No description available.

In this report, we focus on Biofluids problems, specifically the Stokes Equation. The method of regularized Stokeslets can be derived from bound- ary integral equations derived from the Lorentz reciprocal identity. When body forces are known, this is a direct numerical approximation of an in- tegral, resulting in a summation to determine the fluid velocity. In certain cases, which this report is focused on, we know the velocity and want to determine the forces on a structure immersed in a fluid. This results in a lin- ear system Af = u, where A is a square dense matrix. We study different methods to solve this system of equations to determine the force f on the structure. For solving a linear system with a dense coefficient matrix, the backslash command in MATLAB can be used. This will use an efficient and robust direct method for solving a smaller matrix, but this is not an efficient method for a large, dense coefficient matrix. For a large, dense coefficient ma- trix, we will explore other direct methods as well as several iterative methods to determine computation time and error on a test case with an exact solu- tion. For direct methods, we will study backslash, LU factorization and QR factorization methods. For iterative methods, we stuied Jacobi, Gauss-Seidel, SOR, GMRES, CG, CGS, BICGSTAB and Schulz CG methods for these bioflu- ids applications. All of these methods have different requirements. For our coefficient matrix A, we identified specific properties and then used proper methods, both direct and iterative. Result showed that iterative methods are more efficient then direct method for large size A. Schulz CG was slower but had a smaller error for the test case where there was an exact solution.

No description available.

Microhemodynamics is the study of blood flow in small vessels, usually on the order of 50 to 100 µm. The in vitro study of blood flow in small channels is analogous to the in vivo study of the microcirculation. At this scale the Reynolds and Womersly numbers are significantly less than 1 and the viscous stress and pressure gradient are the main determinant of flow. Blood is a non-homogeneous, non-Newtonian fluid and this complex composition and behavior has a greater impact at the microscale. A key parameter is the shear stress at the wall, which is involved in many processes such as platelet activation, gas exchange, embryogenesis and angiogenesis. In order to measure the shear rate in these blood flows the velocity profile must be measured. The measured profile can be characterized by the maximum velocity, the flow rate, the shear rate at the wall, or a shape parameter reflecting the bluntness of the velocity profile. The technique of micro-particle image velocimetry (µPIV) was investigated to measure the velocity profiles of blood microflows. The material of the channel, the type of tracer particles, the camera used, and the choice in data processing were all validated to improve the overall accuracy of µPIV as a blood microflow measurement method. The knowledge gained through these experiments is of immediate interest to applications such as the design of lab-on-a-chip components for blood analysis, analysis of blood flow behavior, understanding the shear stress on blood in the microcirculation and blood substitute analysis. Polymer channels were fabricated from polydimethylsiloxane (PDMS) by soft lithography in a clean room. PDMS was chosen for ease of fabrication and biocompatibility. The contacting properties of saline, water, and blood with various polymer channel materials was measured. As PDMS is naturally hydrophilic, surface treatment options were explored. Oxygenated plasma treatment was found to be less beneficial for blood than for water. The choice of camera and tracer particles were validated. Generally, for in vivo studies, red blood cells (RBCs) are used as tracer particles for the µPIV method, while for in vitro studies, artificial fluorescent micro particles are added to the blood. It is demonstrated here that the use of RBCs as tracer particles creates a large depth of correlation (DOC), which can approach the size of vessel itself and decreases the accuracy of the method. Next, the accuracy of each method is compared directly. Pulsed images used in conjunction with fluorescing tracer particles are shown to give results closest to theoretical approximations. The effect of the various post-processing methods currently available were compared for accuracy and computation time. It was shown that changing the amount of overlap in the post-processing parameters affects the results by nearly 10%. Using the greatest amount of correlation window overlap with elongated windows aligned with the flow was shown to give the best results when coupled with a image pre-processing method previously published for microflows of water. Finally the developed method was applied to a relevant biomedical engineering problem: the evaluation of blood substitutes and blood viscosity modifiers. Alginate is a frequently used viscosity modifier which has many uses in industry, including biomedical applications. Here the effect of alginate on the blood rheology, i.e., the shape of the velocity profile and the maximum velocity of blood flow in microchannels, was investigated. Alginate was found to blunt the shape of the velocity profile while also decreasing the shear rate at the wall. Overall, the accuracy of µPIV measurements of blood flows has been improved by this thesis. The work presented here has extended the known methods and accuracy issues of blood flow measurements in µPIV, improved the understanding of the blood velocity profile behavior, and applied that knowledge and methods to interesting, relevant problems in biomedical and biofluids engineering.

