Biologically sensitive field-effect transistors (BioFETs) are one of the most abundant classes of electronic sensors for biomolecular detection. Most of the time these sensors are realized as classical ion-sensitive field-effect transistors (ISFETs) having non-metallized gate dielectrics facing an electrolyte solution. In ISFETs, a semiconductor material is used as the active transducer element covered by a gate dielectric layer which is electronically sensitive to the (bio-)chemical changes that occur on its surface. This review will provide a brief overview of the history of ISFET biosensors with general operation concepts and sensing mechanisms. We also discuss silicon nanowire-based ISFETs (SiNW FETs) as the modern nanoscale version of classical ISFETs, as well as strategies to functionalize them with biologically sensitive layers. We include in our discussion other ISFET types based on nanomaterials such as carbon nanotubes, metal oxides and so on. The latest examples of highly sensitive label-free detection of deoxyribonucleic acid (DNA) molecules using SiNW FETs and single-cell recordings for drug screening and other applications of ISFETs will be highlighted. Finally, we suggest new device platforms and newly developed, miniaturized read-out tools with multichannel potentiometric and impedimetric measurement capabilities for future biomedical applications.
As a prerequisite to the development of real label-free bioassay applications, a high-throughput top–down nanofabrication process is carried out with a combination of nanoimprint lithography, anisotropic wet-etching, and photolithography methods realizing nanoISFET arrays that are then analyzed for identical sensor characteristics. Here, a newly designed array-based sensor chip exhibits 32 high aspect ratio silicon nanowires (SiNWs) laid out in parallel with 8 unit groups that are connected to a very highly doped, Π-shaped common source and individual drain contacts. Intricately designed contact lines exert equal feed-line resistances and capacitances to homogenize the sensor response as well as to minimize parasitic transport effects and to render easy integration of a fluidic layer on top. The scalable nanofabrication process as outlined in this article casts out a total of 2496 nanowires (NWs) on a 4 inch p-type silicon-on-insulator (SOI) wafer, yielding 78 sensor chips based on nanoISFET arrays. The sensor platform exhibiting high-performance transistor characteristics in buffer solutions is thoroughly characterized using state-of-the-art surface and electrical measurement techniques. Deploying a pH sensor in liquid buffers after high-quality gas-phase silanization, nanoISEFT arrays demonstrate typical pH sensor behavior with sensitivity as high as 43 ± 3 mV·pH–1 and a device-to-device variation of 7% at the wafer scale. Demonstration of a high-density sensor platform with uniform characteristics such as nanoISFET arrays of silicon (Si) in a routine and refined nanofabrication process may serve as an ideal solution deployable for real assay-based applications.
Siloxane coatings for surfaces are essential in many scientific and industrial applications. We describe a straightforward gas-phase evaporation technique in inert atmosphere and introduce a practical and reliable silanization protocol adaptable to different silane types. The primary aim of depositing ultrathin siloxane films on surfaces is to enable a reproducible and homogenous surface functionalization without agglomeration effects during the layer formation. To realize high-quality and large-area coatings, it is fundamental to understand the reaction conditions of the silanes, the process of the siloxane layer formation, and the possible influence of the substrate morphology. We used three typical silane types to exemplify the potential and versatility of our process: aminopropyltriethoxysilane, glycidoxypropyltrimethoxysilane, and 1 H,1 H,2 H,2 H-perfluorooctyl-trichlorosilane. The ultrathin siloxane layers, which are generally difficult to characterize, were precisely investigated with high-resolution surface-characterization methods to verify our concept in terms of reproducibility and coating quality. Our results show that this gas-phase evaporation protocol is easily adaptable to all three, widely used silane types also enabling a large-area upscale.
A scalable bottom-up solution-based approach for the site-specific realization of ZnO nanowire (ZnO-NW)-based field-effect transistors for sensing applications in liquids is reported. The nanowires are grown across predefined electrodes patterned by photolithography. Site specificity is attained by the use of nanoparticles acting as seeds. Using integrated on-chip microchannels and microfabricated gate electrodes, electrochemically gated ZnO-NW network transistors functioning in liquids are demonstrated. The optimized devices are rendered sensitive to pH through chemical functionalization. The unique combination of the sensitivity, site specificity, scalability, and cost effectiveness of the technique opens up avenues for the routine realization of one-dimensional nanostructure-based chemical and biosensors for analytical and diagnostic applications.
Silicon nanowire field-effect transistors (SiNW-FET) have been studied as ultra-high sensitive sensors for the detection of biomolecules, metal ions, gas molecules and as an interface for biological systems due to their remarkable electronic properties. “Bottom-up” or “top-down” approaches that are used for the fabrication of SiNW-FET sensors have their respective limitations in terms of technology development. The “bottom-up” approach allows the synthesis of silicon nanowires (SiNW) in the range from a few nm to hundreds of nm in diameter. However, it is technologically challenging to realize reproducible bottom-up devices on a large scale for clinical biosensing applications. The top-down approach involves state-of-the-art lithography and nanofabrication techniques to cast SiNW down to a few 10s of nanometers in diameter out of high-quality Silicon-on-Insulator (SOI) wafers in a controlled environment, enabling the large-scale fabrication of sensors for a myriad of applications. The possibility of their wafer-scale integration in standard semiconductor processes makes SiNW-FETs one of the most promising candidates for the next generation of biosensor platforms for applications in healthcare and medicine. Although advanced fabrication techniques are employed for fabricating SiNW, the sensor-to-sensor variation in the fabrication processes is one of the limiting factors for a large-scale production towards commercial applications. To provide a detailed overview of the technical aspects responsible for this sensor-to-sensor variation, we critically review and discuss the fundamental aspects that could lead to such a sensor-to-sensor variation, focusing on fabrication parameters and processes described in the state-of-the-art literature. Furthermore, we discuss the impact of functionalization aspects, surface modification, and system integration of the SiNW-FET biosensors on post-fabrication-induced sensor-to-sensor variations for biosensing experiments.
The authors present a combined, p-and n-type fabrication process for silicon nanowire field-effect transistor (SiNW FET) biosensors on a 4" wafer format with nanowire widths down to 100 nm and a height of only 42 nm. The full wafer design includes various SiNW FET combinations with metal or electrolyte gate contacts. A top-down fabrication protocol on high-quality silicon-on-insulator wafers is developed. Down-thinning of Si is done by a modified CMOS cleaning solution, which gives the possibility to control the resulting thickness with sub-nm precision. The structuring of SiNW FETs is realized by nanoimprint lithography (NIL) applying a special temperature/ pressure profile. The authors fabricate nano-scale sensor structures and micro-scale contact lines in the same NIL step. Precise control of the imprinting procedure is important for complete filling of the structures. In this project, the authors aim towards complementary device combinations and therefore they characterize the threshold voltage dependency on the device structures. Back-gate contacts at the front-side of the chips enable a control of surface potential shifts. The new SiNW FET sensors can be utilized for biomedical applications, where they are operated in a liquid environment under double-gate configuration using parallel front gating and back gating.
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