Patrick Griss

Micromachined electrodes for biopotential measurements

We describe the microfabrication, packaging and testing of a micromachined dry biopotential electrode, (i.e., where electrolytic gel is not required). It consists of an array of micro-dimensioned, very sharp spikes, (i.e., needles) designed for penetration of human skin which circumvent high impedance problems associated with layers of the outer skin. The spikes are etched in silicon by deep reactive ion etching and are subsequently covered with a silver-silverchloride (Ag-AgCl) double layer. The electrode-skin-electrode impedance of dry spiked electrodes having a size of 4/spl times/4 mm/sup 2/ is reduced compared to standard electrodes using electrolytic gel and having a comparable size. Recorded low amplitude biopotentials resulting from the activity of the brain, (i.e., EEG signals) are of high quality, even for spiked electrodes as small as 2/spl times/2 mm/sup 2/. The spiked electrode offers a promising alternative to standard electrodes in biomedical applications and is of interest in research of new biomedical methods.

Characterization of micromachined spiked biopotential electrodes

We present the characterization of dry spiked biopotential electrodes and test their suitability to be used in anesthesia monitoring systems based on the measurement of electroencephalographic signals. The spiked electrode consists of an array of microneedles penetrating the outer skin layers. We found a significant dependency of the electrode-skin-electrode impedance (ESEI) on the electrode size (i.e., the number of spikes) and the coating material of the spikes. Electrodes larger than 3/spl times/3 mm/sup 2/ coated with Ag-AgCl have sufficiently low ESEI to be well suited for electroencephalograph (EEG) recordings. The maximum measured ESEI was 4.24 k/spl Omega/ and 87 k/spl Omega/, at 1 kHz and 0.6 Hz, respectively. The minimum ESEI was 0.65 k/spl Omega/ an 16 k/spl Omega/, at the same frequencies. The ESEI of spiked electrodes is stable over an extended period of time. The arithmetic mean of the generated DC offset voltage is 11.8 mV immediately after application on the skin and 9.8 mV after 20-30 min. A spectral study of the generated potential difference revealed that the AC part was unstable at frequencies below approximately 0.8 Hz. Thus, the signal does not interfere with a number of clinical applications using real-time EEG. Comparing raw EEG recordings of the spiked electrode with commercial Zipprep electrodes showed that both signals were similar. Due to the mechanical strength of the silicon microneedles and the fact that neither skin preparation nor electrolytic gel is required, use of the spiked electrode is convenient. The spiked electrode is very comfortable for the patient.

Painless Drug Delivery Through Microneedle-Based Transdermal Patches Featuring Active Infusion

This paper presents the first microneedle-based transdermal patch with integrated active dispensing functionality. The electrically controlled system consists of a low-cost dosing and actuation unit capable of controlled release of liquid in the microliter range at low flow-rates and minimally invasive, side-opened, microneedles. The system was successfully tested in vivo by insulin administration to diabetic rats. Active infusion of insulin at 2 mul/h was compared to passive, diffusion-driven, delivery. Continuous active infusion caused significantly higher insulin concentrations in blood plasma. After a 3-h delivery period, the insulin concentration was five times larger compared to passive delivery. Consistent with insulin concentrations, actively administered insulin resulted in a significant decrease of blood glucose levels. Additionally, insertion and liquid injection was verified on human skin. This study shows the feasibility of a patch-like system with on-board liquid storage and dispensing capability. The proposed device represents a first step towards painless and convenient administration of macromolecular drugs such as insulin or vaccines.

Penetration-Enhanced Ultrasharp Microneedles and Prediction on Skin Interaction for Efficient Transdermal Drug Delivery

This paper presents penetration-enhanced hollow microneedles and an analysis on the biomechanical interaction between microneedles and skin tissue. The aim of this paper is to fabricate microneedles that reliably penetrate the skin tissue without using penetration enhancers or special insertion tools that were used in the previous studies. The microneedles are made of silicon and feature ultrasharp tips and side openings. The microneedle chips were experimentally tested in vivo by injection of dye markers. To further investigate the penetration, the insertion progression and the insertion force were monitored by measuring the electrical impedance between microneedles and a counter electrode on the skin. The microneedle design was also tested using a novel simulation approach and compared to other previously published microneedle designs. The purpose of this specific part of the paper was to investigate the interaction mechanisms between a microneedle and the skin tissue. This investigation is used to predict how the skin deforms upon insertion and how microneedles can be used to create a leak-free liquid delivery into the skin. The fabricated microneedles successfully penetrated dry living human skin at all the tested sites. The insertion characteristic of the microneedle was superior to an earlier presented type, and the insertion force of a single microneedle was estimated to be below 10 mN. This low insertion force represents a significant improvement to earlier reported results and potentially allows a microneedle array with hundreds of needles to be inserted into tissue by hand.

