Achieving near-zero particle generation by simplicity of design—A compliant-mechanism-based gripper for clean-room environments

Lab Automation facilitates high-throughput processes and improves reproducibility and efficiency while removing human action, primary source of contaminating particles. Handling poses a risk of contamination due to close contact with the objects. We propose a novel gripper (CrocoGrip) relying on compliant mechanisms to reduce the amount of contaminating particles generated by the gripper rather than preventing their emission, the latter being the common approach in current grippers. Using a structured design approach including simplified motion models and Finite Element Methods, we developed a novel gripper that is actuated by linear solenoids and purely relies on deformation for its motion. As a result, abrasive behavior and, therefore, the generation of particles is reduced without the need for additional sealing. We experimentally proved that the number of particles emitted by the CrocoGrip fulfills the demands of ISO14644 class 5. Due to the monolithic design of the CrocoGrip and, as a result, the need for few components, we achieve a simplicity of design, making cleaning, sterilization and maintenance easy, even for nonexperts. Furthermore, all parts but the two solenoids can be sterilized through autoclaving. The gripping is performed by utilizing the deformation energy of the compliant mechanism, making the gripping energy-efficient and safe. By using interchangeable jaws, the CrocoGrip was able to handle a microplate in SBS-standard, a 50 mL Falcon tube, and a Ø60 mm Petri dish using a robotic arm. CrocoGrip exploits the advantages of compliant mechanisms, especially for applications requiring clean-room environments. This approach of CM-based grippers enables an increase in the cleanliness of handling processes without an increase in system complexity of the gripper to facilitate the lab automation of highly sensitive processes, such as in tissue engineering

Robotik trifft auf Tissue-Engineering : Künstliche Gewebe als Therapiekonzept bei Herzinfarkten

Herzkreislauferkrankungen sind die Haupttodesursache weltweit. Wissenschaftler*innen vom Institut für Mechatronische Systeme (imes) arbeiten an mechatronisch unterstützten Therapiemöglichkeiten bei Herzinsuffizienz sowie an der Herstellung von Herzmuskeln für in-vitro Tests. Ziel ist, die Leistungsfähigkeit des Herzens nach einem Infarkt wiederherzustellen

Nova Geminorum 1912 and the Origin of the Idea of Gravitational Lensing

Einstein's early calculations of gravitational lensing, contained in a scratch notebook and dated to the spring of 1912, are reexamined. A hitherto unknown letter by Einstein suggests that he entertained the idea of explaining the phenomenon of new stars by gravitational lensing in the fall of 1915 much more seriously than was previously assumed. A reexamination of the relevant calculations by Einstein shows that, indeed, at least some of them most likely date from early October 1915. But in support of earlier historical interpretation of Einstein's notes, it is argued that the appearance of Nova Geminorum 1912 (DN Gem) in March 1912 may, in fact, provide a relevant context and motivation for Einstein's lensing calculations on the occasion of his first meeting with Erwin Freundlich during a visit in Berlin in April 1912. We also comment on the significance of Einstein's consideration of gravitational lensing in the fall of 1915 for the reconstruction of Einstein's final steps in his path towards general relativity.Comment: 31 p

A software for online monitoring of orientation-compensated forces during CI insertion

The electrode array insertion is a critical point during CI surgery and should be performed as gently as possible to preserve residual hearing. In order to measure occurring forces, an insertion tool with an integrated force sensor and an inertial measurement unit (IM U) is being developed. The weight of the electrode holder and the sensor add an unknown offset to the measured forces, depending on the tool orientation. To address this problem, a software which calculates the orientation-induced error and computes a corrected force was developed. The software was written in C++ using the library Qt 5.12.9. For maximization of the computing frequency, the data acquisition of both sensors and the monitoring was parallelized. An algorithm was developed to calculate the error caused by the electrode holder and sensor. For this purpose both weights were determined in a calibration procedure and merged with the provided IM U data. The evaluation was done in two test series (each n=5) with different initial tool orientations. To this end a stepwise 360° rotation around the horizontal axis was performed, while recording the corrected forces. The developed software allows a computing frequency up to 100 Hz with a latency of 10 ms for the online monitoring of the processed data. The evaluation of the corrected force shows a residual error of 0.347 mN ± 0.325 mN for the first and 0.176 mN ± 1.971 mN for the second test series. With the created algorithm, the impact of the extra weight on the sensor can be almost fully equalized. The highly responsive software offers a new possibility to process insertion forces and provide feedback to surgeons. Determining the influence of the tool orientation on the corrected forces is the subject of future researches

Temporal bone phantom for decoupled cochlear implant electrode insertion force measurement

In research on cochlear implants, preclinical testing of newly developed electrode arrays and surgical tools is an essential procedure, which requires the availability of a suitable testing environment. For this purpose, human temporal bone specimens are most realistic, but their availability is limited and additional parameters such as insertion forces are hardly measurable. Therefore, the aim of this study was to develop a temporal bone phantom with realistic anatomical structures for intracochlear force measurement. The temporal bone was segmented from CBCT data of a human cadaver head. The segmented model was 3D printed with an additional artificial skin layer to enable the simulated use of surgical instruments such as a self-retaining retractor. A mechanically decoupled artificial cochlear model was realistically positioned within the temporal bone and was furthermore attached to a force sensor. The usability of the phantom was evaluated by performing automated EA insertions using an automated hydraulic insertion device. The experiments showed that the insertion forces within the cochlea could be measured without interferences from surrounding structures. Moreover, the artificial skin provided a rigid interface for the insertion tool. The new phantom is a realistic testing and training platform for cochlear implant electrode insertions with the advantage of measureable insertion forces

