Optical fiber-based sensing method for nanoparticle detection through supervised back-scattering analysis: A potential contributor for biomedicine

Background: In view of the growing importance of nanotechnologies, the detection/identification of nanoparticles type has been considered of utmost importance. Although the characterization of synthetic/organic nanoparticles is currently considered a priority (eg, drug delivery devices, nanotextiles, theranostic nanoparticles), there are many examples of “naturally” generated nanostructures - for example, extracellular vesicles (EVs), lipoproteins, and virus - that provide useful information about human physiology or clinical conditions. For example, the detection of tumor-related exosomes, a specific type of EVs, in circulating fluids has been contributing to the diagnosis of cancer in an early stage. However, scientists have struggled to find a simple, fast, and low-cost method to accurately detect/identify these nanoparticles, since the majority of them have diameters between 100 and 150 nm, thus being far below the diffraction limit. Methods: This study investigated if, by projecting the information provided from short-term portions of the back-scattered laser light signal collected by a polymeric lensed optical fiber tip dipped into a solution of synthetic nanoparticles into a lower features dimensional space, a discriminant function is able to correctly detect the presence of 100 nm synthetic nanoparticles in distilled water, in different concentration values. Results and discussion: This technique ensured an optimal performance (100% accuracy) in detecting nanoparticles for a concentration above or equal to 3.89 µg/mL (8.74E+10 particles/mL), and a performance of 90% for concentrations below this value and higher than 1.22E-03 µg/mL (2.74E+07 particles/mL), values that are compatible with human plasmatic levels of tumorderived and other types of EVs, as well as lipoproteins currently used as potential biomarkers of cardiovascular diseases. Conclusion: The proposed technique is able to detect synthetic nanoparticles whose dimensions are similar to EVs and other “clinically” relevant nanostructures, and in concentrations equivalent to the majority of cell-derived, platelet-derived EVs and lipoproteins physiological levels. This study can, therefore, provide valuable insights towards the future development of a device for EVs and other biological nanoparticles detection with innovative characteristics.This work was partly developed under the project NanoSTIMA, funded by the North Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, and through the European Regional Development Fund (ERDF). It was also funded by the Portuguese Foundation for Science and Technology (PhD research grant PD/BD/135023/2017). Rita SR Ribeiro is currently working at 4Dcell and Elvesys, Paris, France

Surface Plasmon Resonance Sensitivity Enhancement Based on Protonated Polyaniline Films Doped by Aluminum Nitrate

Complex composite films based on polyaniline (PANI) doped hydrochloric acid (HCl) incorporated with aluminum nitrate (Al(NO3)3) on Au-layer were designed and synthesized as a surface plasmon resonance (SPR) sensing device. The physicochemical properties of (PANI-HCl)/Al(NO3)3 complex composite films were studied for various Al(NO3)3 concentrations (0, 2, 4, 8, 16, and 32 wt.%). The refractive index of the (PANI-HCl)/Al(NO3)3 complex composite films increased continuously as Al(NO3)3 concentrations increased. The electrical conductivity values increased from 5.10 µS/cm to 10.00 µS/cm as Al(NO3)3 concentration increased to 32 wt.%. The sensitivity of the SPR sensing device was investigated using a theoretical approach and experimental measurements. The theoretical system of SPR measurement confirmed that increasing Al(NO3)3 in (PANI-HCl)/Al(NO3)3 complex composite films enhanced the sensitivity from about 114.5 [Deg/RIU] for Au-layer to 159.0 [Deg/RIU] for Au-((PANI-HCl)/Al(NO3)3 (32 wt.%)). In addition, the signal-to-noise ratio for Au-layer was 3.95, which increased after coating by (PANI-HCl)/Al(NO3)3 (32 wt.%) complex composite layer to 8.82. Finally, we conclude that coating Au-layer by (PANI-HCl)/Al(NO3)3 complex composite films enhances the sensitivity of the SPR sensing device

Efficient implementation of resource-constrained cyber-physical systems using multi-core parallelism

The quest for more performance of applications and systems became more challenging in the recent years. Especially in the cyber-physical and mobile domain, the performance requirements increased significantly. Applications, previously found in the high-performance domain, emerge in the area of resource-constrained domain. Modern heterogeneous high-performance MPSoCs provide a solid foundation to satisfy the high demand. Such systems combine general processors with specialized accelerators ranging from GPUs to machine learning chips. On the other side of the performance spectrum, the demand for small energy efficient systems exposed by modern IoT applications increased vastly. Developing efficient software for such resource-constrained multi-core systems is an error-prone, time-consuming and challenging task. This thesis provides with PA4RES a holistic semiautomatic approach to parallelize and implement applications for such platforms efficiently. Our solution supports the developer to find good trade-offs to tackle the requirements exposed by modern applications and systems. With PICO, we propose a comprehensive approach to express parallelism in sequential applications. PICO detects data dependencies and implements required synchronization automatically. Using a genetic algorithm, PICO optimizes the data synchronization. The evolutionary algorithm considers channel capacity, memory mapping, channel merging and flexibility offered by the channel implementation with respect to execution time, energy consumption and memory footprint. PICO's communication optimization phase was able to generate a speedup almost 2 or an energy improvement of 30% for certain benchmarks. The PAMONO sensor approach enables a fast detection of biological viruses using optical methods. With a sophisticated virus detection software, a real-time virus detection running on stationary computers was achieved. Within this thesis, we were able to derive a soft real-time capable virus detection running on a high-performance embedded system, commonly found in today's smart phones. This was accomplished with smart DSE algorithm which optimizes for execution time, energy consumption and detection quality. Compared to a baseline implementation, our solution achieved a speedup of 4.1 and 87\% energy savings and satisfied the soft real-time requirements. Accepting a degradation of the detection quality, which still is usable in medical context, led to a speedup of 11.1. This work provides the fundamentals for a truly mobile real-time virus detection solution. The growing demand for processing power can no longer satisfied following well-known approaches like higher frequencies. These so-called performance walls expose a serious challenge for the growing performance demand. Approximate computing is a promising approach to overcome or at least shift the performance walls by accepting a degradation in the output quality to gain improvements in other objectives. Especially for a safe integration of approximation into existing application or during the development of new approximation techniques, a method to assess the impact on the output quality is essential. With QCAPES, we provide a multi-metric assessment framework to analyze the impact of approximation. Furthermore, QCAPES provides useful insights on the impact of approximation on execution time and energy consumption. With ApproxPICO we propose an extension to PICO to consider approximate computing during the parallelization of sequential applications

Application of the PAMONO-sensor for quantification of microvesicles and determination of nano-particle size distribution

The PAMONO-sensor (plasmon assisted microscopy of nano-objects) demonstrated an ability to detect and quantify individual viruses and virus-like particles. However, another group of biological vesicles—microvesicles (100–1000 nm)—also attracts growing interest as biomarkers of different pathologies and needs development of novel techniques for characterization. This work shows the applicability of a PAMONO-sensor for selective detection of microvesicles in aquatic samples. The sensor permits comparison of relative concentrations of microvesicles between samples. We also study a possibility of repeated use of a sensor chip after elution of the microvesicle capturing layer. Moreover, we improve the detection features of the PAMONO-sensor. The detection process utilizes novel machine learning techniques on the sensor image data to estimate particle size distributions of nano-particles in polydisperse samples. Altogether, our findings expand analytical features and the application field of the PAMONO-sensor. They can also serve for a maturation of diagnostic tools based on the PAMONO-sensor platform