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.

[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.

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.

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.

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.

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.

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.

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.

Stimulation and recording from regenerated peripheral nerves through polyimide sieve electrodes.

This paper describes the use of a new polyimide sieve electrode as a chronic neural interface to stimulate and record signals from regenerated peripheral nerves. Flexible thin polyimide electrodes were placed in silicone chambers and implanted between the severed ends of the sciatic nerve in rats. The sieve part of the interface has 281 round via holes of 40 microns diameter, with seven integrated recording-stimulating electrodes arranged around via holes. Axonal regeneration through the via holes was demonstrated by histological and physiological methods over a two to six month post-implantation period in all the rats. The regenerated nerves were organized in fascicles corresponding to the grid pattern of the via holes. Longitudinal sections showed myelinated fibers, with normal appearance and well developed myelin sheath, crossing the via holes. Stimulation of the regenerated nerve through the polyimide electrode evoked distal muscle and nerve responses similar in amplitude to those evoked by nerve stimulation with hook metal electrodes. The polyimide electrodes were useful for recording nerve action potentials in response to electrical stimulation of the distal regenerated nerve, and in response to functional sensory stimulation of several modalities.

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.

Principles of multimodal imaging.

Current medical practice deals with a variety of multimodal information (X-ray film, ultrasound, CT, MR, ECG and EEG, laboratory results, medical records, etc.) Diagnosis and treatment demand an integrated view of this information including the patient's record and history. This paper describes multimodal imaging approaches to such a system with regard to (i) user interface, (ii) data management (including access control), (iii) registration and modality matching based on reference models, and (iv) interface to the modalities.

Intelligent surgical instrument system ISIS. Concept and preliminary experimental application of components and prototypes.

The recent progress in endoscopic surgery, which is highlighted by the complexity of fundoplication, stomach surgery and colorectal surgery, has revealed major restrictions with difficult surgical manipulations. Mobilisation, dissection and suturing techniques are hampered mainly by the limited degrees of freedom of the conventional rigid instruments (translation along and rotation around the longitudinal axis and the limited play in the access channel). The frequent interchange of instruments such as coagulation forceps, scissors and suction-irrigation probe is time-consuming. We have established an interdisciplinary development model with the aim of improving surgical technology, instrument systems, the operation theatre and its environment. Concepts of electronic instrument control and sensoric feedback, and the features of the surgical man-machine-interface are described. The first prototypes of an intelligent steerable instrument system, ISIS, and its optional effectors, e.g. semiautomatic sewing device and multifunctional coagulation instrument, were tested in phantom and animal experiments. System analysis will lead to specially designed operating theatres (minimal invasive surgical operating system MINOS).

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.

Hemodynamic responses in rabbit tenuissimus muscle arterioles during local reduction in perfusion pressure.

Transverse (TR) and terminal (TE) arteriolar diameters and TR pressure were measured in the rabbit tenuissimus muscle during steady state reductions in perfusion pressure. An inflatable occluder was positioned on the abdominal aorta proximal to the bifurcation to alter perfusion pressure. In the control conditions, TEs exhibited highly regular cyclic activity (20 +/- 4 cpm). In contrast, TRs seldom exhibited regular vasomotor activity. Pressure reductions from 76 +/- 1 to 40-50 mm Hg caused no significant change in the observed hemodynamic variables. Reductions below this level caused proportional dilations of TRs and a change in vasomotion pattern of TEs; i.e. the fundamental frequency was unaltered, but periods without vasomotion increased in duration. At an arterial pressure of 30-40 mm Hg, vasomotion in the TEs completely disappeared. Pressure in the distal TR was autoregulated at 40 +/- 4 mm Hg until a threshold (40-50 mm Hg) was reached; thereafter TR pressure decreased in proportion to the arterial pressure decrements. These results suggest that the TRs are the last generation of arterioles involved in the autoregulation of microvascular pressure. Furthermore, the basic frequency and maximal amplitude of vasomotion in TEs are not affected by pressure reductions.