Background: The diaphragm is poorly monitored in the Intensive care unit (ICU), despite its evident importance in respiration. Ultrasound (US) is frequently employed to evaluate diaphragm thickness (DT) and diaphragm thickening factor (DTF) but requires expertise and only covers a small diaphragm area. Therefore, advanced US (post-)processing techniques are being investigated for diaphragm applications, including speckle tracking methods.
Objective: The primary aim of this pilot study was to develop an algorithm enabling DT quantification. Second, both an existing Fourier-based (FBST) and intensity-based speckle tracking (IBST) algorithm were modified to determine their feasibility in diaphragm strain quantification.
Results: Minimal (DTmin, mm) and maximal DT (DTmax, mm), and DTF (%) values were 1.9 ± 0.4, 2.3 ± 0.5, and 22.6 ± 10.9 in the MV patient group, and 2.2 ± 0.4, 3.7 ± 1.5 and 66.5 ± 45.0 in the volunteer group (all p > 0.05). Correlation of DT algorithm variables and manual expert grading were allsignificant, with a good correlation in DTmax (ICC 0.9, r or ρ 0.7, p < 0.001) and a moderate correlation in DTmin and DTF (ICC 0.7, r or ρ 0.7, p < 0.001 and p = 0.001, respectively). Inter- and intra-rater reproducibility of manual DT assessment was poor (ICC < 0.4 and r or ρ < 0.2). GLS (%) and GLSR (%/s) values were -32.0 ± 19.8 and -6.6 ± 3.8 in the patient group and -40.3 ± 17.3 and -10.4 ± 6.8 in the volunteer group, respectively (all p > 0.05). IBST scores were 26.2 ± 17.6 in the patient group and 68.1 ± 32.5 in the volunteer group (p = 0.009). IBST score values showed a good correlation with DTF (r or ρ 0.7, p = 0.003), and a moderate, negative correlation with DTmin (r or ρ -0.5, p = 0.043). No significant correlations were seen between the remaining manual expert DT assessment and algorithm-derived FBST and IBST variables.Conclusion: DT quantification using the algorithm developed during this study correlated to conventional US expert assessment. Poor reproducibility of current diaphragm function quantification supports the need for such an automated assessment. The clinical value of diaphragm strain assessment using the modified FBST and IBST algorithms remains unclear. Further research involving a widely defined gold standard technique in diaphragm function quantification is warranted.

The current standard for organ-on-chip substrate materials is polydimethylsiloxane (PDMS). PDMS has many beneficial properties such as biocompatibility, transparency, elasticity, and easy prototyping. The main disadvantages of PDMS are its hydrophobicity (reducing cell attachment and cell proliferation), quick hydrophobic recovery (within a few hours) after surface modification, and unselective absorption of small molecules, altering drug concentration during testing or causing cross-contamination between channels. To overcome these shortcomings, an alternative material lacking the disadvantages and retaining the advantages of PDMS is needed in the field. Ostemer 324, Ostemer 220 and a variation of PDMS (PDMS+) were characterized to determine whether they would be a suitable alternative to PDMS as substrate material. The materials were compared to PDMS and characterized for spin-coating and curing on silicon wafers, moulding, etching, surface wettability before and after surface modification (plasma treatment), stiffness, optical transparency, biocompatibility and absorption of small molecules. The results of this work show that Ostemer 324 appears to be a promising alternative, with similar characteristics to PDMS. The main advantage is its hydrophilic surface, which becomes even more hydrophilic after plasma treatment, and slow hydrophobic recovery rate. However, its curing time is longer, the material is stiffer and not easy to mould. Ostemer 220 shows very poor adhesion on Teflon coated silicon wafers, is hard to mould, and shows inconsistent results during biocompatibility testing. PDMS+ is very similar to PDMS, and improves upon the latter in terms of surface wettability after surface modification, hydrophobic recovery and small molecule absorption.

