Advanced technologies and devices for inhalational anesthetic drug dosing.

Technological advances in micromechanics, optical sensing, and computing have led to innovative and reliable concepts of precise dosing and sensing of modern volatile anesthetics. Mixing of saturated desflurane flow with fresh gas flow (FGF) requires differential pressure sensing between the two circuits for precise delivery. The medical gas xenon is administered most economically in a closed circuit breathing system. Sensing of xenon in the breathing system is achieved with miniaturized and unique gas detector systems. Innovative sensing principles such as thermal conductivity and sound velocity are applied. The combination of direct injection of volatile anesthetics and low-flow in a closed circuit system requires simultaneous sensing of the inhaled and exhaled gas concentrations. When anesthetic conserving devices are used for sedation with volatile anesthetics, regular gas concentration monitoring is advised. High minimal alveolar concentration (MAC) of some anesthetics and low-flow conditions bear the risk of hypoxic gas delivery. Oxygen sensing based on paramagnetic thermal transduction has become the choice when long lifetime and one-time calibration are required. Compact design of beam splitters, infrared filters, and detectors have led to multiple spectra detector systems that fit in thimble-sized housings. Response times of less than 500 ms allow systems to distinguish inhaled from exhaled gas concentrations. The compact gas detector systems are a prerequisite to provide "quantitative anesthesia" in closed circuit feedback-controlled breathing systems. Advanced anesthesia devices in closed circuit mode employ multiple feedback systems. Multiple feedbacks include controls of volume, concentrations of anesthetics, and concentration of oxygen with a corresponding safety system. In the ideal case, the feedback system delivers precisely what the patient is consuming. In this chapter, we introduce advanced technologies and device concepts for delivering inhalational anesthetic drugs. First, modern vaporizers are described with special attention to the particularities of delivering desflurane. Delivery of xenon is presented, followed by a discussion of direct injection of volatile anesthetics and of a device designed to conserve anesthetic drugs. Next, innovative sensing technologies are presented for reliable control and precise metering of the delivered volatile anesthetics. Finally, we discuss the technical challenges of automatic control in low-flow and closed circuit breathing systems in anesthesia.

Development of a biosensor for E. coli based on a flexural plate wave (FPW) transducer.

To fulfill the need for rapid, cost-effective and sensitive methods for the detection of bacteria in medical diagnostics, food technology, biotechnology and environmental monitoring, a development of a bacterial sensor was initiated. Our approach of a biosensor for E. coli is based on an acousto-gravimetric flexural plate wave (FPW) transducer (gravimetric detection limit of less than 6 ng in a 32 microns thick sensitive layer in aqueous media), and an immunoaffinity layer on the transducer membrane for the molecular recognition of the target bacteria. An intermediate layer of covalently coupled poly (acrylic acid) yielded a major reduction of the non-specific binding to the metal surface. Such a biosensor, using antibodies against E. coli K12 and E. coli 15 outer surface antigens, yielded a detection range of 3.0 x 10(5) to 6.2 x 10(7) cells/ml for samples with the corresponding bacteria. To increase the sensitivity further, an amplification method using microspheres coupled with antibodies against E. coli was tested as a sandwich assay, and up to now a five-fold amplification of the signal has been achieved.

A biohybrid system to interface peripheral nerves after traumatic lesions: design of a high channel sieve electrode.

Peripheral nerve lesions lead to nerve degeneration and flaccid paralysis. The first objective in functional rehabilitation of these diseases should be the preservation of the neuro-muscular junction by biological means and following functional electrical stimulation (FES) may restore some function of the paralyzed limb. The combination of biological cells and technical microdevices to biohybrid systems might become a new approach in neural prosthetics research to preserve skeletal muscle function. In this paper, a microdevice for a biohybrid system to interface peripheral nerves after traumatic lesions is presented. The development of the microprobe design and the fabrication technology is described and first experimental results are given and afterwards discussed. The technical microprobe is designed in a way that meets the most important technical requirements: adaptation to the distal nerve stump, suitability to combine the microstructure with a containment for cells, and integrated microelectrodes as information transducers for cell stimulation and monitoring. Micromachining technologies were applied to fabricate a polyimide-based sieve-like microprobe with 19 substrate-integrated ring electrodes and a distributed counter electrode. Monolithic integration of fixation flaps and a three-dimensional shaping technology led to a device that might be adapted to nerve stumps with neurosurgical sutures in the epineurium. First experimental results of the durability of the shaping technology and electrochemical electrode properties were investigated. The three-dimensional shape remained quite stable after sterilization in an autoclave and chronic implantation. Electrode impedance was below 200 kOmega at 1 kHz which ought to permit recording of signals from nerves sprouting through the sieve holes.

