Biomedical Engineering

Biomedical engineering is currently relatively wide scientific area which has been constantly bringing innovations with an objective to support and improve all areas of medicine such as therapy, diagnostics and rehabilitation. It holds a strong position also in natural and biological sciences. In the terms of application, biomedical engineering is present at almost all technical universities where some of them are targeted for the research and development in this area. The presented book brings chosen outputs and results of research and development tasks, often supported by important world or European framework programs or grant agencies. The knowledge and findings from the area of biomaterials, bioelectronics, bioinformatics, biomedical devices and tools or computer support in the processes of diagnostics and therapy are defined in a way that they bring both basic information to a reader and also specific outputs with a possible further use in research and development

NIR-emissive Alkynylplatinum(II) Terpyridyl Complex as a turn-on selective probe for heparin quantification by induced helical self-assembly behaviour

The extent of self-assembly viametal–metal and π-π stacking interactions, induced by the polyanionic biopolymers, enables the class of alkynylplatinum(II) terpyridyl complexes to be applicable for the sensing of important biomacromolecules through the monitoring of spectral changes. Strong demand arises for the design of selective and practical detection techniques for the quantification of heparin, a highly negative-charged polysaccharidethat can function as anticoagulant, due to the prevention of hemorrhagic complications upon overdose usage.Aconvenient sensing protocol for the detection of UFH and LMWH, two common forms of heparins in clinical use, in buffer and biological medium has been demonstrated with the spectral changes associated with the induced self-assembly of a NIR-emissive platinum(II) complex. The detection range has been demonstrated to cover clinical dosage levels and the structurally similar analogues can be effectively differentiated based on their anionic charge density and the formation of supramolecular helical assembly of the platinum(II) complex with them ...postprin

Present and Future of Surface-Enhanced Raman Scattering.

The discovery of the enhancement of Raman scattering by molecules adsorbed on nanostructured metal surfaces is a landmark in the history of spectroscopic and analytical techniques. Significant experimental and theoretical effort has been directed toward understanding the surface-enhanced Raman scattering (SERS) effect and demonstrating its potential in various types of ultrasensitive sensing applications in a wide variety of fields. In the 45 years since its discovery, SERS has blossomed into a rich area of research and technology, but additional efforts are still needed before it can be routinely used analytically and in commercial products. In this Review, prominent authors from around the world joined together to summarize the state of the art in understanding and using SERS and to predict what can be expected in the near future in terms of research, applications, and technological development. This Review is dedicated to SERS pioneer and our coauthor, the late Prof. Richard Van Duyne, whom we lost during the preparation of this article

Pushing the physical limits of infrared chemical imaging: intravascular photoacoustic & mid-infrared photothermal

Providing molecular fingerprint information, vibrational spectroscopy is a powerful tool for chemical analysis. In the mid-infrared window, FT-IR spectroscopy and microscopy have been routinely used for sample characterization. In the near-IR window, near-infrared spectroscopy has been widely used for tissue analysis and for the detection of lipids in the arterial walls. Yet, these traditional linear spectroscopies have intrinsic limitations. FT-IR spectroscopy suffers from a poor spatial resolution and strong water absorption for the study of living systems. Near-infrared spectroscopy avoids water absorption, yet it suffers from a poor, millimeter-scale spatial resolution in tissue analysis. My thesis focuses on breaking these limitations through photoacoustic and photothermal detection approaches. The first part of my thesis is on improving the spatial resolution in catheter-based intravascular photoacoustic (IVPA) imaging. By near-infrared excitation of lipids and acoustic detection, IVPA allows depth-resolved identification of lipid-laden atherosclerotic plaque. Thus far, most IVPA endoscopes use multimode fibers, which do not allow tight focusing of photons. Recent experiments on pulse propagation in multimode graded-index fibers have shown a nonlinear improvement in beam quality. Here, we harness this nonlinear phenomenon for the fiber-delivery of nanosecond laser pulses. We built a photoacoustic catheter 1.4 mm outer diameter, offering a lateral resolution as fine as 30 μm within a depth range of 2.5 mm. Such resolution is one order of magnitude better than current multi-mode fiber-based intravascular photoacoustic catheters. At the same time, the delivered pulse energy can reach as high as 20 μJ, which is two orders of magnitude higher than that of an optical resolution photoacoustic endoscope built with single-mode fiber. These improvements are expected to promote the biomedical application of photoacoustic endoscopes which require both high resolution and high pulse energy. Based on the technical advances, my thesis work further demonstrated longitudinal imaging of the same plaque in the same living animal. Recently developed mid-infrared photothermal (MIP) microscopy overcomes the limitations in FT-IR microscopy by probing the IR absorption-induced photothermal effect using visible light. MIP microscopy yields sub-micrometer spatial resolution with high spectral fidelity and much-reduced water background. The second part of my thesis work pushes the physical limits of MIP microscopy in aspects of detection sensitivity and imaging speed using two approaches. First, taking advantage of the interference scattering effect, the scattering signal from the sample can be greatly enhanced. Together with the relatively large infrared absorption coefficient, the sensitivity of the infrared spectrum is greatly improved, and single virus detection is achieved. Second, by using fluorescence as a thermo-sensitive probe, the temperature raise by infrared absorption can be retrieved in a more efficient way and much higher imaging speed and sensitivity are thus accomplished

