Adaptive finite element eye model for the compensation of biometric influences on acoustic tonometry.

BACKGROUND AND OBJECTIVE: Glaucoma is currently a major cause for irreversible blindness worldwide. A risk factor and the only therapeutic control parameter is the intraocular pressure (IOP). The IOP is determined with tonometers, whose measurements are inevitably influenced by the geometry of the eye. Even though the corneal mechanics have been investigated to improve accuracy of Goldmann and air pulse tonometry, influences of geometric properties of the eye on an acoustic self-tonometer approach are still unresolved. METHODS: In order to understand and compensate for measurement deviations resulting from the geometric uniqueness of eyes, a finite element eye model is designed that considers all relevant eye components and is adjustable to all physiological shapes of the human eye. RESULTS: The general IOP-dependent behavior of the eye model is validated by laboratory measurements on porcine eyes. The difference between simulation and measurement is below 8 µm for IOP levels from 5 to 40 mmHg. The adaptive eye model is then used to quantify systematic uncertainty contributions of a variation of eye length and central corneal thickness based on input statistics of a clinical trial series. The adaptive eye model provides the required relation between biometric eye parameters and the corneal deflection amplitude, which here is the measured quantity to trace back to the IOP. Implementing the relations provided by the eye model in a Gaussian uncertainty propagation calculation now allows the quantification of the uncertainty contributions of the biometric parameters on the overall measurement uncertainty of the acoustic self-tonometer. As a result, a systematic uncertainty contribution resulting from deviations in eye length dominate stochastic deviations of the sensor equipment by a factor of 3.5. CONCLUSION: As perspective, the proposed adaptive eye model provides the basis to compensate for systematic deviations of (but not only) the acoustic self-tonometer.

Results of First In Vivo Trial of an Acoustic Self-Tonometer.

Purpose: Glaucoma is the world's most common cause of irreversible blindness, which makes early diagnosis, with the goal of preserving vision, essential. The current medical intervention is to reduce intraocular pressure (IOP) to slow down progression of the disease. The main goal of this study was to test a novel handheld acoustic self-tonometer on humans. Methods: A sound pressure pulse generated by a loudspeaker causes the eye to vibrate. A pressure chamber is placed on the human orbit to form a coupled system comprised of the patient's eye, the enclosed air, and the loudspeaker. A displacement sensor in front of the loudspeaker membrane allows the dynamic behavior of the entire system to be detected. Results: For this clinical trial series, a prototype of the acoustic self-tonometer principle was applied. The resulting membrane oscillation data showed sensitivity of patient IOP, but direct allocation of the measured damping and frequency to the IOP was not significant. For this reason, an artificial neural network was used to find relationships among the subjects' biometric eye parameters in combination with the self-tonometer data for the IOP reference. An expanded measurement uncertainty (kp = 2) equal to 6.53 mm Hg was determined for the self-tonometer in a Bland-Altman analysis using Goldmann applanation tonometer reference measurements. Conclusions: The usability and success rate of producing valid measurement values with the device during self-measurements by test subjects was nearly 92%. The cross-sensitivities observed require compensation in a possible redesign phase to reduce the measurement uncertainty by at least 25% to the maximum of 5 mm Hg required to seek medical device approval. Translational Relevance: Building on successful laboratory experiments with pig eyes, this article reports the results of testing the acoustic tonometer on humans.

Methodical Approach for Determining the Length of Drill Channels in Osteosynthesis.

In order to fix a fracture in osteosynthesis, it is necessary to attach screws bicortically to the bone. The length of the screws must be selected correctly in 1-mm increments: otherwise, injury to the surrounding tissue structure or insufficient fixation will result. The drill channel length can only be determined preoperatively to a limited extent and with insufficient accuracy and is therefore determined intraoperatively with a mechanical caliper gauge. This length determination is error-prone, which often leads to a false screw selection and at the same time to considerable complications in the healing process. A novel approach based on a sensory drive train was pursued, with which all mechanical drilling parameters were recorded and evaluated in combination with a length measurement that allows for determining the drill channel length. In order to overcome the limitations of previous drill concepts, a precise length measurement of the drill channel was introduced. The amplitude of a stimulated linear oscillation of the drill was monitored for drilling channel length measurements in order to reliably detect the beginning of the drilling process. The method provides the information required for handheld drilling without the limitation of constant drilling parameters. With initial results from laboratory tests with pig bones, the measurement method for the drill channel length has been validated on a test bench of the drilling machine. With the laboratory tests, a measurement uncertainty of 0.3 mm was achieved, so screws with a 1-mm step width can be reliably selected.

