William Allan Lane

A DNA diagnostic biosensor: development, characterisation and performance

Abstract The aim of this work is to develop a sensor for specific DNA sequences, using non-complex synthetic single-stranded oligonucleotides as a model system. A capacitance-based sensor for the direct detection of DNA sequences is described. Hybridisation of analyte DNA with immobilised DNA on the silicon surface induces charge effects, altering the dielectric properties of the biolayer, and can be detected by the associated change in the measured capacitance. DNA has been immobilised on a silicon electrode either by passive adsorption or covalent coupling via 4-aminobutyldimethylmethoxysilane (4-ABDMMS). The work presented here introduces a colourimetric immunodetection technique for the evaluation of the immobilisation process and describes the electrical characterisation and performance of three silicon-based sequence-specific DNA sensors. These sensors consisted of a standard electrolyte-insulator-semiconductor (EIS) structure with covalently bound probe DNA, a mechanically degraded structure with passively adsorbed probe DNA and a mechanically degraded structure with covalently bound probe DNA. The last device had an improved signal to noise ratio and was, therefore, used to construct a standard curve, revealing a detection limit of 100 pmol DNA. On addition of analyte DNA, there was a decrease in measured capacitance. This response was fast, specific and required no addition of mediators to enhance or amplify the signal. This device can be optimised for the detection of complex sequences.

Application of magnetohydrodynamic actuation to continuous flow chemistryElectronic supplementary information (ESI) available: figures depicting a silicon MHD microreactor, finite element solution for velocity profile in the silicon microreactor annulus, and the effect of MHD actuation conditions on the PCR product previously generated by conventional amplification methods and on the PCR reagents prior to thermocycling by conventional methods. See http://www.rsc.org/suppdata/lc/b2/b206756k/

Continuous flow microreactors with an annular microchannel for cyclical chemical reactions were fabricated by either bulk micromachining in silicon or by rapid prototyping using EPON SU-8. Fluid propulsion in these unusual microchannels was achieved using AC magnetohydrodynamic (MHD) actuation. This integrated micropumping mechanism obviates the use of moving parts by acting locally on the electrolyte, exploiting its inherent conductive nature. Both silicon and SU-8 microreactors were capable of MHD actuation, attaining fluid velocities of the order of 300 microm s(-1) when using a 500 mM KCl electrolyte. The polymerase chain reaction (PCR), a thermocycling process, was chosen as an illustrative example of a cyclical chemistry. Accordingly, temperature zones were provided to enable a thermal cycle during each revolution. With this approach, fluid velocity determines cycle duration. Here, we report device fabrication and performance, a model to accurately describe fluid circulation by MHD actuation, and compatibility issues relating to this approach to chemistry.

The design of thin-film polysilicon resistors for analog IC applications

The authors describe the design of thin LPCVD polysilicon resistors based on their desired electrical performance (sheet resistance, temperature coefficient, voltage nonlinearity, and matching and uniformity). Based on measured data and an understanding of polysilicon carrier transport phenomena, it is shown how resistor processes can be designed for a wide variety of analog IC (integrated circuit) applications, requiring only ion implantation and standard polysilicon deposition and patterning processes. For a +or-500 p.p.m./ degrees C temperature coefficient of resistance range, the available sheet resistance lies between 2400 and 40 Omega /sq. for a polysilicon thickness ranging from 50-600 nm. Matching and nonlinearity (in a 10-V range) to better than 0.06% has been achieved from a process designed as described. Thus it is demonstrated that performance comparable to thin sputtered resistor films can be achieved without the requirement of a long development time and specialized knowledge. >

An enhanced SPICE MOSFET model suitable for analog applications

A MOSFET model optimized for analog circuit simulation is presented and shown to agree with measured device characteristics, especially device output conductance and transconductance, over a wide range of operation. The widely used SPICE Level 3 (MOS3) model equations were utilized as a starting point in the model development process. The enhanced model (NMOD) exhibits smooth and continuous transitions in the weak to strong inversion region, and in the region between linear and saturation modes of device operation. These smooth transitions improve both the models current and conductance prediction accuracy, as well as its convergence properties when used in circuit simulation. This is made possible because a single current equation is utilized for all regions of device operation. The NMOD model accurately characterizes devices over a wide range of geometries, achieving, for example, 1.3% and 4.2% average errors between measured and model I/sub DS/ and gds characteristics, respectively, for a 20/1.3- mu m p-channel device over a 5-V bias range. >

