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Potentiometric sensors based on silicon nanowire field effect transistors (SiNW FETs) typically display exquisite sensitivities, but their bioanalytical implementation is limited due to the need for stringent measurement conditions and high-precision readout units. An alternative operation principle where SiNW FETs are operated in a frequency-domain electrical impedimetric approach is promising. However, to date only limited data is available in regard to the sensing performance and translational relevance of this novel approach in comparison to the standard charge detection paradigm. We demonstrate the feasibility of conducting electrical impedimetric FET measurements with a portable unit for the ultrasensitive detection of cancer biomarkers in biospecimens. Compared to standard potentiometric measurements, electrical impedimetric FET measurements yielded significant improvements in biosensing performances, including the limit of detection, sensing resolution, and dynamic range.

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Within an hour, as little as one disseminated tumor cell (DTC) per lymph node can be quantitatively detected using an intraoperative biosensing platform based on silicon nanowire field-effect transistors (SiNW FET). It is also demonstrated that the integrated biosensing platform is able to detect the presence of circulating tumor cells (CTCs) in the blood of colorectal cancer patients. The presence of DTCs in lymph nodes and CTCs in peripheral blood is highly significant as it is strongly associated with poor patient prognosis. The SiNW FET sensing platform out-performed in both sensitivity and rapidity not only the current standard method based on pathological examination of tissue sections but also the emerging clinical gold standard based on molecular assays. The possibility to achieve accurate and highly sensitive analysis of the presence of DTCs in the lymphatics within the surgery time frame has the potential to spare cancer patients from an unnecessary secondary surgery, leading to reduced patient morbidity, improving their psychological wellbeing and reducing time spent in hospital. This study demonstrates the potential of nanoscale field-effect technology in clinical cancer diagnostics.

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An integrated translational biosensing technology based on arrays of silicon nanowire field-effect transistors (SiNW FETs) is described and has been preclinically validated for the ultrasensitive detection of the cancer biomarker ALCAM in serum. High-quality SiNW arrays have been rationally designed toward their implementation as molecular biosensors. The FET sensing platform has been fabricated using a complementary metal oxide semiconductor (CMOS)-compatible process. Reliable and reproducible electrical performance has been demonstrated via electrical characterization using a custom-designed portable readout device. Using this platform, the cancer prognostic marker ALCAM could be detected in serum with a detection limit of 15.5 pg/mL. Importantly, the detection could be completed in less than 30 min and span a wide dynamic detection range (∼10(5)). The SiNW-on-a-chip biosensing technology paves the way to the translational clinical application of FET in the detection of cancer protein markers.

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Nanoscale redox cycling is a powerful technique for detecting electrochemically active molecules, based on fast repetitive oxidation and reduction reactions. An ideal implementation of redox cycling sensors can be realized by nanoporous dual-electrode systems in easily accessible and scalable geometries. Here, we introduce a multi-electrode array device with highly efficient nanoporous redox cycling sensors. Each of the sensors holds up to 209,000 well defined nanopores with minimal pore radii of less than 40 nm and an electrode separation of ~100 nm. We demonstrate the efficiency of the nanopore array by screening a large concentration range over three orders of magnitude with area-specific sensitivities of up to 81.0 mA (cm(-2) mM(-1)) for the redox-active probe ferrocene dimethanol. Furthermore, due to the specific geometry of the material, reaction kinetics has a unique potential-dependent impact on the signal characteristics. As a result, redox cycling experiments in the nanoporous structure allow studies on heterogeneous electron transfer reactions revealing a surprisingly asymmetric transfer coefficient.

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Ion-sensitive field effect transistors with gates having a high density of nanopores were fabricated and employed to sense the neurotransmitter dopamine with high selectivity and detectability at micromolar range. The nanoporous structure of the gates was produced by applying a relatively simple anodizing process, which yielded a porous alumina layer with pores exhibiting a mean diameter ranging from 20 to 35 nm. Gate-source voltages of the transistors demonstrated a pH-dependence that was linear over a wide range and could be understood as changes in surface charges during protonation and deprotonation. The large surface area provided by the pores allowed the physical immobilization of tyrosinase, which is an enzyme that oxidizes dopamine, on the gates of the transistors, and thus, changes the acid-base behavior on their surfaces. Concentration-dependent dopamine interacting with immobilized tyrosinase showed a linear dependence into a physiological range of interest for dopamine concentration in the changes of gate-source voltages. In comparison with previous approaches, a response time relatively fast for detecting dopamine was obtained. Additionally, selectivity assays for other neurotransmitters that are abundantly found in the brain were examined. These results demonstrate that the nanoporous structure of ion-sensitive field effect transistors can easily be used to immobilize specific enzyme that can readily and selectively detect small neurotransmitter molecule based on its acid-base interaction with the receptor. Therefore, it could serve as a technology platform for molecular studies of neurotransmitter-enzyme binding and drugs screening.

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