In-situ doped junctionless polysilicon nanowires field effect transistors for low-cost biosensors

AbstractSilicon nanowire (SiNW) field effect transistor based biosensors have already been proven to be a promising tool to detect biomolecules. However, the most commonly used fabrication techniques involve expensive Silicon-On-Insulator (SOI) wafers, E-beam lithography and ion-implantation steps. In the work presented here, a top down approach to fabricate SiNW junctionless field effect biosensors using novel in-situ doped polysilicon is demonstrated. The p-type polysilicon is grown with an optimum boron concentration that gives a good metal-silicon electrical contact while maintaining the doping level at a low enough level to provide a good sensitivity for the biosensor. The silicon nanowires are patterned using standard photolithography and a wet etch method. The metal contacts are made from magnetron sputtered TiW and e-beam evaporation of gold. The passivation of electrodes has been done by sputtered Si3N4 which is patterned by a lift-off process. The characterization of the critical fabrication steps is done by Secondary Ion Mass Spectroscopy (SIMS) and by statistical analysis of the measurements made on the width of the SiNWs. The electrical characterization of the SiNW in air is done by sweeping the back gate voltage while keeping the source drain potential to a constant value and surface characterization is done by applying liquid gate in phosphate buffered saline (PBS) solution. The fabricated SiNWs sensors functionalized with (3-aminopropyl)triethoxysilane (APTES) have demonstrated good sensitivity in detecting different pH buffer solutions

A device for extraction, manipulation and stretching of DNA from single human chromosomes

We describe the structure and operation of a micro/nanofluidic device in which individual metaphase chromosomes can be isolated and processed without being displaced during exchange of reagents. The change in chromosome morphology as a result of introducing protease into the device was observed by time-lapse imaging; pressure-driven flow was then used to shunt the chromosomal DNA package into a nanoslit. A long linear DNA strand (>1.3 Mbp) was seen to stretch out from the DNA package and along the length of the nanoslit. Delivery of DNA in its native metaphase chromosome package as well as the microfluidic environment prevented DNA from shearing and will be important for preparing ultra-long lengths of DNA for nanofluidic analysis

A compact multifunctional microfluidic platform for exploring cellular dynamics in real-time using electrochemical detection

Downscaling of microfluidic cell culture and detection devices for electrochemical monitoring has mostly focused on miniaturization of the microfluidic chips which are often designed for specific applications and therefore lack functional flexibility. We present a compact microfluidic cell culture and electrochemical analysis platform with in-built fluid handling and detection, enabling complete cell based assays comprising on-line electrode cleaning, sterilization, surface functionalization, cell seeding, cultivation and electrochemical real-time monitoring of cellular dynamics. To demonstrate the versatility and multifunctionality of the platform, we explored amperometric monitoring of intracellular redox activity in yeast (Saccharomyces cerevisiae) and detection of exocytotically released dopamine from rat pheochromocytoma cells (PC12). Electrochemical impedance spectroscopy was used in both applications for monitoring cell sedimentation and adhesion as well as proliferation in the case of PC12 cells. The influence of flow rate on the signal amplitude in the detection of redox metabolism as well as the effect of mechanical stimulation on dopamine release were demonstrated using the programmable fluid handling capability. The here presented platform is aimed at applications utilizing cell based assays, ranging from e.g. monitoring of drug effects in pharmacological studies, characterization of neural stem cell differentiation, and screening of genetically modified microorganisms to environmental monitoring

Conducting polymer 3D microelectrodes

Conducting polymer 3D microelectrodes have been fabricated for possible future neurological applications. A combination of micro-fabrication techniques and chemical polymerization methods has been used to create pillar electrodes in polyaniline and polypyrrole. The thin polymer films obtained showed uniformity and good adhesion to both horizontal and vertical surfaces. Electrodes in combination with metal/conducting polymer materials have been characterized by cyclic voltammetry and the presence of the conducting polymer film has shown to increase the electrochemical activity when compared with electrodes coated with only metal. An electrochemical characterization of gold/polypyrrole electrodes showed exceptional electrochemical behavior and activity. PC12 cells were finally cultured on the investigated materials as a preliminary biocompatibility assessment. These results show that the described electrodes are possibly suitable for future in-vitro neurological measurements

Fabrication and Characterization of 3D Micro- and Nanoelectrodes for Neuron Recordings

In this paper we discuss the fabrication and characterization of three dimensional (3D) micro- and nanoelectrodes with the goal of using them for extra- and intracellular studies. Two different types of electrodes will be described: high aspect ratio microelectrodes for studying the communication between cells and ultimately for brain slice recordings and small nanoelectrodes for highly localized measurements and ultimately for intracellular studies. Electrical and electrochemical characterization of these electrodes as well as the results of PC12 cell differentiation on chip will be presented and discussed

Real-time monitoring of cellular dynamics using a microfluidic cell culture system with integrated electrode array and potentiostat

A versatile microfluidic, multichamber cell culture and analysis system with an integrated electrode array and potentiostat suitable for electrochemical detection and microscopic imaging is presented in this paper. The system, which allows on-line electrode cleaning and modification, was developed for real-time monitoring of cellular dynamics, exemplified in this work by monitoring of redox metabolism inside living yeast cells and dopamine release from PC12 cell

Metaphase FISH on a Chip: Miniaturized Microfluidic Device for Fluorescence in situ Hybridization

Fluorescence in situ Hybridization (FISH) is a major cytogenetic technique for clinical genetic diagnosis of both inherited and acquired chromosomal abnormalities. Although FISH techniques have evolved and are often used together with other cytogenetic methods like CGH, PRINS and PNA-FISH, the process continues to be a manual, labour intensive, expensive and time consuming technique, often taking over 3 5 days, even in dedicated labs. We have developed a novel microFISH device to perform metaphase FISH on a chip which overcomes many shortcomings of the current laboratory protocols. This work also introduces a novel splashing device for preparing metaphase spreads on a microscope glass slide, followed by a rapid adhesive tape-based bonding protocol leading to rapid fabrication of the microFISH device. The microFISH device allows for an optimized metaphase FISH protocol on a chip with over a 20-fold reduction in the reagent volume. This is the first demonstration of metaphase FISH on a microfluidic device and offers a possibility of automation and significant cost reduction of many routine diagnostic tests of genetic anomalies

Paper-based sensors for rapid detection of virulence factor produced by Pseudomonas aeruginosa

Pyocyanin is a toxin produced by Pseudomonas aeruginosa. Here we describe a novel paper-based electrochemical sensor for pyocyanin detection, manufactured with a simple and inexpensive approach based on electrode printing on paper. The resulting sensors constitute an effective electrochemical method to quantify pyocyanin in bacterial cultures without the conventional time consuming pretreatment of the samples. The electrochemical properties of the paper-based sensors were evaluated by ferri/ferrocyanide as a redox mediator, and showed reliable sensing performance. The paper-based sensors readily allow for the determination of pyocyanin in bacterial cultures with high reproducibility, achieving a limit of detection of 95 nM and a sensitivity of 4.30 μA/μM in standard culture media. Compared to the similar commercial ceramic based sensors, it is a 2.3-fold enhanced performance. The simple in-house fabrication of sensors for pyocyanin quantification allows researchers to understand in vitro adaptation of P. aeruginosa infections via rapid screenings of bacterial cultures that otherwise are expensive and time-consuming