Core-Shell Capsule Image Segmentation through Deep Learning with Synthetic Training Data

Core-shell capsules (CSC) are a promising approach for 3D cell culture because they overcome the challenges of traditional large-scale cell cultivation techniques used in tissue engineering. Currently, CSC are segmented from microscopic images in a cumbersome manual procedure to evaluate their properties, such as size or complete encapsulation of the core compartment. In this paper, we propose an automated segmentation process of CSC based on an unmodified YOLOv8 instance segmentation model.We train the model exclusively on synthetic CSC images created from 10 manually annotated real images and evaluate its performance using the common Intersection over Union (IoU) metric on a test set consisting of 181 real images. Without modifying the model or tuning the hyperparameters, we achieve a mean IoU of 0.86, underlining the potential of deep-learning-based CSC segmentation relying entirely on synthetic training data

A Tool to Enable Intraoperative Insertion Force Measurements for Cochlear Implant Surgery

Objective: Residual hearing preservation during cochlear implant (CI) surgery is closely linked to the magnitude of intracochlear forces acting during the insertion process. So far, these forces have only been measured in vitro. Therefore, the range of insertion forces and the magnitude of damage-inducing thresholds in the human cochlea in vivo remain unknown. We aimed to develop a method to intraoperatively measure insertion forces without negatively affecting the established surgical workflow. Initial experiments showed that this requires the compensation of orientation-dependent gravitational forces. Methods: We devised design requirements for a force-sensing manual insertion tool. Experienced CI surgeons evaluated the proposed design for surgical safety and handling quality. Measured forces from automated and manual insertions into an artificial cochlea model were evaluated against data from a static external force sensor representing the gold standard. Results: The finalized manual insertion tool uses an embedded force sensor and inertial measurement unit to measure insertion forces. The evaluation of the proposed design shows the feasibility of orientation-independent insertion force measurements. Recorded forces correspond well to externally recorded reference forces after reliable removal of gravitational disturbances. CI surgeons successfully used the tool to insert electrode arrays into human cadaver cochleae. Conclusion: The presented positive evaluation poses the first step towards intraoperative use of the proposed tool. Further in vitro experiments with human specimens will ensure reliable in vivo measurements. Significance: Intraoperative insertion force measurements enabled by this tool will provide insights on the relationship between forces and hearing outcomes in cochlear implant surgery

Optimization of window settings for coronary arteries assessment using spectral CT-derived virtual monoenergetic imaging

Purpose: To determine the optimal window setting for virtual monoenergetic images (VMI) reconstructed from dual-layer spectral coronary computed tomography angiography (DE-CCTA) datasets. Material and methods: 50 patients (30 males; mean age 61.1 ± 12.4 years who underwent DE-CCTA from May 2021 to June 2022 for suspected coronary artery disease, were retrospectively included. Image quality assessment was performed on conventional images and VMI reconstructions at 70 and 40 keV. Objective image quality was assessed using contrast-to-noise ratio (CNR). Two independent observers manually identified the best window settings (B-W/L) for VMI 70 and VMI 40 visualization. B-W/L were then normalized with aortic attenuation using linear regression analysis to obtain the optimized W/L (O-W/L) settings. Additionally, subjective image quality was evaluated using a 5-point Likert scale, and vessel diameters were measured to examine any potential impact of different W/L settings. Results: VMI 40 demonstrated higher CNR values compared to conventional and VMI 70. B-W/L settings identified were 1180/280 HU for VMI 70 and 3290/900 HU for VMI 40. Subsequent linear regression analysis yielded O-W/L settings of 1155/270 HU for VMI 70 and 3230/880 HU for VMI 40. VMI 40 O-W/L received the highest scores for each parameter compared to conventional (all p &lt; 0.0027). Using O-W/L settings for VMI 70 and VMI 40 did not result in significant differences in vessel measurements compared to conventional images. Conclusion: Optimization of VMI requires adjustments in W/L settings. Our results recommend W/L settings of 1155/270 HU for VMI 70 and 3230/880 HU for VMI 40.</p

Calcineurin Controls Voltage-Dependent-Inactivation (VDI) of the Normal and Timothy Cardiac Channels

Ca2+-entry in the heart is tightly controlled by Cav1.2 inactivation, which involves Ca2+-dependent inactivation (CDI) and voltage-dependent inactivation (VDI) components. Timothy syndrome, a subtype-form of congenital long-QT syndrome, results from a nearly complete elimination of VDI by the G406R mutation in the α11.2 subunit of Cav1.2. Here, we show that a single (A1929P) or a double mutation (H1926A-H1927A) within the CaN-binding site at the human C-terminal tail of α11.2, accelerate the inactivation rate and enhances VDI of both wt and Timothy channels. These results identify the CaN-binding site as the long-sought VDI-regulatory motif of the cardiac channel. The substantial increase in VDI and the accelerated inactivation caused by the selective inhibitors of CaN, cyclosporine A and FK-506, which act at the same CaN-binding site, further support this conclusion. A reversal of enhanced-sympathetic tone by VDI-enhancing CaN inhibitors could be beneficial for improving Timothy syndrome complications such as long-QT and autism

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie