Control theory underpins the stabilization of dynamic systems, including cardiac tissue, where disruptions in electrical conduction cause arrhythmias. Current treatments either act rapidly but without precision or deliver targeted interventions that cannot adapt in real time. We present an integrated platform combining optical voltage mapping (OVM), machine learning (ML), and optogenetics for autonomous, real-time detection and correction of cardiac rhythm disorders in vitro. OVM provides high-resolution membrane potential visualization; the ML module identifies arrhythmic events and drives microLED-based light patterns restoring normal conduction; and optogenetics enables light-based modulation of excitable cells. This integration of electrical, optical, and bioelectrical domains through a unified computational control layer enables adaptive, closed-loop rhythm stabilization, a significant advance in real-time electrophysiological interventions. Because inference and actuation run in real time on modest hardware, the same control loop could be embedded into miniaturized devices or microcontrollers, accelerating the transition from in-vitro to in-vivo automated rhythm management.

In this study, we combined finite element method (FEM) based on Ansys and Noesis Optimus software to investigate the effect of bump structures and loading conditions on the electromigration properties of solder bumps in WLCSP. A numerical model considering current density, vacancy concentration, stress and temperature was utilized to calculate the vacancy concentration in solder bumps. The Optimus is an optimization software which can be used to perform the design of experiment (DOE) and sensitivity analysis. To optimize the bump structure, the DOE and response surface modeling (RSM) analysis were performed by using Noesis Optimus. The design optimization based on Noesis Optimus has three main advantages. First, the sensitivity analysis based on DOE results helps to find the most contributing factors. Second, it saves huge time because hundreds of experiments can be executed automatically. Third, it is able to perform evolutionary design optimization directly on RSM to identify the design’s optimal performance point. The maximum and concentration around solder were selected as the index to evaluate the effect of parameter combination on electromigration properties.

This study explores the application of a novel transfer-free method for the synthesis of multilayer Chemical Vapour Deposition (CVD) graphene directly on transparent sub-strates, specifically to create transparent Microelectrode Arrays (MEAs) for optogenetic studies. Traditional methods typically involve a graphene transfer step that can compromise the material's integrity and electrical properties. By eliminating this step, our approach simplifies the fabrication process. The developed MEAs were characterised by Raman spectroscopy, op-tical transmittance, and electrochemical impedance spectroscopy. We also assessed the stability and recording capabilities of the fabricated MEAs, alongside a comparative assessment with a commercial MEA. Turbostratic graphene grown directly on quartz and sapphire was successfully achieved. Our transfer-free MEAs exhibit promising signal detection capabilities, despite a relatively high baseline noise of ∼ 23μ V. and a significantly large impedance at 1 kHz (3.2 to 9.89 M Ω) surpassing values in other studies. The devices exhibited low stability after exposure to liquid media during the soaking and ageing tests, causing large variations in the electrochemical measurements post-exposure. This was due to the permeability of the encapsulation layer and the biodegradability of the molybdenum structures, which led to significant structural and chemical changes in the devices. While further work is required to prevent the failure mechanisms of the device, this study demonstrates the feasibility of transparent MEA fabrication by means of a transfer-free approach directly on quartz substrates.

This dissertation explores the development and application of an interactive optoelectronics platform designed for the precise manipulation of heart rhythm using mini/micro LEDs, primarily within the context of optogenetic applications. The research uses advancements in LED technology for biomedical engineering, focusing on the design, fabrication, and characterization of LED matrix systems. Key objectives include the development of a 48x32
mini LED matrix system, characterized for its electrical, optical, and thermal properties, and evaluated for both interactive and scripted operations. Additionally, the thesis investigates the use of this matrix for optogenetic control of cardiac activities, including optical pacing, conduction block, and the induction and termination of arrhythmias, demonstrating the system’s capability to manipulate cardiomyocytes in vitro. Furthermore, a real-time interactive optoelectronic manipulation system is developed, featuring software for real-time
control and manipulation of optical patterns, incorporating fastmanipulation frame streaming, image processing, and customized calculations. The research also extends to designing an LED matrix of human atrial surface area and the associated driver for potential clinical applications. The conclusions underscore the feasibility and effectiveness of using LED-based optoelectronic systems for precise biological control, laying the groundwork for future biomedical research and clinical therapies, and highlighting the significance of
interdisciplinary approaches in advancing medical technologies.

The heart produces bioelectrical signals, which can be measured as an electrocardiogram (ECG) for the detection of rhythm disturbances. Rapid and precise detection of these arrhythmias is crucial for their termination by closed-looped therapeutic interventions to counteract detrimental effects. However, there is a current lack of such systems tailored for experimental cardiovascular applications. This hampers not only in-depth mechanistic studies but also translational testing of new therapeutic strategies, especially in an untethered manner in awake animal models. To break new ground, recent advances to develop a non-invasive AI-supported heart rhythm monitoring system for untethered automated arrhythmia detection in a continuous manner is combined. This system is housed in a lightweight jacket for mobile use and includes an on-skin ECG sensor, a low-power microprocessor unit, a massive data storage unit, and a power-management system. By implementing a novel hybrid algorithm based on so-called heart rate (R-R) variability and a case-specific AI model, 100% sensitivity and 95% specificity is achieved in detecting atrial arrhythmias within 2 s upon initiation in adult rats. Thereby, the novel system sets the stage for advanced mechanistic studies and therapeutic testing, including closed-loop applications aiming for the termination of a broad range of atrial arrhythmias.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, progressive in nature, and known to have a negative impact on mortality, morbidity, and quality of life. Patients requiring acute termination of AF to restore sinus rhythm are subjected to electrical cardioversion, which requires sedation and therefore hospitalization due to pain resulting from the electrical shocks. However, considering the progressive nature of AF and its detrimental effects, there is a clear need for acute out-of-hospital (i.e., ambulatory) cardioversion of AF. In the search for shock-free cardioversion methods to realize such ambulatory therapy, a method referred to as optogenetics has been put forward. Optogenetics enables optical control over the electrical activity of cardiomyocytes by targeted expression of light-activated ion channels or pumps and may therefore serve as a means for cardioversion. First proof-of-principle for such light-induced cardioversion came from in vitro studies, proving optogenetic AF termination to be very effective. Later, these results were confirmed in various rodent models of AF using different transgenes, illumination methods, and protocols, whereas computational studies in the human heart provided additional translational insight. Based on these results and fueled by recent advances in molecular biology, gene therapy, and optoelectronic engineering, a basis is now being formed to explore clinical translations of optoelectronic control of cardiac rhythm. In this review, we discuss the current literature regarding optogenetic cardioversion of AF to restore normal rhythm in a shock-free manner. Moreover, key translational steps will be discussed, both from a biological and technological point of view, to outline a path toward realizing acute shock-free ambulatory termination of AF.

Background: Optogenetics could offer a solution to the current lack of an ambulatory method for the rapid automated cardioversion of atrial fibrillation (AF), but key translational aspects remain to be studied. Objective: To investigate whether optogenetic cardioversion of AF is effective in the aged heart and whether sufficient light penetrates the human atrial wall. Methods: Atria of adult and aged rats were optogenetically modified to express light-gated ion channels (i.e., red-activatable channelrhodopsin), followed by AF induction and atrial illumination to determine the effectivity of optogenetic cardioversion. The irradiance level was determined by light transmittance measurements on human atrial tissue. Results: AF could be effectively terminated in the remodeled atria of aged rats (97%, n = 6). Subsequently, ex vivo experiments using human atrial auricles demonstrated that 565-nm light pulses at an intensity of 25 mW/mm² achieved the complete penetration of the atrial wall. Applying such irradiation onto the chest of adult rats resulted in transthoracic atrial illumination as evidenced by the optogenetic cardioversion of AF (90%, n = 4). Conclusion: Transthoracic optogenetic cardioversion of AF is effective in the aged rat heart using irradiation levels compatible with human atrial transmural light penetration.

To unlock new research possibilities by acquiring control of action potential (AP) morphologies in excitable cells, we developed an opto-electronic feedback loop-based system integrating cellular electrophysiology, real-time computing, and optogenetic approaches and applied it to monolayers of heart muscle cells. This allowed accurate restoration and preservation of cardiac AP morphologies in the presence of electrical perturbations of different origin in an unsupervised, self-regulatory manner, without any prior knowledge of the disturbance. Moreover, arbitrary AP waveforms could be enforced onto these cells. Collectively, these results set the stage for the refinement and application of opto-electronic control systems to enable in-depth investigation into the regulatory role of membrane potential in health and disease.