Hydrophobic valves of plasma deposited octafluorocyclobutane in DRIE channels

The suitability of using octafluorocyclobutane (C4F8) patches as hydrophobic valves in microfluidic biochemical applications has been shown. A technique has been developed to generate lithographica ...

Development of micromachined hollow tips for protein analysis based on nanoelectrospray ionization mass spectrometry

Two novel types of micromachined nanoelectrospray emitter tips have been designed, fabricated and tested. The fabrication method of the hollow tips is based on a self-aligning deep reactive ion etch process. The tips consist of either silicon dioxide or silicon and feature orifice diameters of 10 and 18 μm, respectively. The geometrical characteristics of both emitter types are favorable for the generation of stable electrospray ionization, i.e. wetting of the tip shaft is avoided and the base of the Taylor cone is limited to the diameter of the orifice. A silicon dioxide tip was operated in a bench top setup to visually evaluate the electrospray. Both types of tips were also successfully used for the analysis of an insulin sample in an ion trap mass spectrometer.

Low-temperature wafer-level transfer bonding

In this paper, we present a new wafer-level transfer bonding technology. The technology can be used to transfer devices or films from one substrate wafer (sacrificial device wafer) to another substrate wafer (target wafer). The transfer bonding technology includes only low-temperature processes; thus, it is compatible with integrated circuits. The process flow consists of low-temperature adhesive bonding followed by sacrificially thinning of the device wafer. The transferred devices/films can be electrically interconnected to the target wafer (e.g., a CMOS wafer) if required. We present three example devices for which we have used the transfer bonding technology. The examples include two polycrystalline silicon structures and a test device for temperature coefficient of resistance measurements of thin-film materials. One of the main advantages of the new transfer bonding technology is that transducers and integrated circuits can be independently processed and optimized on different wafers before integrating the transducers on the integrated circuit wafer. Thus, the transducers can be made of, e.g., monocrystalline silicon or other high-temperature annealed, high-performance materials. Wafer-level transfer bonding can be a competitive alternative to flip-chip bonding, especially for thin-film devices with small feature sizes and when small electrical interconnections (<3/spl times/3 /spl mu/m/sup 2/) between the devices and the target wafer are required.

Novel, side opened out-of-plane microneedles for microfluidic transdermal interfacing

We present the first hollow out of wafer plane silicon microneedles that have openings in the shaft rather than having an orifice at the tip. These structures are suited for transdermal microfluidic applications, e.g. drug- or vaccine delivery. The developed deep reactive ion etching (DRIE) process allows fabrication of two dimensional, mechanically highly resistant needle arrays offering low resistance to liquid flows and offering a large exposure area between the fluid and the tissue. The presented process does not require much wafer handling and only two photolithography steps are needed. Using this chip in a typical application, e.g. vaccine delivery, a 100 /spl mu/l volume of aqueous fluid injected through a chip of 3/spl times/3 mm/sup 2/ in 2s would cause a pressure drop of less than 2kPa. The presented needles are approximately 210 /spl mu/m long.

Spiked biopotential electrodes

We describe the microfabrication, packaging and testing of a dry biopotential electrode (i.e. electrolytic gel is not required), The electrode consists of an array of micro-dimensioned, very sharp spikes (i.e. needles) designed for penetration of human skin which circumvents high impedance problems associated with layers of the outer skin. Deep reactive ion etching (DRIE) technology was used to fabricate the spikes. The main advantages of these electrodes include a fast and uncomplicated application procedure, low electrode-skin-electrode impedance (lower than standard electrodes), and comfortable use. The spiked electrode offers a promising alternative to standard electrodes in biomedical applications (i.e. monitoring EEG signals) and is of interest in research of new biomedical methods.

A method for tapered deep reactive ion etching using a modified Bosch process

This paper presents a method for etching tapered sidewalls in silicon using deep reactive ion etching. The method is based on consecutive switching between anisotropic etching using the Bosch proce ...