Microhemodynamics is the study of blood flow in small vessels, usually on the order of 50 to 100 µm. The in vitro study of blood flow in small channels is analogous to the in vivo study of the microcirculation. At this scale the Reynolds and Womersly numbers are significantly less than 1 and the viscous stress and pressure gradient are the main determinant of flow. Blood is a non-homogeneous, non-Newtonian fluid and this complex composition and behavior has a greater impact at the microscale. A key parameter is the shear stress at the wall, which is involved in many processes such as platelet activation, gas exchange, embryogenesis and angiogenesis. In order to measure the shear rate in these blood flows the velocity profile must be measured. The measured profile can be characterized by the maximum velocity, the flow rate, the shear rate at the wall, or a shape parameter reflecting the bluntness of the velocity profile. The technique of micro-particle image velocimetry (µPIV) was investigated to measure the velocity profiles of blood microflows. The material of the channel, the type of tracer particles, the camera used, and the choice in data processing were all validated to improve the overall accuracy of µPIV as a blood microflow measurement method. The knowledge gained through these experiments is of immediate interest to applications such as the design of lab-on-a-chip components for blood analysis, analysis of blood flow behavior, understanding the shear stress on blood in the microcirculation and blood substitute analysis. Polymer channels were fabricated from polydimethylsiloxane (PDMS) by soft lithography in a clean room. PDMS was chosen for ease of fabrication and biocompatibility. The contacting properties of saline, water, and blood with various polymer channel materials was measured. As PDMS is naturally hydrophilic, surface treatment options were explored. Oxygenated plasma treatment was found to be less beneficial for blood than for water. The choice of camera and tracer particles were validated. Generally, for in vivo studies, red blood cells (RBCs) are used as tracer particles for the µPIV method, while for in vitro studies, artificial fluorescent micro particles are added to the blood. It is demonstrated here that the use of RBCs as tracer particles creates a large depth of correlation (DOC), which can approach the size of vessel itself and decreases the accuracy of the method. Next, the accuracy of each method is compared directly. Pulsed images used in conjunction with fluorescing tracer particles are shown to give results closest to theoretical approximations. The effect of the various post-processing methods currently available were compared for accuracy and computation time. It was shown that changing the amount of overlap in the post-processing parameters affects the results by nearly 10%. Using the greatest amount of correlation window overlap with elongated windows aligned with the flow was shown to give the best results when coupled with a image pre-processing method previously published for microflows of water. Finally the developed method was applied to a relevant biomedical engineering problem: the evaluation of blood substitutes and blood viscosity modifiers. Alginate is a frequently used viscosity modifier which has many uses in industry, including biomedical applications. Here the effect of alginate on the blood rheology, i.e., the shape of the velocity profile and the maximum velocity of blood flow in microchannels, was investigated. Alginate was found to blunt the shape of the velocity profile while also decreasing the shear rate at the wall. Overall, the accuracy of µPIV measurements of blood flows has been improved by this thesis. The work presented here has extended the known methods and accuracy issues of blood flow measurements in µPIV, improved the understanding of the blood velocity profile behavior, and applied that knowledge and methods to interesting, relevant problems in biomedical and biofluids engineering.

The increased use of mass spectrometry in the clinical setting has led to a demand for high sample throughput. Developments such as ultra high performance liquid chromatography and the ambient ionization techniques enable high sample throughput by reducing chromatographic run times or by removing the requirement for sample preparation and fractionation prior to analysis. This thesis assesses the reproducibility and robustness of these high throughput techniques for the analysis of clinical and pharmaceutical samples by ion mobility-mass spectrometry. The rapid quantitative analysis of the urinary biomarkers of chronic obstructive pulmonary disease, desmosine and isodesmosine has been performed by ultra high performance liquid chromatography combined with ion mobility-mass spectrometry. The determination of health status based on the free unbound fraction rather than the total bound and unbound desmosine and isodesmosine, significantly reduces the time taken in sample preparation. The potential for direct analysis of the urinary metabolites from undeveloped TLC plates using a solvent extraction surface sample probe is demonstrated. The use of a solvent gradient for the extraction separates urinary metabolites from salts and other matrix components and allows fractionation of the sample as a result of differential retention on the undeveloped RP-TLC plate. This separation, combined with ion mobility-mass spectrometry provides a rapid ambient ionization method for urinary profiling. The combination of a thermal desorption probe with extractive electrospray ionization has been applied to the direct detection of a known genotoxic impurity from a surrogate active pharmaceutical ingredient. The volatility of the impurity compared to the matrix, allowed selective thermal desorption of the analyte, which was ionized by extractive electrospray and detected by mass spectrometry. The use of a rapid on-probe derivatisation reaction, combined with thermal desorption is demonstrated for the direct determination of urinary creatinine. The aqueous acylation of creatinine significantly increases the volatility of the analyte enabling separation from the urine matrix and analysis by thermal desorption extractive electrospray combined with ion mobility-mass spectrometry.

