Ash M. Parameswaran

Detection and isolation of circulating tumor cells: Principles and methods

Efforts to improve the clinical management of several cancers include finding better methods for the quantitative and qualitative analysis of circulating tumor cells (CTCs). However, detection and isolation of CTCs from the blood circulation is not a trivial task given their scarcity and the lack of reliable markers to identify these cells. With a variety of emerging technologies, a thorough review of the exploited principles and techniques as well as the trends observed in the development of these technologies can assist researchers to recognize the potential improvements and alternative approaches. To help better understand the related biological concepts, a simplified framework explaining cancer formation and its spread to other organs as well as how CTCs contribute to this process has been presented first. Then, based on their basic working-principles, the existing methods for detection and isolation of CTCs have been classified and reviewed as nucleic acid-based, physical properties-based and antibody-based methods. The review of literature suggests that antibody-based methods, particularly in conjunction with a microfluidic lab-on-a-chip setting, offer the highest overall performance for detection and isolation of CTCs. Further biological and engineering-related research is required to improve the existing methods. These include finding more specific markers for CTCs as well as enhancing the throughput, sensitivity, and analytic functionality of current devices.

Monolithically fabricated polymermems 3-axis thermal accelerometers designed for automated wirebonder assembly

This paper reports on two novel 3-axis thermal accelerometers based on different mechanical structures that are fabricated using polyimide PI-2611, and assembled using a standard wire-bonder. One accelerometer design has an un-amplified linear DC sensitivity of plusmn45 muV/g, plusmn60 muV/g, and plusmn35 muV/g on the X, Y, and Z axes respectively. The second design has a sensitivity of plusmn17 muV/g, plusmn8.5 muV/g, and plusmn14 muV/g respectively. Both accelerometers are assembled by applying a lateral push to each of the out-of-plane parts using an unmodified wire-bonder. This paper will detail the fabrication, design, assembly, and functional results of the two 3-axis thermal accelerometer designs.

Fabrication of affordable metallic microstructures by electroplating and photoresist molds

Electroforming processes such as electroplating was used in conjunction with photoresist mold to fabricate surface and substrate micromachined structure. Gold, gold alloys and nickel and nickel-iron alloys were used as structural material in this technique. In case of surface micromachining free standing, cantilevers, bridges and linear and torsional comb drives on silicon substrate were fabricated, whereas in case of substrate micromachined magnetic actuators were fabricated using the above mentioned technology. The thickness of metallic microstructures varied from 8 /spl mu/m to 20 /spl mu/m. This presentation discusses the technology we have developed in our laboratory to fabricate affordable metallic microstructures, as well as presenting functional devices we have built to demonstrate the potential of this technology.

Self-Assembled Monopole Antennas With Arbitrary Shapes and Tilt Angles for System-on-Chip and System-in-Package Applications

The design, fabrication and measurement of self-assembled vertical and oblique monopole antennas, are presented. Vertical on-chip antennas offer advantages over conventional on-chip planar antennas, most notably potentially higher efficiency with associated superior coupling between distant and adjacent ports along the direction of the chip plane. The fabrication method enables lithographical specification of the monopole profile and its sloping angle so that the orientation and shape of monopoles can be controlled. The fabrication process uses SU-8 material and is performed under 200°C and is therefore compatible with many commercial microelectronic fabrication processes such as complementary metal-oxide silicon (CMOS) technology. This allows the integration of the antennas with CMOS front ends and other signal processing stages for communications or sensing.

Solenoid actuator design and modeling with application in engine vibration isolators

This paper investigates the performance of a modified conventional solenoid valve as a low-cost controllable reciprocating force actuator. The applied modifications include adding a spring for plunger return mechanism, applying a bias current for pre-compression of the spring, and minor machining of the plunger rod. Potentially, this actuator can be employed in many applications, e.g. active noise and vibration control systems. A mathematical model of the actuator is given using the fundamental electromagnetic relationships. This model identifies the transfer function between the applied current and the output force. An experimental analysis in the frequency domain is conducted to obtain the current/force transfer function and validate the mathematical model. It is shown that in the stroke range of interest, the nonlinear analytical model of this actuator can be well estimated by a linear model. To investigate the performance of the actuator in a real application, this actuator is installed and tested in an active engine mount prototype. The analytical model of this engine mount is modified to include the actuator. The simulation result indicates that the stiffness and damping of this mount is tunable by controlling the input current to the actuator. The experimental results are also in close agreement with the simulations.