Silicon nanowire field-effect transistors for the detection of proteins

In this dissertation I present results on our efforts to increase the sensitivity and selectivity of silicon nanowire ion-sensitive field-effect transistors for the detection of biomarkers, as well as a novel method for wireless power transfer based on metamaterial rectennas for their potential use as implantable sensors. The sensing scheme is based on changes in the conductance of the semiconducting nanowires upon binding of charged entities to the surface, which induces a field-effect. Monitoring the differential conductance thus provides information of the selective binding of biological molecules of interest to previously covalently linked counterparts on the nanowire surface. In order to improve on the performance of the nanowire sensing, we devised and fabricated a nanowire Wheatstone bridge, which allows canceling out of signal drift due to thermal fluctuations and dynamics of fluid flow. We showed that balancing the bridge significantly improves the signal-to-noise ratio. Further, we demonstrated the sensing of novel melanoma biomarker TROY at clinically relevant concentrations and distinguished it from nonspecific binding by comparing the reaction kinetics. For increased sensitivity, an amplification method was employed using an enzyme which catalyzes a signal-generating reaction by changing the redox potential of a redox pair. In addition, we investigated the electric double layer, which forms around charges in an electrolytic solution. It causes electrostatic screening of the proteins of interest, which puts a fundamental limitation on the biomarker detection in solutions with high salt concentrations, such as blood. We solved the coupled Nernst-Planck and Poisson equations for the electrolyte under influence of an oscillating electric field and discovered oscillations of the counterion concentration at a characteristic frequency. In addition to exploring different methods for improved sensing capabilities, we studied an innovative method to supply power to implantable biosensors wirelessly, eliminating the need for batteries. A metamaterial split ring resonator is integrated with a rectifying circuit for efficient conversion of microwave radiation to direct electrical power. We studied the near-field behavior of this rectenna with respect to distance, polarization, power, and frequency. Using a 100 mW microwave power source, we demonstrated operating a simple silicon nanowire pH sensor with light indicator

Amphiphilic Anionic Pt(II) Complexes: from spectroscopic to morphological changes

A new class of amphiphilic anionic platinum(II) bzimpy complexes has been demonstrated to show aggregation in water through PtfflfflfflPt and π–π stacking interactions. An interesting aggregation–partial deaggregation–aggregation process and a morphological transformation from vesicles to nanofibers have been demonstrated. These changes can be systematically controlled by the variation of solvent composition and could readily be probed by UV-vis absorption, emission, NMR, transmission electron microscopy and even with our naked eyes ...postprin

Induced self-assembly and Förster Resonance Energy Transfer Studies of Alkynylplatinum(II) Terpyridine Complex through interaction with water-soluble Poly(phenylene ethynylene sulfonate) and the proof-of-principle demonstration of this two-component ensemble for selective label-free detection of Human Serum Albumin (HSA)

The interaction of conjugated polyelectrolyte, PPE-SO3−, with platinum(II) complexes, [Pt(tpy)(C≡CC6H4CH2NMe3-4)](OTf)2 (1) and [Pt(tpy)(C≡C–CH2NMe3)](OTf)2 (2), has been studied by UV–vis, and steady-state and time-resolved emission spectroscopy. A unique FRET from PPE-SO3−to the aggregated complex 1on the polymer chain with PtfflfflfflPt interactionhas been demonstrated, resulting in the growth of triplet metal-metal-to-ligand charge transfer (3MMLCT) emission ...postprin

New developments in Stimulated Raman Scattering and applications to plastic particle detection in the environment and human tissue