Dreiwertige Actinide (An(III)) und Lanthanide (Ln(III)) stellen im Falle ihrer Inkorporation eine ernste Gefahr für die Gesundheit des Menschen dar. An(III) sind künstlich erzeugte, stark radioaktive Elemente, die insbesondere bei der nuklearen Energiegewinnung in Kernkraftwerken entstehen. Durch Störfälle oder nicht fachgerechte Lagerung radioaktiven Abfalls können sie in die Umwelt und die Nahrungskette des Menschen gelangen. Ln(III) sind hingegen nicht radioaktive Elemente, die natürlicherweise vorkommen und für vielfältige Anwendungen in Technik und Medizin abgebaut werden. Folglich kann der Mensch sowohl mit An(III) als auch Ln(III) in Kontakt kommen bzw. sie inkorporieren. Es ist daher von enormer Wichtigkeit, das Verhalten dieser Elemente im menschlichen Körper aufzuklären. Während makroskopische Vorgänge wie Verteilung, Anreicherung und Ausscheidung bereits sehr gut untersucht sind, ist das Wissen hinsichtlich der chemischen Bindungsform (Speziation) von An(III) und Ln(III) in Körperflüssigkeiten noch sehr lückenhaft. In der vorliegenden Arbeit wurde daher erstmals die chemische Bindungsform von Cm(III) und Eu(III) in natürlichem menschlichem Urin (in vitro) spektroskopisch aufgeklärt und die gebildeten Komplexe identifiziert. Hierzu wurden auch grundlegende Untersuchungen zur Komplexierung von Cm(III) und Eu(III) in synthetischem Modellurin sowie mit den urinrelevanten organischen Modellliganden Harnstoff, Alanin, Phenylalanin, Threonin und Citrat durchgeführt und die noch unbekannten Komplexbildungskonstanten bestimmt. Abschließend wurden alle experimentellen Ergebnisse mit Literaturdaten und Vorherberechnungen mittels thermodynamischer Modellierung verglichen. Auf Grund der hervorragenden Lumineszenzeigenschaften von Cm(III) und Eu(III) konnte insbesondere auch die Eignung der zeitaufgelösten laserinduzierten Fluoreszenzspektroskopie (TRLFS) als Methode zur Untersuchung dieser Metallionen in unbehandelten, komplexen biologischen Flüssigkeiten demonstriert werden. Die Ergebnisse dieser Arbeit liefern damit neue Erkenntnisse zu den biochemischen Reaktionen von An(III) und Ln(III) in Körperflüssigkeiten auf molekularer Ebene und tragen zu einem besseren Verständnis der bekannten, makroskopischen Effekte dieser Elemente bei. Darüber hinaus sind sie die Grundlage weiterführender in-vivo-Untersuchungen.

No description available.

