Browsing by Subject "Coagulation"
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Item Open Access A handheld microfluidic device for whole blood coagulation measurement using erythrocyte aggregation(Chemical and Biological Microsystems Society, 2020) Işıksaçan, Ziya; Erel, O; Elbüken, ÇağlarWe present a portable platform that enables coagulation time measurement from a drop of whole blood at the point-of-care by optical investigation of erythrocyte aggregation. The assay was demonstrated for the evaluation of both intrinsic and extrinsic pathways of the coagulation cascade.Item Open Access Microfluidic platforms for hemorheology and coagulation time analysis(2020-01) Işıksaçan, ZiyaBlood is a non-Newtonian fluid consisting of plasma and cells that uninterruptedly circulate the body. Erythrocytes are deformable anucleated discoid blood cells with a viscoelastic membrane, constituting around half of blood volume. Hemorheology investigates blood flow characteristics determined by hemorheological properties comprising aggregation, sedimentation, and deformation of erythrocytes as well as blood/plasma viscoelasticity. These hemorheological properties are intricately interdependent. Hence, acquired or hereditary disorders affecting one hemorheological property (malaria, diabetes, anemia) lead to alterations in other properties. Available techniques lack the ability to measure these properties all-at-once and in physiologically relevant conditions. Blood coagulation is as essential as a healthy blood flow. This is a body defense mechanism involving the interplay of blood constituents for stable clot formation to stop bleeding. Sensitive and periodic measurement of coagulation time is critical for individuals who are under the risk of excessive bleeding or thrombus-originated vessel obstruction. Today, these conditions are responsible for 25 percent of all deaths worldwide. Unfortunately, the conventional practice for coagulation monitoring is fixed-interval hospital visits by patients. In this thesis, we present novel microfluidic platforms and measurement methods for the analysis of hemorheological properties and coagulation time parameters. The assays are based on optical quantification of erythrocyte dynamics inside miniaturized channels. The measurements require only 50 µl undiluted blood and are completed in less than 5 min. Firstly, we demonstrate optical measurement of erythrocyte aggregation and rapid measurement of erythrocyte sedimentation rate (ESR) using aggregation dynamics. Secondly, we present the results of clinical ESR tests performed in a local hospital and compare the performance of the developed platform with the conventional 1-hour test. Simultaneously obtained optical transmission signals and real-time microscopic observations of erythrocytes in custom-developed cartridges validate the proposed measurement principle. Thirdly, we present a method offering a holistic approach to blood flow characterization. The method enables simultaneous analysis of multiple hemorheological properties by optically investigating collective erythrocyte dynamics, primarily deformation, in a channel during unique damped oscillatory sample motion. We create a fluidic environment mimicking in vivo flow: confined, directional, and pulsatile movement of blood at flow rates and hematocrit comparable to physiological levels. Fourthly, we present a method for blood coagulation time measurement by optical quantification of erythrocyte aggregation. We demonstrate the fundamental relationship between aggregation and coagulation. Finally, we present an alternative, entirely disposable microfluidic platform for hemorheology and coagulation time analysis based on migration analysis of blood sample in microfluidic channels. Overall, the microfluidic platforms and measurement methods presented here will potentially initiate routine hemorheological and coagulation time analysis even in resource-poor setting.Item Open Access An optofluidic point-of-care device for quantitative investigation of erythrocyte aggregation during coagulation(Elsevier B.V., 2018) Işıksaçan, Ziya; Hastar, Nurcan; Erel, Ö.; Elbüken, ÇağlarCoagulation, the process leading to clot formation with the interplay of blood constituents, is a self-regulating mechanism, requiring attentive and periodic monitoring for numerous clinical cases. Erythrocyte aggregation (EA) is a characteristic behaviour of erythrocytes forming reversible clumps especially in vitro at low shear rates. The effect of EA during coagulation is overlooked in whole blood (WB) clotting assays, and the relationship between the two mechanisms is not well understood. We present an optofluidic point-of-care device enabling quantitative investigation of EA from 50 μl WB during the coagulation process. Not only did we explain the coagulation mechanism considering EA, but we also demonstrated coagulation time measurement from optical EA analysis. The device consists of a disposable cartridge and a handheld analyzer containing a pinch valve for fluid motion and optics for transmitted light measurement. Following the sample introduction and cessation of the valve operation, the optical signal is the lowest due to shear-induced cell disaggregation. Then, the signal increases due to EA until reaching a peak, indicating blood clotting. The working principle was proven through clinical tests for prothrombin time measurement. In addition to revealing the relation between coagulation and aggregation, this device is promising for rapid WB coagulation time measurement.Item Open Access Self-powered disposable prothrombin time measurement device with an integrated effervescent pump(Elsevier B.V., 2018) Güler, M. T.; Işıksaçan, Ziya; Serhatlıoğlu, Murat; Elbüken, ÇağlarCoagulation is an essential physiological activity initiated by the interaction of blood components for clot formation. Prothrombin time (PT) measurement is a clinical test for the assessment of the extrinsic/common pathways of coagulation cascade. Periodic measurement of PT is required under numerous conditions including cardiovascular disorders. We present a self-powered microfluidic device for quantitative PT measurement from 50 μl whole blood. The entire platform is disposable and does not require any external pumping, power, or readout units. It consists of a 3D-printed effervescent pump for CO2 generation from a chemical reaction, a cartridge for two-channel fluid flow (blood and water), and a grid for the quantification of fluid migration distance. Following the introduction of the fluids to the corresponding channel inlets, marking the coagulation start, an acid-base reaction is triggered for gas generation that drives the fluids within the channels. When the blood coagulates, its flow in the channel is halted. At that point, the distance water has travelled is measured using the grid. This distance correlates with PT as demonstrated through clinical tests with patient samples. This single-unit device has a potential for rapid evaluation and periodic monitoring of PT in the clinical settings and at the point-of-care.Item Open Access Template-free synthesis of organically modified silica mesoporous thin films for TNT sensing(American Chemical Society, 2010) Yildirim, A.; Budunoglu, H.; Deniz, H.; Güler, Mustafa O.; Bayındır, MehmetIn this paper, we present a facile, template-free sol−gel method to produce fluorescent and highly mesoporous organically modified silica (ORMOSIL) thin films for vapor phase sensing of TNT. An alkyltrifunctional, methyltrimethoxysilane MTMS precursor was used to impart hydrophobic behavior to gel network in order to form the spring back effect. In this way, porous films (up to 74% porosity) are obtained at ambient conditions. Fluorescent molecules are physically encapsulated in the ORMOSIL network during gelation. Fluorescence of the films was found to be stable even after 3 months, proving the successful fixing of the dye into the ORMOSIL network. The functional ORMOSIL thin films exhibited high fluorescence quenching upon exposition to TNT and DNT vapor. Fluorescence quenching responses of the films are thickness-dependent and higher fluorescence quenching efficiency was observed for the thinnest film (8.6% in 10 s). The prepared mesoporous ORMOSIL thin films have great potential in new sensor and catalysis applications.