This thesis deals with an advanced laser-based microscopy technique to detect micrometer-size objects with molecular specificity. Applications are shown from the aquatic environment and from the medical world. The final chapters describe an option to increase the penetration depth through scattering samples and simulation software to help optimize the measurement settings. One of the most prominent materials in modern life is plastic, but this also results in the large-scale production of plastic waste. A portion of this waste reaches the environment and is fragmented into small pieces, called microplastics. Microplastics pollution affects the environment and potentially our health in ways we are only beginning to understand. To study it, we need to have a solid measurement and monitoring platform, based on reliable microplastics detection. Detection of microplastics is difficult due to their small size and heterogeneity and they can be found in different types of matrices in the environment and even in the human body. A label-free microscopy imaging technique, called Stimulated Raman Scattering (SRS) microscopy, is able to create images of small particles, like microplastics, based on their molecular structure. SRS makes use of two synchronized pulsed lasers of different colors, of which the energy difference matches a specific vibration of the target molecule. In this thesis, we used SRS for identifying five polymer types. First, we tested the approach on an artificial mixture of plastic particles, and we identified polyethylene terephthalate particles extracted from nail polish, demonstrating also the thousand‐fold higher speed of mapping compared with conventional Raman. Furthermore, we found 12,000 plastic particles per kilogram dry weight in a Rhine estuary sediment sample. SRS was the fastest microplastics detection method at the time of publication. We concluded that SRS can be an efficient method for monitoring microplastics in the environment and potentially many other matrices of interest. Another application area that was studied with SRS is breast tissue from explanted breast implants. Implant failure occurs in approximately a tenth of patients within 10 years, and even without a major rupture silicone can still leak. We showed how SRS can detect silicone material in breast tissue slices, without additional sample treatment. SRS images revealed the distribution and quantity of silicone material. Twenty-two donor-matched capsules from eleven patients experiencing unilateral capsular contraction complaints were included in a clinical study after bilateral explantation surgery. This method showed the correlation between silicone presence and capsular contraction. Depth penetration of the light into the sample is an issue with any light based technique. We showed the use of a long wavelength SRS microscope system capable of greater depth imaging compared with the more common configuration with shorter wavelengths. It showed an improved depth penetration in polyethylene plastic material, in a silicone test sample with embedded polyethylene microbeads, and into subcutaneous fat tissue. In SRS imaging we have to consider multiple parameters that influence the imaging speed, image quality and the spatial resolution. In order to find the optimized imaging setup, we developed two simulation programs for SRS imaging systems with lock-in amplifier. One simulation program was used to find parameters optimized for either image quality or acquisition time. With the second program we evaluated SRS imaging; the simulations agreed very well with experimental SRS images. The same software was used to simulate multiplexed SRS imaging. of six channels, including the inter-channel crosstalk. These programs will be useful for operating an SRS imaging setup, as well as for designing novel setups

Influence of drug/lipid interaction on the entrapment efficiency of isoniazid in liposomes for antitubercular therapy: a multi-faced investigation

Hypothesis. Isoniazid is one of the primary drugs used in tuberculosis treatment. Isoniazid encapsulation in liposomal vesicles can improve drug therapeutic index and minimize toxic and side effects. In this work, we consider mixtures of hydrogenated soy phosphatidylcholine/phosphatidylglycerol (HSPC/DPPG) to get novel biocompatible liposomes for isoniazid pulmonary delivery. Our goal is to understand if the entrapped drug affects bilayer structure. Experiments. HSPC-DPPG unilamellar liposomes are prepared and characterized by dynamic light scattering, $\zeta$-potential, fluorescence anisotropy and Transmission Electron Microscopy. Isoniazid encapsulation is determined by UV and Laser Transmission Spectroscopy. Calorimetry, light scattering and Surface Pressure measurements are used to get insight on adsorption and thermodynamic properties of lipid bilayers in the presence of the drug. Findings. We find that INH-lipid interaction can increase the entrapment capability of the carrier due to isoniazid adsorption. The preferential INH-HSPC dipole-dipole interaction promotes modification of lipid packing and ordering and favors the condensation of a HSPC-richer phase in molar excess of DPPG. Our findings highlight the importance of fundamental investigations of drug-lipid interactions for the optimal design of liposomal nanocarriers.Comment: 28 pages (main manuscript + supplementary information

Application of quantum magnetometers to security and defence screening

Over recent years the sensitivity of alkali-metal vapour magnetometers has been demonstrated to surpass that of even Superconducting Quantum Interference Devices (SQUIDs), the current commercial gold standard in laboratory weak- field magnetometry sensing. Here we present a proof-of-principle approach to building an RF atomic magnetometer which is robust, portable, tunable, non-invasive and operable at room temperature in an unshielded environment. In view of these characteristics, we discuss the potential application of alkali-metal magnetometry in imaging concealed objects, non-destructive evaluation of the structural integrity of metallic objects (e.g. pipelines and aircraft), and detection of rotating motors. We present a cost-effective approach to operating an atomic magnetometer in a Magnetic Induction Tomography (MIT) modality, to non-invasively map the conductivity of conductive objects concealed by conductive materials remotely and in real time. This is achieved by measuring the secondary eld in the subject due to eddy currents circulating as a result of application of a tunable radio-frequency oscillating eld, which overcomes the bandwidth and sensitivity limitations of using coils for sensing as in conventional MIT. In addition, we demonstrate the use of the atomic magnetometer for the remote detection of DC and AC electric motors with an improved response compared with a commercial fluxgate magnetometer in the sub 50 Hz regime (particularly detection down to 15 Hz). Its capability for non-invasive measurement through concrete walls is established, with potential for use in industrial monitoring and detection of illicit activity. Finally, the possibility of detection of submerged targets or for the atomic magnetometer to be mounted on submarine vehicles was explored. Promising results were obtained, but further investigation is required in this environment to establish this as a viable marine detector