Dreiwertige Actinide (An(III)) und Lanthanide (Ln(III)) stellen im Falle ihrer Inkorporation eine ernste Gefahr für die Gesundheit des Menschen dar. An(III) sind künstlich erzeugte, stark radioaktive Elemente, die insbesondere bei der nuklearen Energiegewinnung in Kernkraftwerken entstehen. Durch Störfälle oder nicht fachgerechte Lagerung radioaktiven Abfalls können sie in die Umwelt und die Nahrungskette des Menschen gelangen. Ln(III) sind hingegen nicht radioaktive Elemente, die natürlicherweise vorkommen und für vielfältige Anwendungen in Technik und Medizin abgebaut werden. Folglich kann der Mensch sowohl mit An(III) als auch Ln(III) in Kontakt kommen bzw. sie inkorporieren. Es ist daher von enormer Wichtigkeit, das Verhalten dieser Elemente im menschlichen Körper aufzuklären. Während makroskopische Vorgänge wie Verteilung, Anreicherung und Ausscheidung bereits sehr gut untersucht sind, ist das Wissen hinsichtlich der chemischen Bindungsform (Speziation) von An(III) und Ln(III) in Körperflüssigkeiten noch sehr lückenhaft. In der vorliegenden Arbeit wurde daher erstmals die chemische Bindungsform von Cm(III) und Eu(III) in natürlichem menschlichem Urin (in vitro) spektroskopisch aufgeklärt und die gebildeten Komplexe identifiziert. Hierzu wurden auch grundlegende Untersuchungen zur Komplexierung von Cm(III) und Eu(III) in synthetischem Modellurin sowie mit den urinrelevanten organischen Modellliganden Harnstoff, Alanin, Phenylalanin, Threonin und Citrat durchgeführt und die noch unbekannten Komplexbildungskonstanten bestimmt. Abschließend wurden alle experimentellen Ergebnisse mit Literaturdaten und Vorherberechnungen mittels thermodynamischer Modellierung verglichen. Auf Grund der hervorragenden Lumineszenzeigenschaften von Cm(III) und Eu(III) konnte insbesondere auch die Eignung der zeitaufgelösten laserinduzierten Fluoreszenzspektroskopie (TRLFS) als Methode zur Untersuchung dieser Metallionen in unbehandelten, komplexen biologischen Flüssigkeiten demonstriert werden. Die Ergebnisse dieser Arbeit liefern damit neue Erkenntnisse zu den biochemischen Reaktionen von An(III) und Ln(III) in Körperflüssigkeiten auf molekularer Ebene und tragen zu einem besseren Verständnis der bekannten, makroskopischen Effekte dieser Elemente bei. Darüber hinaus sind sie die Grundlage weiterführender in-vivo-Untersuchungen.

Είναι πλέον αποδεκτό ότι οι αγγειακές βιολογικές διαδικασίες επηρεάζονται από την τοπική αιμοδυναμική. Πειράματα in vivo, in vitro και αριθμητικές μελέτες επιβεβαίωσαν ότι τα μοντέλα της ροής στην αρτηριοφλεβική αναστόμωση (ΑΦΑ) είναι αυστηρά εξαρτημένα από τη γεωμετρία της περιοχής. Στην παρούσα εργασία μελετήθηκε το πεδίο ροής του αίματος σε "εικονικές γεωμετρίες" των ΑΦΑ μέσω μεθόδων υπολογιστικής ρευστομηχανικής. Με τον όρο "εικονική γεωμετρία" καλούμε μια γεωμετρία που δεν προσδιορίζεται από μετρήσεις σε πραγματικές αναστομώσεις αλλά προσομοιάζει προσεγγιστικά σ'αυτή. Ως οριακές συνθήκες του προβλήματος ετέθησαν κατανομές ταχύτητας που είχαν μετρηθεί σε συγκεκριμένες θέσεις εισόδου στο επίπεδο αρτηρίας και φλέβας της ΑΦΑ. Η μελέτη του πεδίου ροής περιλαμβάνει την κατανομή ταχυτήτων σε όλη την περιοχή της ΑΦΑ, τον προσδιορισμό και μελέτη των περιοχών ανακυκλοφορίας, κατανομή των πιέσεων και των διατμητικών τάσεων στο τοίχωμα της ΑΦΑ. Η μελέτη του πεδίου ροής περιλαμβάνει τη σύγκριση των υπολογιστικά λαμβανομένων μεγεθών με τα αντίστοιχα αποτελέσματα εκ της βιβλιογραφίας. Σε ένα ξεχωριστό μέρος της εργασίας αναλύονται οι ΑΦΑ και οι τεχνικές τους, οι επιπλοκές τους καθώς και τα εμβιομηχανικά χαρακτηριστικά τους. Επίσης αναλύεται η συσχέτιση των αιμοδυναμικών διαταραχών με την ανάπτυξη ινομυϊκής υπερπλασίας. / It is widely accepted that the vascular biological procedure is influenced by the local hemodynamics. Experiments in vivo, in vitro and numerical studies have confirmed that the flow models in Arteriovenous Anastomosis (AVA) depend strongly on the area geometry. This project goes through the flow distribution in “virtual geometries”of AVA using computational fluid dynamics (CFD). The term “virtual geometry” refers to a type of geometry which is not determined by calculations of real anastomosis but roughly simulates it. The boundary conditions of the problem were the velocity distributions that were calculated in specific entrance points in artery and vein of the AVA. The study of the flow distribution encompasses the velocity distribution in the whole area of the AVA, the specification and investigation of back flow areas, the distribution of pressure and shear stress in the AVA walls. It also encompasses the comparison of computated results to the equivalent measurements accumulated from the international bibliography. A separate chapter of this study refers to different kinds of AVA and their techniques, complications and biomechanical characteristics. Furthermore, it elaborates the correlations of the hemodynamical disorders and intimal hyperplasia.