Investigation into immobilisation of lactate oxidase to improve stability

Abstract Lactate oxidase (LOx) is an unstable enzyme. In this work, a variety of immobilisation techniques are investigated in an effort to improve the long-term stability of the enzyme. These include covalent linkage to two membrane types, encapsulation in a BSA gel and four different sol–gel matrices. The enzyme glucose oxidase (GOx) was also immobilised in the same sol–gel matrices. The methods were assessed for both activity and stability of the enzyme and the mechanical rigidity of the matrix. The BSA and sol–gels both formed physically robust enzyme layers. The enzyme retained its activity in the BSA gel for 20 days. Activity of the enzyme was much higher in the sol–gel matrices and remained stable for at least 55 days. Sol–gel processing conditions were also investigated.

MOSFET statistical parameter extraction using multivariate statistics

A methodology for the generation of MOSFET device model parameter sets which reflect measured device performance variations is described and assessed for its accuracy and suitability in predicting actual circuit variations. The proposed scheme is based on the principal component method of multivariate statistical techniques and utilizes Monte Carlo simulations. Comparisons between the predictions of device and circuit characteristics and measured characteristics over a wafer lot are shown and discussed. It is suggested that the techniques used are most suitable for the prediction of the measured distributions of precision analog circuits rather than large digital circuits where 25 or more circuit simulations may be totally unacceptable because of the amount of CPU time required.<<ETX>>

Development and characterisation of a surface micromachined FET pressure sensor on a CMOS process

Abstract This paper presents the development methodology and performance results of a surface micromachined FET pressure sensor integrated into a CMOS process. The working pressure range examined is 15 to 95 psi of absolute pressure. The sensor consists of a polysilicon pillbox structure which forms an evacuated cavity. The polysilicon is the gate electrode of an MOS device created using the cavity as the gate dielectric, deflection of the polysilicon with applied pressure can be sensed as a change in drain current of this MOS device. The finite-element program ANSYS is used to establish suitable values for the area and thickness of the diaphragm and the cavity height. A device simulator is used to predict the performance of the MOS structure for various deflections. The fabrication of the sensor element takes place after the source/drain anneal and before interlayer deposition of an otherwise standard CMOS process. The output current of a fabricated MOS sensor with diaphragm plate length of 75 μm over the range of 15 to 95 psi increased from 70 to 170 μA at a bias of V ds =11 V, V gs =13 V.

An approach for relating model parameter variabilities to process fluctuations

A methodology that makes it possible to link circuit simulator model parameter variations and correlations to disturbances in the IC manufacturing process is presented. An example in which the variabilities among a set of 30 correlated empirical MOSFET model parameters from a 2- mu m CMOS process are represented by the variabilities of just six uncorrelated components with the aid of principal component analysis (PCA) and VARIMAX transformations is described. The derived uncorrelated components are interpreted in terms of the probable process input fluctuations causing them. These independent components may then be utilized to form the basis of realistic worst-case design methodologies or more rigorous statistical design techniques.<<ETX>>

Extraction of MOSFET Parameters Using the Simplex Direct Search Optimization Method

The method of extracting MOSFET model parameters using optimization offers significant advantages over classical methods of extracting model parameters sequentially. Previous work in this field has concentrated on speed of convergence rather than general applicability. Gradient following methods have been applied to this problem but difficulties arise because of parameter redundancy, singularities in the objective function, and the necessity of providing very good initial estimates of the model parameters. These factors can seriously hinder the application of the technique. This paper describes the application of the simplex direct search optimization method to this problem. This algorithm, in wide use for general optimization problems, needs no derivative calculation and has proved highly stable for MOS model parameter extraction. Its basis is described and an example of its use given.

Development of a pH-sensitive ISFET suitable for fabrication in a volume production environment

Abstract Silicon nitride (Si 3 N 4 ) is used extensively as the pH-sensitive surface in ion-sensitive field-effect transistors (ISFETs). However, in order for it to exhibit a Nernstian pH response, a treatment in hydrofluoric acid (HF) is often required immediately prior to use. This article describes a method of increasing the pH sensitivity of Si 3 N 4 by using rapid thermal processing (RTP) techniques. Our investigations show that this is a very controlled method of surface modification. It does not interfere with standard processing techniques and most importantly it eliminates the need for a HF treatment. Thus, it is concluded that RTP of Si 3 N 4 is very suitable for use in a volume production environment and is potentially an effective method of controlling the Si 3 N 4 surface in ISFETs.