Pedro Ortiz

Biomolecule Patterning on Analytical Devices: A Microfabrication-Compatible Approach

The present work describes a methodology for patterning biomolecules on silicon-based analytical devices that reconciles 3-D biological functionalization with standard resist lift-off techniques. Unlike classic sol-gel approaches in which the biomolecule of interest is introduced within the sol mixture, a two-stage scenario has been developed. It consists first of patterning micrometer/submicrometer polycondensate scaffold structures, using classic microfabrication tools, that are then loaded with native biomolecules via a second simple incubation step under biologically friendly environmental conditions. The common compatibility issue between the biological and microfabrication worlds has been circumvented because native recognition biomolecules can be introduced into the host scaffold downstream from all compatibility issues. The scaffold can be generated on any silicon substrate via the polycondensation of aminosilane, namely, aminopropyltriethoxy silane (APTES), under conditions that are fully compatible with resist mask lithography. The scaffold porosity and high primary amine content allow proteins and nucleic acid sequences to penetrate the polycondensate and to interact strongly, thus giving rise to micrometer/submicrometer 3-D structures exhibiting high biological activity. The integration of such a biopatterning approach in the microfabrication process of silicon analytical devices has been demonstrated via the successful completion of immunoassays and nucleic acid assays.

Issues associated with scaling up production of a lab demonstrated MEMS mass sensor

This work reports on the development of a lab demonstrated resonant mass sensor towards mid-size production. The issues associated with scaling-up production of the microfabricated chip are discussed with particular focus on yield and device reproducibility, as well as the constraints imposed on the design and manufacturing of the device when packaging and integration must be taken into account. Issues of modal alignment and ambient operational pressure are discussed. Fabricated devices show a 4.81?Hz pg?1?mass sensitivity with a temperature sensitivity of typically 10?Hz ?C?1.

Electronic Detection Strategies for a MEMS-Based Biosensor

This work reports on the development of control electronics for a resonant mode biosensor. The laboratory demonstrated sensor initially showed a signal-to-noise ratio of -100 dB. With the application of half-frequency drive, frequency down conversion, appropriate filtering, and digital signal processing, a cost-effective electronic solution demonstrated a signal-to-noise ratio of +30 dB. This paper highlights important aspects in the design of integrated solutions to microelectromechanical systems-based sensors.

An electrostatically actuated cantilever device capable of accurately calibrating the cantilever on-chip for AFM-like applications

We present the principle of an electrostatically actuated cantilever device that can calibrate the cantilever stiffness on-chip with uncertainties in the range of ±5%. The calibration procedure is quick, simple and non-destructive. The device can be fabricated using routine micromachining techniques and be easily made compatible with commercially available atomic force microscopes (AFMs). The electrostatic actuation makes the device quite versatile. In addition to the usual AFM-like applications, the device can also be used for mass-sensing applications as well as an effective interfacial force microscope.

A hybrid microfluidic system for cancer diagnosis based on MEMS biosensors

A microfluidic system for cancer diagnosis based around a core MEMS biosensor technology is presented in this paper. The principle of the MEMS biosensor is introduced and the functionalisation strategy for cancer marker recognition is described. In addition, the successful packaging and integration of functional MEMS biosensor devices are reported herein. This ongoing work represents one of the first hybrid systems to integrate a PCB packaged silicon MEMS device into a disposable microfluidic cartridge.

Packaging of a silicon-based Biochip

We present a sophisticated method for the packaging of a micro-electro-mechanical biochip, which leaves the sensitive surface area of the chip uncovered to allow for direct contact to aqueous environment. Together with adequate integration in a fluidic cartridge, the packaging method allows for the realization of a lab-on-chip (LOC). A fluidic interface to the cartridge is provided as well as electrical interfaces to the biochip electronics located in a readout instrument. The biochip features a central membrane and electrodes, both located in the central chip area, and bond pads distributed along the rim of the chip. The packaging method ensures a hermetic separation between the membrane sensing area interfaced to liquids and the bond pad area. Challenging was the fact that both, the freely moving membrane and the bond pads for electrical interconnection are positioned very close to each other on the same chip surface area. We mounted the biochip into a recess of a rigid printed circuit board and electrically connected it to the latter with a proprietary MicroFlex Interconnection (MFI) technology. A customized coating method using a specially shaped silicone casting-mold ensured a very thin, hermetic encapsulation, which left the membrane safe and freely accessible.

Integration of a bioMEMS device into a disposable microfluidic cartridge for medical diagnostics

A microfluidic system for cancer diagnostics based around a core MEMS biosensor technology is presented in this paper. The principle of the MEMS biosensor is introduced and the functionalisation strategy for cancer marker recognition is described. In addition, the successful packaging and integration of functional MEMS biosensor devices are reported herein. This ongoing work represents one of the first hybrid systems to integrate a PCB packaged silicon MEMS device into a disposable microfluidic cartridge.

A hybrid MEMS-based microfluidic system for cancer diagnosis

A microfluidic system for cancer diagnosis based around a core MEMS biosensor technology is presented in this paper. The principle of the MEMS biosensor is introduced and the functionalisation strategy for cancer marker recognition is described. In addition, the successful packaging and integration of functional MEMS biosensor devices are reported herein. This ongoing work represents one of the first hybrid systems to integrate a PCB packaged silicon MEMS device into a disposable microfluidic cartridge.

Accurate Surface-to-Bulk Feature Alignment and Feature Size Preservation During Double-Sided Wafer Processing Using

An accurate alignment of surface-to-bulk features (within ±2 μm) during a double-sided silicon wafer processing can be extremely difficult. This is due to a combination of mask misalignment errors and unreliability of bulk etching techniques in translating the bulk feature shapes down to the surface side. In this paper, we present a fabrication process for an electrostatically actuated cantilever device where an accurate surface-to-bulk feature alignment is imperative to the operation of the device. The fabrication process compensates for the bulk etch-induced feature size variation and mask misalignment errors using a combination of self-aligning features and C4F8 plasma polymer passivation.

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The present work describes a methodology for patterning biomolecules on silicon analytical devices, such as novel Bio-MEMS or conventional biosensors, that reconciles three-dimensional (3-D) biological functionalisation with standard resist lift-off techniques. Unlike classic sol-gel approaches in which the biomolecule of interest is introduced within the sol mixture, a two-stage scenario has been developed. It consists firstly of patterning micron scale polycondensate scaffold structures - using classic microfabrication tools - which are then loaded with native biomolecules via a second simple incubation step under biologically-friendly environmental conditions. The common compatibility issue between the biological and microfabrication worlds has been circumvented since native recognition biomolecules can be introduced into the host scaffolds downstream of all compatibility issues. The scaffolds can be generated on any silicon substrate via polycondensation of aminosilane - namely aminopropyltriethoxy silane (APTES) - under conditions that are fully compatible with resist mask lithography. The scaffold porosity and high primary amine content allow proteins and nucleic acid sequences to penetrate the polycondensate and to interact strongly, thus giving rise to micron/sub-micron 3-D structures exhibiting high biological activity. The integration of such a bio-patterning approach in the microfabrication process of analytical devices has been demonstrated via the successful biofunctionalisation with recognition antibodies and/or nucleic acid sequences of MEMS circular diaphragm resonator (CDR) sensor patterns.