Characterization and optimization of microelectrode arrays for in vivo nerve signal recording and stimulation.

Revealing the complex signal-processing mechanisms and interconnection patterns of the nervous system has long been an intriguing puzzle. As a contribution to its understanding the optimization of the impedance behavior of implantable electrode arrays with via holes is discussed here. Peripheral axons will regenerate through these holes allowing for simultaneous nerve stimulation and signal recording. This approach is part of the ESPRIT project INTER and may eventually lead to devices driving sensory motor prosthesis with closed loop control. In the first set of experiments, micromachined platinum electrode arrays were prepared, characterized and optimized for nerve signal recording. The results of these studies are based on impedance spectroscopy and microscopic techniques. Equivalent circuits were modeled describing formally the electrical response behavior with ohmic resistances between 500 omega and 10 k omega. To attain low impedances for all electrodes on the INTER device, platinum from H2PtCl6 was electrodeposited, and sputter technology as well as electrochemical deposition from H2IrCl6 solution were used to produce thin iridium films. For the former, a lift-off process was established at one of the institutes to generate electrode structures with a line width of 5 microns. As a result in all three cases the electrodes showed almost constant impedances over the entire frequency range (10 Hz-1 kHz), which is relevant for nerve signal recording. In the second set of experiments, electrodes were optimized to allow for nerve stimulation. For this purpose, the charge delivery capacity (CDC) had to be increased and the impedance had to be decreased. Iridium oxide is the material of choice, because its CDC is much higher than the CDC of platinum at 75 microC/cm2 (Ziaie et al., 1991, IEEE Sensors & Actuators Transducers, 6, 124-127). A significant increase of the electrochemically active surface of the electrode structures could be observed by measuring the surface roughness. In first experiments, an activated iridium oxide film was formed with cyclic voltammetry and was evaluated using scanning force microscopy and impedance spectroscopy. The evaluation of the cyclic voltammograms showed a CDC up to 400 mC/cm2 for sputter deposited and oxidatively treated iridium films. Further investigations are directed towards increasing the stability of the iridium oxide electrodes with regard to long-term implants. Parallel experiments aim at the controlled axon adhesion without changing the impedance behavior of the described electrodes.

Towards micro electrode implants: in vitro guidance of rat spinal cord neurites through polyimide sieves by Schwann cells.

Our goal is to develop biohybrid neural microprobe implants with sieve electrodes for external stimulation of co-implanted neurons whose axons penetrate through the holes of electrodes and innervate host targets such as denervated muscle fibers. For evaluation of implants, potential scar formation was imitated in fibroblast-spinal cord co-cultures. In vitro neurite extension through flexible 10-microm thick polyimide sieves was inhibited by co-cultured fibroblasts. In contrast, the neurite penetration of sieves could be greatly stimulated by oriented exposure to Schwann cells. To our knowledge this is the first direct proof that Schwann cells display a guidance effect on spinal cord neurons in vitro. The results pave the way for novel biohybrid neuro-implants and provide means to circumvent the obstacle of inhibitory scar formation.

The Prony spectral line estimation (PSLE) method for the analysis of vascular oscillations.

The Prony spectral line estimation (PSLE) technique is implemented and tested on data consisting of sinusoids mixed with Gaussian noise and on recordings of oscillatory diameter changes (vasomotion) of arterioles. It is concluded that the PSLE method is well suited for the spectrum analysis of short oscillatory diameter records.

Fast and precise positioning of single cells on planar electrode substrates.

For cell biosensors and for studying neural networks using planar electrode substrates, a suitable technique for positioning single cells on electrodes was needed. We reported a new method for fast and efficient positioning of single cells on ring electrodes by controlled suction through holes. We described the microfabrication of electrode substrates with microholes and the cell positioning procedure. L929 cells and Neuro 2A cells could be positioned in parallel without cell damage.

Postural responses of head and foot cutaneous microvascular flow and their sensitivity to bed rest.