Optical measurement of the corneal oscillation for the determination of the intraocular pressure.

Motivation Glaucoma is currently the most common irreversible cause of blindness worldwide. A significant risk factor is an individually increased intraocular pressure (IOP). A precise measurement method is needed to determine the IOP in order to support the diagnosis of the disease and to monitor the outcome of the IOP reduction as a medical intervention. A handheld device is under development with which the patient can perform self-measurements outside the clinical environment. Method For the measurement principle of the self-tonometer the eye is acoustically excited to oscillate, which is analyzed and attributed to the present IOP. In order to detect the corneal oscillation, an optical sensor is required which meets the demands of a compact, battery driven self-tonometer. A combination of an infrared diode and a phototransistor provides a high-resolution measurement of the corneal oscillation in the range of 10 µm-150 µm, which is compared to a reference sensor in the context of this study. By means of an angular arrangement of the emitter and the detector, the degree of reflected radiation of the cornea can be increased, allowing a measurement with a high signal-to-noise ratio. Results By adjusting the angle of incidence between the detector and the emitter, the signal-to-noise ratio was improved by 40 dB which now allows reasonable measurements of the corneal oscillation. For low amplitudes (10 µm) the signal-to-noise ratio is 10% higher than that of the commercial reference sensor. On the basis of amplitude variations at different IOP levels, the estimated standard uncertainty amounts to <0.5 mm Hg in the physiological pressure range with the proposed measuring approach. Conclusion With a compact and cost-effective approach, that suits the requirements for a handheld self-tonometer, the corneal oscillation can be detected with high temporal resolution. The cross-sensitivity of the sensor concept concerning a distance variation can be reduced by adding a distance sensor. Existing systematic influences of corneal biomechanics will be integrated in the sensor concept as a consecutive step.

Pink bacteria-Production of the pink chromophore phycoerythrobilin with Escherichia coli.

Phycoerythrobilin (PEB) is an open-chain tetrapyrrole derived from heme and plays an important role as light-harvesting pigment in the phycobiliproteins of cyanobacteria and red algae. Furthermore, PEB can also function as an antioxidant with potential use as a natural acid stable food colorant. PEB is not commercially available and large, pure quantities can only be obtained by laborious methanolysis of red algae followed by liquid chromatography. Here we describe an improved method for high yield production and purification of PEB in Escherichia coli via heterologous expression where the two required enzymes heme oxygenase and PEB synthase subsequently convert the substrate heme provided by the host cell. Experiments in shaking flasks resulted in the highest product yield of 680.23 ±â€¯42.75 µg PEB per g cell dry weight, by induction with 0.1 mM IPTG. Scale-up to batch-operated fermentation in a 2 L bioreactor reached product concentrations up to 5.02 mg PEB L-1 by adjustment of aeration, induction time, media composition and supplementation of precursors. A further approach included separation of PEB from developed foam above the culture. This enabled continuous product collection during cultivation and simplified product purification. Produced PEB was validated via UV-vis spectroscopy, high pressure liquid chromatography and mass spectrometry.

Acoustic tonometry: feasibility study of a new principle of intraocular pressure measurement.

PURPOSE: An accurate measurement of intraocular pressure (IOP) is still essential for detecting, following-up, and treating glaucoma. The objective of the interdisciplinary project GlauPhon was to prove a new noncontact tonometry principle that analyzes the acoustic oscillation of the eye. METHOD: Three enucleated porcine eyes were infused via the optic nerve with a saline solution. The IOP was adjusted by varying the height of the infusion bottle. A speaker closed one end of a cylindrical pressure chamber and an eye was fixed to the other side. A PC sound card induced the speaker to oscillate by generating a rectangular signal (20 Hz). A pressure sensor recorded the oscillating pressure within the chamber. For each IOP a calculation was performed that characterizes the attenuation profile. RESULTS: Each series of measurements revealed an evident dependency between the amplitude difference and the IOP. The highest signal belonged to low IOP levels and it decreased with increasing IOP. The correlation of the mean acoustical signal with the given IOP showed a highly significant correlation coefficient (r=-0.98). As a result, the measured oscillation parameters are strongly dependent on the exerted IOPs. CONCLUSIONS: The experiments verified the presumed relation between the acoustic oscillation of the eye and the IOP. Nevertheless, further developments are necessary for converting the oscillation parameters into reliable IOP values, to construct a tonometry device for clinical trials.