Isopropanol/water as a developer for poly(dimethylglutarimide)

Poly(dimethylglutarimide) (PMGI) is a resist that is commonly used in bilayer and trilayer imaging applications. PMGI can be exposed using various radiation sources including deep UV. Currently, there are only two developers for PMGI reported in the literature: tetramethylammonium hydroxide and tetraethylammonium hydroxide. We introduce a new developer for PMGI, a mixture of isopropanol (IPA) and water. Samples were irradiated with deep UV at 254 nm. The IPA/water developer exhibits rapid dissolution of exposed PMGI, of many microns per minute. However, PMGI exhibits high absorption at 254 nm, so the development depth is limited. The depth limit, after a critical dose, increases linearly with the exposure dose.

MEMS mechanical logic units: design and fabrication with micragem and polymumps

We are currently developing basic building blocks for creating digital logic units that are based on mechanical components, which could be used instead of transistors. Transistors, which are based on semiconductors, rely on precisely controlling the conductivity of their constituent materials. However, at low or high temperatures, that control is lost as semiconductors revert to intrinsic behaviour. Also, semiconductors exhibit various complications under ionizing irradiation. We are looking into creating logic units that use electrical signals, but mechanical relays, with technology provided by MEMS. The logic units consist of a mechanical relay with three electrical gates. The mechanical relay is fabricated with metal over insulator and is operated by applying voltage to the gate, which creates an electric force between the gate and a cantilever. The established electric force arches the cantilever, which is shorted to the source, to make a contact with the drain. Since the operation is based on interactions between metal gates, the proposed method does not suffer from the limitations shared by semiconductors. With different input combinations applied to the gates of the device, development of MEMS mechanical logic units is possible, including all of the standard digital gates

Design and development of actuating system for diagnostics application in minimally invasive surgery (MIS)

This paper presents some initial concepts in the design and development of actuating systems based on shape memory alloy for Minimally Invasive Surgery (MIS). Specially the motivation is to design tissue/fluid storage mechanism which can be used to collect samples from the surgical area for further diagnostic procedure. The proposed hybrid design combines passive source of energy with the active source. The passive source is based on the storage of spring energy and the active source is based on utilization of shape memory alloy as a part of switching mechanism. Various design concepts for the switching mechanism are presented combined with the design of their prototypes.

Patterning of PMMA Microfluidic Parts using Screen Printing Process

An inexpensive and rapid micro-fabrication process for producing PMMA microfluidic components has been presented. Our proposed technique takes advantages of commercially available economical technologies such as the silk screen printing and UV patterning of PMMA substrates to produce the microfluidic components. As a demonstration of our proposed technique, we had utilized a homemade deep-UV source, λ=254nm, a silk screen mask made using a local screen-printing shop and Isopropyl alcohol - water mixture (IPA-water) as developer to quickly define the microfluidic patterns. The prototyped devices were successfully bonded, sealed, and the device functionality tested and demonstrated. The screen printing based technique can produce microfluidic channels as small as 50 micrometers quite easily, making this technique the most cost-effective, fairly high precision and at the same time an ultra economical plastic microfluidic components fabrication process reported to date.

Applications for Low Frequency Impedance Analysis Systems

We present methodology and instrumentation used to carry out and log automated multiple electrical impedance measurements using multiplexed control. We also address the issue of measurement error introduced by the instrumentation, and demonstrate how we reduce these effects in our experiments. Finally, we present two potential applications for our automated electrical impedance analysis systems: tissue scanning and mapping via impedance measurements between arrays of electrodes, and materials testing of novel conductive polymer materials.