To explore the mechanism for facial puffiness, headache, and nasal congestion associated with microgravity and cephalad fluid shifts, the postural responses of the cutaneous microcirculation in the forehead and dorsum of the foot of eight healthy men were studied by changing body position on a tilt table and measuring blood flows with a laser-Doppler flowmeter. Increasing arterial pressure in the feet by moving from a -6 degree head-down tilt to a 60 degrees head-up posture decreased foot cutaneous flow by 46.5 +/- 12.0% (mean +/- S.E.; p less than 0.05). Raising arterial pressure in the head by tilting from the 60 degree head-up to -6 degree head-down posture increased forehead cutaneous flow by 25.5 +/- 7.2% (p less than 0.05). To investigate the possibility that these opposite responses could be modified by simulated microgravity, tilt tests were repeated after 7 d of -6 degrees head-down tilt bed rest. On the 1st and 2nd days after bed rest, flows in the foot were decreased by 69.4 +/- 8.8% and 45.8 +/- 18.7%, respectively, and increased in the head by 39.3 +/- 8.6% and 15.5 +/- 5.9%, respectively. These responses were not significantly different from those recorded before bed rest. Therefore, cutaneous microcirculatory flow in the feet is well regulated to prevent edema when shifting to an upright position, whereas there is less regulation in the head microcirculation. The lack of regulation in the forehead cutaneous microcirculation increases capillary flow, and consequently increases fluid filtration. This phenomenon helps explain the facial edema associated with the stimulated or actual microgravity environment.

Competence Center for Miniaturised Monitoring and Intervention Systems MOTIV.

In the national Competence Center, the whole value chain, from the idea to the development of a product ready for the market, is brought together. MOTIV has underlined three focus point: It wants to improve the therapy and therapy control, to develop intelligent microimplants and to create innovative telematic home healthcare concepts.

[Initial chronic results of flexible sieve electrodes as interface to nerve stumps]. / Erste chronische Ergebnisse von flexiblen Siebelektroden als Schnittstelle zu Nervenstümpfen.

Since more than 20 years, nerve stumps have been interfaced with sieve-like microsystems with integrated electrodes in experimental studies. In most cases, silicone tubes have been assembled on the microsystems to adapt the nerve and deliver a guidance structure for regeneration. Flexible, polyimide-based sieve electrodes with integrated fixation aids have been implanted chronically in an animal model. They have been adapted between the transsected ends of the sciatic nerve of rats and on the proximal stump in an amputation model. First electrophysiological experiments proved the functional reinnervation. Combining embryonic motor neurons with the sieve electrode, we propose a biohybrid system that is under investigation to functionally interface the distal part of a transsected peripheral nerve.

Implantable microsystems. Polyimide-based neuroprostheses for interfacing nerves.

Neuroprostheses are technical devices for functionally interfacing parts of the nervous system. Using micromachining technology and flexible materials for substrate and insulation, miniaturized implants have been fabricated that offer new opportunities to assist those suffering from neurological disorders. This article reviews the technology and discusses potential applications.

Measurement of the dynamics of arteriolar diameter.

The diameter of the arteriolar vessels of the microcirculation undergoes a continuous variation as a consequence of vasomotion. The quantification of this process requires the implementation of spectral analysis techniques that model short data records of a finite number of superposed sinusoidal waveforms. The following techniques were tested with artificially synthetized records and actual data: the fast Fourier transform, the high-resolution autoregressive method, the maximum entropy method, and the Prony Spectral Line Estimator (PSLE). It was found that the PSLE provides the most accurate estimation of the spectral components of the dynamics of diameter changes because it does not require any assumption on the nature of the data outside the interval under analysis.

Responsiveness of microcirculation and local cold vasodilation to capsaicin in the intact and chronically denervated canine tongue.

Lingual blood flow and its distribution were determined at rest and in response to local cooling of the tongue (32 degrees C) in 6 anaesthetized, paralyzed and artificially ventilated dogs before and after two intraarterial (i.a.) injections of capsaicin (2.5 mg) at an interval of about 40 min. In 3 dogs, the same protocol was performed after degeneration of the chorda-lingual and glossopharyngeal nerves due to prior transection. In general the first i.a. injection of capsaicin resulted in a marked and the second injection in a smaller decrease of lingual blood flow. Local cooling of the tongue induced significant increases in lingual blood flow before as well as after capsaicin treatment, regardless of whether sensory innervation was intact or degenerated. In both the untreated and capsaicin treated dogs the increase in lingual blood flow during local cooling of the tongue was solely due to an increase in blood flow through the arteriovenous anastomoses, while blood flow through the capillaries of the mucosa and muscles even decreased. The findings suggest that capsaicin-induced vasoconstriction of the tongue vessels is due to a direct effect on vascular receptors. It is further suggested that cold vasodilatation of the canine tongue is not mediated by axon collaterals releasing substance P. Direct thermal effects on the intramural ganglia and the postganglionic vasomotor efferents innervating the AVAs, or on AVAs basal tone itself are suggested as the underlying mechanism.