ^[70][77] summarized some aspects of early diagnosis of diabetes and the management of different biomarkers, including fluorescence, nanotechnology, electrochemical detection, and FET biosensors, and they made early diagnosis of diabetes a research focus. This research project lays a foundation for further development in the later period. Torsi et al. [19] have made some progress in detecting transistor-based biomarkers. In the past, traditional methods that used nano sensors were not effective in complex environments. To alleviate this challenge, they modified the surface of the sensor; capturing the anti-immunoglobulin and modifying a hydrogen bond network onto the surface of the sensor resulted in a good recognition effect in serum detection. Elnathan et al. ^[71][78] further discussed the field effect performance of single-molecule and multi-molecule components on the basis of the former, and they believed that the practicability of the device was the top priority. They believed that the implementation of grid voltage regulation could effectively promote the gating of single-molecule components. Although they only put forward a theory, they provide more possibilities for subsequent development. According to the literature summary above, Zhang et al. ^[72][79] developed a sensor based on the FET principle modified with gold nanoparticles and two ligands for the detection of specific cell derivatives. They made a portable platform for the detection of serum proteins related to liver cancer, as well as for the differentiation of other cancers.

Huang et al. ^[73][74][80,81] designed a new method of mercury ion (Hg²⁺) FET sensor using (ZnO-NB) nanoribbon as thin film channel material. The Langmuir-Blodgett (L-B) assembly technique was used to prepare different types of FET chips by taking advantage of the different concentrations of ZnO-NB. Afterward, Chen et al. ^[75][82] designed a new type of glycosylated hemoglobin-specific nucleic acid ligand (Apt_GP). The sensor-measured ligand phylogenetic assays by exponential enrichment (SELEX) showed strong associations with GP or HbA1c but negligible binding to glycosylated hemoglobin A1c (HbA1c) and non-glycosylated polypeptide. In addition, molecular modeling of GP-Apt_GP compounds and previous studies have shown that hydrogen bonding dominates the binding of GP-Apt_GP, and non-covalent bonds of GP ligands are first bound to the front end of Apt_GP, thus affecting the amino acid arrangement of the peptide chain. The sensor described above is less invasive and more timely than previously reported sensors, but it lacks some accuracy. So, to solve the problem of accuracy and sensitivity, Lee et al. ^[76][83] developed electrolyte-gating graphene FET sensors. This device can effectively detect tau protein through an optimized, connectionless antibody fixation process. In their paper, they show that two-dimensional graphene is classified into eight different types, modified FET sensors are connected to them, and their performance is tested. Experiments have shown that the sensor they designed has antibodies modified on the edges and dope-like behavior on the graphene. When the tau protein in the electrolyte increases to a particular concentration, compared with the original graphene sensor connected by PSE, the graphene sensor they designed and developed, which does not use a linker, shows greater sensitivity.

In 2021, with further improvements having been made on the basis of the previous ones, Thierry et al. ^[77][84] designed and developed a nanoscale indium oxide FET sensor that is completely based on a biological diagnostic platform. Later, they developed a portable sample processing device that integrates blood, thus greatly reducing the need for professional operation. In addition, the device can measure PLGF in about 30 µL of blood samples in just 40 min, with a dynamic range of five orders of magnitude. In 2022, Kordrostami et al. ^[78][85] further improved the sensitivity. Their research and development were on the principle of FET detecting glucose sensors with high sensitivity and accuracy. Their paper shows that the flexible FET biosensor can directly detect glucose in the blood and make a portable dipstick device. The reduced graphene oxide (rGO)-modified CuO nanostructured hollow micro-spheres (NHS) synthesized in this way are deposited on a flexible polyethylene terephthalate (PET) substrate as a channel for the back gate transistor. Furthermore, they have improved both the concentration and the sensor to bring a higher level of accuracy and precision. As reported in the above two articles, both OFET and OECT prototype sensors have greatly improved the sensitivity and accuracy of biometric identification samples, and both have good stability, but there is still a lack of portability. On this basis, Wang et al. ^[79][86] made further improvements in the simplicity and sensitivity of use.

Later, to alleviate this challenge, Rajeswari et al. developed graphene field effect transistors that can detect a variety of myoglobin biomarkers at low concentrations ^[80][88], and graphene itself is an excellent material to use as a grid because of its sensitivity to a variety of other biomarkers. When the graphene FET they designed was built to detect myoglobin antigen, there was a significant change in the current. With a 30 fg/mL strategy level, they have also made a lab-on-a-chip portable device that provides a strong foundation for cardiac care and more. In addition, Sun et al. ^[81][89] further optimized the sensitivity of the sensor on this basis. They developed a new organic material, 2,6-bis(4-formyl phenyl)-anthracene (BFPA), and used it as the channel of OFET biosensor. It achieves the ultra-sensitive detection of alpha-fetoprotein (AFP) in human blood samples and shows that the changes in source leakage current and threshold voltage electrical signals fluctuate significantly with the change of concentration. This device can distinguish liver cancer patients and healthy people very efficiently. It lays a foundation for follow-up research on blood detection.