State of the Art of Micromachining

In this paper the possibilities of focused ion beam (FIB) applications in microsystem technology are reviewed. After an introduction to the technology and the operating principles of FIB, two classes of applications are described. First the subject of FIB for microsystem technology inspection, metrology and failure analysis is outlined. A procedure for cross sectioning on samples is presented, as well as some examples of how this technique can be applied to study processing results. The second part of the paper is on the use of FIB as a tool for maskless micromachining. Both subtractive (etching) and additive (deposition) techniques are discussed, as well as the combination of FIB implantation of silicon with subsequent wet etching. We will show the possibility to fabricate three-dimensional structures on a micrometre scale, and give examples of recent realizations thereof.

/pdf/a-review-of-focused-ion-beam-applications-in-microsystem-3e1lkuepck.pdf

A review of focused ion beam applications in microsystem technology

Development of miniaturized devices that enable rapid and direct analysis of the specific binding of small molecules to proteins could be of substantial importance to the discovery of and screening for new drug molecules. Here, we report highly sensitive and label-free direct electrical detection of small-molecule inhibitors of ATP binding to Abl by using silicon nanowire field-effect transistor devices. Abl, which is a protein tyrosine kinase whose constitutive activity is responsible for chronic myelogenous leukemia, was covalently linked to the surfaces of silicon nanowires within microfluidic channels to create active electrical devices. Concentration-dependent binding of ATP and concentration-dependent inhibition of ATP binding by the competitive small-molecule antagonist STI-571 (Gleevec) were assessed by monitoring the nanowire conductance. In addition, concentration-dependent inhibition of ATP binding was examined for four additional small molecules, including reported and previously unreported inhibitors. These studies demonstrate that the silicon nanowire devices can readily and rapidly distinguish the affinities of distinct small-molecule inhibitors and, thus, could serve as a technology platform for drug discovery.

/pdf/label-free-detection-of-small-molecule-protein-interactions-437kpu1ks7.pdf

Label-free detection of small-molecule–protein interactions by using nanowire nanosensors

Pull-in instability as an inherently nonlinear and crucial effect continues to become increasingly important for the design of electrostatic MEMS and NEMS devices and ever more interesting scientifically. This review reports not only the overview of the pull-in phenomenon in electrostatically actuated MEMS and NEMS devices, but also the physical principles that have enabled fundamental insights into the pull-in instability as well as pull-in induced failures. Pull-in governing equations and conditions to characterize and predict the static, dynamic and resonant pull-in behaviors are summarized. Specifically, we have described and discussed on various state-of-the-art approaches for extending the travel range, controlling the pull-in instability and further enhancing the performance of MEMS and NEMS devices with electrostatic actuation and sensing. A number of recent activities and achievements methods for control of torsional electrostatic micromirrors are introduced. The on-going development in pull-in applications that are being used to develop a fundamental understanding of pull-in instability from negative to positive influences is included and highlighted. Future research trends and challenges are further outlined.

Electrostatic pull-in instability in MEMS/NEMS: A review

We introduce a new economic, convenient and general assay principle based on the reversible interaction of water-soluble macrocycles and fluorescent dyes. We show that amino acid decarboxylase activity can be continuously monitored by measuring changes in fluorescence, which result from the competition of the enzymatic product and the dye for forming a complex with a cucurbituril or calixarene macrocycle. The new assay provides a complementary method to the use of antibodies, radioactive markers and labeled substrates.

Label-free continuous enzyme assays with macrocycle-fluorescent dye complexes.

We report the fabrication of enthalpy arrays and their use to detect molecular interactions, including protein–ligand binding, enzymatic turnover, and mitochondrial respiration. Enthalpy arrays provide a universal assay methodology with no need for specific assay development such as fluorescent labeling or immobilization of reagents, which can adversely affect the interaction. Microscale technology enables the fabrication of 96-detector enthalpy arrays on large substrates. The reduction in scale results in large decreases in both the sample quantity and the measurement time compared with conventional microcalorimetry. We demonstrate the utility of the enthalpy arrays by showing measurements for two protein–ligand binding interactions (RNase A + cytidine 2′-monophosphate and streptavidin + biotin), phosphorylation of glucose by hexokinase, and respiration of mitochondria in the presence of 2,4-dinitrophenol uncoupler.

https://www.pnas.org/content/pnas/101/26/9517.full.pdf

Enthalpy arrays

A novel external electrode concept is introduced and compared with the conventional and often used parallel plate electrode scheme for the electrostatic actuation of micro-electromechanical devices. In contrast to conventional parallel plate actuation, the presented external electrode configuration allows controlled operation of electrostatic actuators over their entire range of motion by avoiding electrostatic instability. The test vehicle for studying deflection versus voltage is a cantilevered beam with a free end, i.e. the worst-case scenario from a stability standpoint. Modeling and fabrication of test devices is discussed and experimental results are presented.

https://iopscience.iop.org/article/10.1088/0960-1317/14/4/003/pdf

A novel external electrode configuration for the electrostatic actuation of MEMS based devices

Enthalpy array analysis of enzymatic and binding reactions.

A microsystem for wireless long-term measurement of the intraocular pressure is presented. The sensing element is a novel distributed parallel-resonant inductive-capacative circuit, with a pressure-dependent resonance frequency. This circuit is based upon a twofold on-chip deposited inductor. The high Q inductor is deposited by electrodeposition of copper on a micromachined chip incorporating a pressure-sensitive diaphragm. Test structures were fabricated and characterized. Q factors of 30 at 45 MHz and inductance values of 0.4 µH are obtained for 3×3 mm2 structures.

https://iopscience.iop.org/article/10.1088/0960-1317/10/2/305/pdf

Electrodeposited copper inductors for intraocular pressure telemetry

This paper reports an extremely miniaturized pressure sensor. In its smallest version, the sensor’s active area is a mere 10 μm ×1  μm. The sensor’s working principle is that of Pirani-type vacuum sensors. However, unlike most Pirani sensors, the working range of the device is around atmospheric pressure. The NanoPirani is fabricated exclusively by a combination of focused ion beam (FIB) deposition and milling. FIB fabrication enables rapid prototyping of this type of surface micromachined devices, as well as flawless integration with electronics. Besides the fabrication sequence, the first experimental results are presented.

Dirk De Bruyker

Papers

Enthalpy arrays

A novel external electrode configuration for the electrostatic actuation of MEMS based devices

Enthalpy array analysis of enzymatic and binding reactions.

Electrodeposited copper inductors for intraocular pressure telemetry

The NanoPirani—an extremely miniaturized pressure sensor fabricated by focused ion beam rapid prototyping