Label-free detection of biomolecules using silicon nanowire ion-sensitive field-effect transistor devices

Abstract

Regular monitoring of the overall health condition of patients is necessary nowadays, as over recent years there are new threats introduced such as changing environmental conditions, depleting food and energy resources, etc. leading to various deadly diseases. In particular it is important to develop point of care (POC) solutions with which it would be possible to detect diseases in early stages, without the need of regular visits to expensive clinics. Due to the advancement in nanotechnology, nanoelectronic sensors (e.g., field-effect transistor (FET) biosensors) are promising towards POC device development. The biomolecule detection with such devices is label-free and they can be used for quantitative, real-time diagnosis. Among FET biosensors, silicon nanowire FET (Si NW FET) devices are at cutting edge, because of their well-known and controllable properties, availability for mass production and good stability. After the first introduction of Si NW FET sensors in 2001, they have been reported for detection of various chemicals and biomolecules with high sensitivity and selectivity.The aim of this thesis work was to develop a high-throughput wafer-scale fabrication for Si NW FETs and to deploy them for reliable chemical and biomolecule sensing applications. To achieve this goal, a fabrication process using a combination of nanoimprint lithography (NIL), photo lithography and wet chemical etching was developed. With this process the Si NW FET pattern consisting of micro- and nano-scale dimensions was processed on wafer-scale using a single NIL step as a relatively inexpensive and fast method. A total of 78 Si NW FET chips measuring 10 mm × 7 mm with 32 identical Si NW FETs in each, were patterned on prime quality 4 silicon on insulator wafers. It was possible to define and control the dimensions of the nanowires precisely, via designing the dimensions of the nanoimprint mould and by controlling the anisotropic wet etching time and etchant solution composition.The fabricated chips were wire bonded on printed circuit board carriers and encapsulated for usage in ion-sensitive field-effect transistor (ISFET) configurations. The Si NW ISFETs were thoroughly characterized by different microscopy and electrical characterization methods in order to study the uniformity and reproducibility of our wafer-scale fabrication process.The devices were also deployed for sensing of chemicals and biomolecules in ISFET configuration. Firstly, proof-of-principle experiments such as pH sensing were carried out. The sensors showed high sensitivity with an average change in threshold voltage of Vth = 43 ± 3 mV/pH. Thereafter, the potentiometric detection of Prostate cancer biomarker (prostate specific antigen (PSA)) in pg/ml range was performed by covalent immobilization of PSA-specific aptamers as specific receptor layer on the Si NW FET surface. Furthermore, the devices were integrated with microfluidics and the PSA-aptamer binding on the Si NW FET surface was confirmed by optical assays. In the end of the thesis work, quantitative, time-dependent detection of other biomarkers such as T cell cytokine (interleukin-4), was executed by connecting the Si NW transistors to a portable measurement system. In an overall view this thesis summarizes an upscale of the fabrication technology for Si NW ISFETs with emphasis on cost-effective, high-throughput fabrication and their usage in various chemical and biomedical applications. Details of the underlying detection mechanisms and future potential as well as limitations of this sensor platform technology are discussed.