Single-cell isolation is a truly transformative tool for the understanding of biological systems. It allows single-cell molecular analyses and considers the heterogeneity of cell populations, which is of particular relevance for the diagnosis and treatment of evolving diseases and for personalized medicine. Single-cell isolation is also a key process in cell line development, where it is used to obtain stable and high producing clonally-derived cell lines, thus contributing to the efficiency, safety and reproducible quality of the drug produced. High producing clonally-derived cell lines are however rare events and their identification is a time-consuming process that requires the screening of thousands of clones. Therefore, there is an unmet need for a device that would allow the fast and efficient isolation of single cells, while preserving their integrity and providing an insurance of their clonality.We proposed earlier an impedance based pipetting technology for isolation of single cells (Bonzon et al., 2020), with initial validations for state-of-the-art stem cell in-vitro and in-vivo assays (Muller et al., 2020). Here, we present the transition from this pioneering technology developed in an academic setting into an automated instrument, called DispenCell-S1, allowing for traceable isolation of single cells.We developed and validated models predicting the performances for 96-well plates single-cell isolation. This resulted in a time of dispense down to 3 min and a plate filling rate up to 96%. Finally, we obtained an impedance signal reliability for proof of single particle isolation of 99% with beads and ranging from 93 to 95% with CHO cells.

Microsample analysis is highly beneficial in blood-based testing where cutting-edge bioanalytical technologies enable the analysis of volumes down to a few tens of microliters. Despite the availability of analytical methods, the difficulty in obtaining high-quality and standardized microsamples at the point of collection remains a major limitation of the process. Here, we detail and model a blood separation principle which exploits discrete viscosity differences caused by blood particle sedimentation in a laminar flow. Based on this phenomenon, we developed a portable capillary-driven microfluidic device that separates blood microsamples collected from finger-pricks and delivers 2 µL of metered serum for bench-top analysis. Flow cytometric analysis demonstrated the high purity of generated microsamples. Proteomic and metabolomic analyses of the microsamples of 283 proteins and 1351 metabolite features was consistent with samples generated via a conventional centrifugation method. These results were confirmed by a clinical study scrutinising 8 blood markers in obese patients.

Recent advances in remote powering and telemetry permitted the use of sensors inside body. A few studies have been already done on smart knee prostheses, but all focused on monitoring the in-vivo contact forces and moments. A smart design, compatible with mechanical structure of commercially-available knee prostheses, that provides force and accurate kinematics feedback was suggested with all electronics housed in the polyethylene insert (PE). The current work addresses the designed kinematics and force measurement system of that smart implant and its validation in a robotic knee simulator.

Total knee arthroplasty is a widely performed surgical technique. Soft tissue force balancing during the operation relies strongly on the experience of the surgeon in equilibrating tension in the collateral ligaments. Little information on the forces in the implanted prosthesis is available during surgery and post-operative treatment. This paper presents the design, fabrication and testing of an instrumented insert performing force measurements in a knee prosthesis. The insert contains a closed structure composed of printed circuit boards and incorporates a microfabricated polyimide thin-film piezoresistive strain sensor for each condylar compartment. The sensor is tested in a mechanical knee simulator that mimics in-vivo conditions. For characterization purposes, static and dynamic load patterns are applied to the instrumented insert. Results show that the sensors are able to measure forces up to 1.5 times body weight with a sensitivity fitting the requirements for the proposed use. Dynamic testing of the insert shows a good tracking of slow and fast changing forces in the knee prosthesis by the sensors.

In this work we present the implantable and wearable measurement system developed for smart knee prostheses monitoring. The kinematic measurement system contains three anisotropic magnetoresistive sensors embedded into the polyethylene part of the prostheses. The kinematic measurement system also has two inertial measurement units to be worn by the subject on the shank and thigh. Each of this inertial measurement units consisted of a 3D accelerometer and a 3D gyroscope. The force measurement system contains implantable strain gauges that connected in two separate Wheatstone bridges and embedded in a designed capsule-like structure. These systems were validated in a robotic knee simulator against reference force and kinematics systems. The best angle estimator performed with an RMS error of 1.18°±0.25° over four different walking patterns, while the force sensors showed linear behavior in measuring the applied forces, where linear models obtained R 2 s larger than 0.98.

This paper describes the development of a polyimide/SU-8 catheter-tip MEMS gauge pressure sensor. Finite element analysis was used to investigate critical parameters, impacting on the device design and sensing characteristics. The sensing element of the device was fabricated by polyimide-based micromachining on a flexible membrane, using embedded thin-film metallic wires as piezoresistive elements. A chamber containing this flexible membrane was sealed using an adapted SU-8 bonding technique. The device was evaluated experimentally and its overall performance compared with a commercial silicon-based pressure sensor. Furthermore, the device use was demonstrated by measuring blood pressure and heart rate in vivo.