Prostate cancer (PCa) ranks as the second prevalent cause of death among men. In the past twenty years, prostate specific antigen has been regarded as the most frequently used and important biomarker for screening, diagnosis, staging and prognosis of PCa [1]. The PSA is produced by the prostate to liquefy the seminal fluids, which is a glycoprotein and circulates in serum by two different molecular morphology: uncomplexed PSA-α1-antichymotrypsin complex (free PSA, fPSA) and complexed PSA (cPSA). The fPSA accouts for 10%-30% of total PSA (tPSA) and other PSA lack immunological activity. For the diagnosis of PCa, the criterion for biomarker of PSA as following: the value of tPSA above 10 ng/ml is evaluated as the positive, indicating high risk of PCa; The value of tPSA below 4 ng/ml is regarded as the negative and low possibility; the value in the range of 4 ng/ml to 10 ng/ml is so-called “grey zone” and the ration of fPSA/tPSA affects the precise diagnosis of PCa.
A variety of techniques have been developed for the determination of fPSA/tPSA including the electrochemical impedimetric immunosensors [2], bead-array fluorescence assay [3] and screen-printed electrochemical biosensor [4]. However above-mentioned immunoassay have suffered from several shortcomings, such as limited sensitivity, sophisticated procedures/operation and hard to miniaturization. Over the past years, organic electrochemical transistors (OECTs) have attracted intensive attentions for various biosensing applications including ions, [5, 6] dopamine [7], cells [8], bacteria [9], pH [10], in virtue of its intrinsic amplification functionality, low operation voltage in aqueous environment [11–14]. The OECTs translate the small signal of ionic fluxes into an amplified electrical readout. As a typical OECTs, a wildly accepted semiconducting poly (3, 4- ethylenedioxythiophene): poly (styrenesulfonate) (PEDOT: PSS) would assist three terminal electrodes (gate, source and drain) to transducer biochemical signal with high gain. In particularly, the gain performance could be evaluated by following equation:
\({G}_{\text{m}}=\frac{\text{W}d}{\text{L}}\mu {C}^{*}({V}_{\text{t}\text{h}}-{V}_{\text{G}})\) (Eq. 1)
where C* is the volumetric capacitance, and Vth is the threshold voltage.
From above relationship, the structure of OECTs and the mobility decide its performance [15–17]. Previous researchers have reported interdigitated structure to improve the ratio of W/L without significantly increasing device area, which validated the feasibility of interdigitated architecture for amplification of OECTs biosensors [18, 19]. Meanwhile, electrodes with multiple spiral have been reported for biosensing applications due to the unique structure [20, 21]. However, the OECTs with interdigitated multiple spiral hasn’t reported for the biosensing of fPSA/tPSA.
Transition metal carbide or nitride (MXene) has been regarded as next-generation two-dimensional (2D) nanomaterials for wide biomedical applications, including biosensing, photocatalysis, supercapacitor and lithium-ion battery, because of its unique characteristics [22–25]. Two-dimensional Ti3C2Tx (MXene) has been recently explored for biosensing, such as glucose [26], hemoglobin [27], gliotoxin [28] and carcinoembryonic antigen (CEA) [29]. Considering the intercalation and delamination of layered carbides and carbonitrides, MXene nanocomposites provide an ideal site for structural rearrangement semiconducting nanomaterials [30–32]. However, there are no reports for combination of MXene and PEDOT: PSS for synergistic determination of fPSA/tPSA.
Herein, in this paper, we proposed a dual OECTs biosensor with optimized electrode architecture and MXene-assisted semiconducting nanomaterials for the ultrasensitive quantification of fPSA/tPSA. Moreover, our assay afforded the enhanced detection limit of fPSA and tPSA protein down to 0.01 pg/ml (S/N > 3), as well as satisfactory selectivity, reproducibility and reliability, comparable to the best previous literatures. Finally, the clinical performance of the dual OECTs biosensor were evaluated against commercial device and demonstrated comparable linear linearity and high correlation coefficient in biosample quantification.