Background: The prevention of ventilator-induced lung injury (VILI) is an important topic in criticalcare. Lung overdistention is a great attributor to VILI. Regional evaluation of the pulmonary mechanicsis a relatively new method and is currently being studied using electrical impedance tomography (EIT)and computed tomography (CT). However, ultrasonography may be an effective alternative tomeasure lung overdistention by quantifying lung sliding.
Objective: The primary aim of this study was to explore if lung sliding can be quantified using in-housemade speckle tracking algorithms. Second, the usability of lung sliding quantification to detect lungoverdistention was investigated.
Methods: Two speckle tracking algorithms were built and validated to quantify lung sliding. Adultpatients admitted to the ICU were prospectively examined using ultrasound. Ultrasound images wereanalyzed offline using the in-house developed Fourier-Based Speckle Tracking algorithm (FBST) andthe Intensity-Based Speckle Tracking algorithm (IBST). The performance of the best algorithm wasvalidated against the manual evaluation of lung sliding by experts and validated against lungcompliance. Besides, the performance of the best algorithm was investigated by reproducibilitytesting. Finally, we tested the algorithm for its ability to detect lung overdistention.
Results: The FBST algorithm could not reliably quantify lung sliding and was not further evaluated.However, the IBST algorithm showed an overall success rate of 88%. Moreover, the IBST algorithmdifferentiated normal and moderate lung sliding with a mean IBST score of 12.1 and 29, respectively(p<0.001). A positive correlation was measured between IBST score and lung compliance (β 0.15, SE0.025, 95% CI 0.101-0.208, p <0.001). The reproducibility test calculated a relative standard error of2.7. Finally, a difference was found in IBST scores between patients with a PEEP value <12 and ≥12with a mean ± SD of 20.9 ± 7 and 12.6 ± 6, p < 0.05, respectively.
Conclusion: The IBST algorithm enables a robust lung sliding quantification. The IBST scores correlatewell with expert opinion and lung compliance, but the reliability needs improvement. Our results showthat detection of lung overdistention using ultrasound is feasible. Further clinical studies should assessif ultrasonography can measure lung overdistention.

The functioning of the brain depends on the interplay between a large number of neurons. To understand the information processing in neuronal networks, we need tools to record the electrical activity of cells at high resolution. Microelectrode arrays (MEAs) are predominantly used to measure neuronal activity
at high spatial and temporal resolution. With the advent of complementary metal-oxide-semiconductor (CMOS) based MEAs, it has been possible to design high-density MEAs with electrode sizes comparable to that of the individual neurons, allowing sub-cellular resolution. CMOS technology has also facilitated the on-chip signal conditioning needed to record the low-amplitude bio-signals with superior signal quality. In this thesis, a readout architecture for in-vitro MEAs has been proposed for a low-noise extracellular action potential (AP) readout.

One of the challenges in MEA implementation is the design of thousands of low-noise readout channels for simultaneously recording the signals. There is a need to design low-noise ADCs with optimal power and area consumption. In this thesis, a unique low-noise oscillator based sigma-delta ADC has been designed for MEA applications. With the advantages of oversampling and time-encoding techniques, the in-band noise has been optimized, without increased hardware complexity. The simple implementation of this proposed ADC makes it efficient in terms of area and power consumption.

The integrated circuit for this oscillator based sigma-delta ADC has been implemented in 0.18 um CMOS technology to demonstrate the feasibility of high-order oscillator-based ADCs for low-noise extracellular AP readout. It was possible to obtain a noise below 5 uV_RMS (simulations) and power consumption under 3 uW using this ADC, which approximately occupies an area of 0.002 mm². The action potential readout system implemented with this ADC has been taped-out for further analysis through measurements.

Neurostimulators have been developed over the past few decades to treat various diseases, such as Parkinson’s disease, chronic pain, epilepsy, migraine and bladder dysfunction. One of the major design challenges is the selection of a powering method that could supply mW power levels to miniaturized implanted devices. Among several methods, wireless power transfer is often used to directly supply the electronics or to recharge an implanted battery. In particular, the interest in ultrasonic waves as source of power and data for implantable medical devices has recently grown, particularly due to the advantages over RF and inductive coupling power transfer. In fact, ultrasounds can deliver higher power to mm-sized and deeply (> 10 cm) implanted receivers than the other techniques. Moreover, acoustic waves do not interfere with electromagnetic fields.Conventionally, biphasic constant current or constant voltage pulses are selected for stimulating nerve tissue. The first (usually cathodic) phase has the purpose of activating the excitable nerve fibres, while the second (usually anodic) phase reverses the direction of the stimulation current to avoid long-term accumulation of charge. Alternatively, Ultra-High-Frequency stimulation can be employed. This consists of current or voltage pulses at a high frequency (≥ 1 MHz), which are obtained from a DC source and the operation of high-frequency switches. In both techniques, when a wireless supply is chosen, the received AC signal is rectified, stored and regulated to operate the usually low-voltage blocks of the rest of the system. Nonetheless, up-conversion of the signal is often required to provide enough voltage compliance to operate an output stage connected to the stimulating electrodes.Taking a more radical approach, it is possible to avoid the lossy conversion from AC to regulated DC and from that to high-frequency stimulation by eliminating the need of power storage, regulation and up-conversion. To this end, the aim of this work was to design a circuit topology that generates ultra-high-frequency pulses by rectifying the sinusoid obtained from an ultrasound transducer and using the obtained waveform to directly stimulate the tissue in a biphasic fashion. This could result in a highly efficient and miniature circuit, which has the potential to be used for stimulating small peripheral nerves. Simulations in LTSpice were conducted to analyse the performance of the proposed system. The operation was then verified by measurements with a fabricated prototype, which was capable of providing biphasic pulses by receiving a signal from ultrasound piezoelectric transducers and driving a pair of electrodes.