dynamic-multiparameter-platelet-function-assessment-using-capacitive

Dynamic Multiparameter Platelet Function Assessment Using a Capacitive Biosensor

Platelets play a fundamental role in blood clotting through a series of regulated responses, including adhesion, spreading, granular secretion, ...

University of Washington

An improved thermal-needle approach for accurate and fast measurement of thermal conductivity of aqueous and soft biomaterials was developed using microfabricated thermal conductivity sensors. This microscopic measuring device was comprehensively characterized at temperatures from 0 °C to 40 °C. Despite the previous belief, system calibration constant was observed to be highly temperature-dependent. Dynamic thermal conductivity response during cooling (40 °C to -40 °C) was observed using the miniaturized single tip sensor for various concentrations of CPAs, i.e., glycerol, ethylene glycol and dimethyl sulfoxide. Chicken breast, chicken skin, porcine limb, and bovine liver were assayed to investigate the effect of anatomical heterogeneity on thermal conductivity using the arrayed multi-tip sensor at 20 °C. Experimental results revealed distinctive differences in localized thermal conductivity, which suggests the use of approximated or constant property values is expected to bring about results with largely inflated uncertainties when investigating bio-heat transfer mechanisms and/or performing sophisticated thermal modeling with complex biological tissues. Overall, the presented micro thermal sensor with automated data analysis algorithm is a promising approach for direct thermal conductivity measurement of aqueous solutions and soft biomaterials and is of great value to cryopreservation of tissues, hyperthermia or cryogenic, and other thermal-based clinical diagnostics and treatments.

High accuracy thermal conductivity measurement of aqueous cryoprotective agents and semi-rigid biological tissues using a microfabricated thermal sensor.

The lack of an effective rewarming technique restricted the successful cryopreservation of organ or large tissues by vitrification. The conversion of electromagnetic (EM) energy into heat provides a possible solution for the rewarming process for the cryopreservation. In this work, an EM resonance rewarming system was set up with dynamic feedback control and power feeding optimization. In addition, we take advantage of magnetic nanoparticles (MNPs) to absorb magnetic field energy to further enhance the energy conversion efficiency. We achieved a >200 °C min rewarming rate for tens of milliliters of cryopreserved samples. Besides, we also investigated the effect of nanoparticle size and concentration based on thermal properties by analyzing the contribution of nanoparticles and the utilization of field energy. The closed system reduced the possible concomitant side effects when increasing the number of nanoparticles or increasing the EM source power. With the remarkably low dosage of nanoparticles (0.1 mg mL Fe) compared to that for other MNP-based rewarming applications, this study opens the door to new approaches for exploring novel techniques for tissue and organ preservation.

Investigation of Electromagnetic Resonance Rewarming Enhanced by Magnetic Nanoparticles for Cryopreservation.

The Jurkat cell is an immortalized line of human acute lymphocyte leukemia cells that is widely used in the study of adoptive cell therapy, a novel treatment of several advanced forms of cancer. The ability to transport water and solutes across the cell membrane under different temperatures is an important factor for deciding the specific protocol for cryopreservation of the Jurkat cell. In this study we propose a comprehensive process for determination of membrane transport properties of Jurkat cell. using a novel microfluidic controlled single cell-trapping system. The osmotic behavior of an individual Jurkat cell to water and dimethyl sulfoxide (DMSO), a commonly used cryoprotective agent (CPA), under constant temperature, was recorded under a microscope utilizing the modified microfluidic system. The images of the Jurkat cell under osmotic change were processed to obtain a relationship between cell volume change and time. The experimental results were fitted using a two-parameter transport numeric model to calculate the Jurkat cell membrane permeability to water and DMSO at room temperature (22 °C). This model and the calculated parameters can help scientists optimize the cryopreservation protocol for any cell type with optimal cryoprotective agents and cooling rate for future experiments.

Determination of the Membrane Transport Properties of Jurkat Cells with a Microfluidic Device.

Rapid and accurate clinical assessment of hemostasis is essential for managing patients who undergo invasive procedures, experience hemorrhages, or receive antithrombotic therapies. Hemostasis encompasses an ensemble of interactions between the cellular and non-cellular blood components, but current devices assess only partial aspects of this complex process. In this work, we describe the development of a new approach to simultaneously evaluate coagulation function, platelet count or function, and hematocrit using a carbon nanotube-paper composite (CPC) capacitance sensor. CPC capacitance response to blood clotting at 1.3 MHz provided three sensing parameters with distinctive sensitivities towards multiple clotting elements. Whole blood-based hemostasis assessments were conducted to demonstrate the potential utility of the developed sensor for various hemostatic conditions, including pathological conditions, such as hemophilia and thrombocytopenia. Results showed good agreements when compared to a conventional thromboelastography. Overall, the presented CPC capacitance sensor is a promising new biomedical device for convenient non-contact whole-blood based comprehensive hemostasis evaluation.

Simultaneous multiparameter whole blood hemostasis assessment using a carbon nanotube-paper composite capacitance sensor.

An accurate and comprehensive assessment of platelet function is essential for managing patients who receive antiplatelet therapies or require platelet transfusion either for treating active bleeding or for prophylaxis. Platelets contribute to clotting by undergoing a series of highly regulated functional responses including adhesion, spreading, granular secretion, aggregation, and cytoskeletal contraction. However, current platelet function assays evaluate only partial aspects of this intricate process and often under non-physiological testing conditions. Herein, we describe the development of a new approach to measure multiple key platelet function-related parameters, in a more physiologically relevant ex vivo semi-rigid microenvironment using a membrane capacitance sensor (MCS). MCS response to clotting provided three sensing parameters with sensitivities towards platelet counts, stimulation strengths, and activation pathways. Live confocal fluorescent imaging of stimulated platelets on MCS suggests that the presented system can readily and accurately convert the dynamics of cytoskeletal reorganization into analyzable electrical signals. Together, this new completely electrical sensing platform can be a promising diagnostic venue to recognize the impairment of primary hemostatic functions, evaluate the efficacy of therapeutic interventions, and gain further insights into the mechanisms of platelets in hemostasis and thrombosis.

Article	Year
High accuracy thermal conductivity measurement of aqueous cryoprotective agents and semi-rigid biological tissues using a microfabricated thermal sensor. Scientific reports\| PubMed ID: 25993037	2015
Investigation of Electromagnetic Resonance Rewarming Enhanced by Magnetic Nanoparticles for Cryopreservation. Langmuir : the ACS journal of surfaces and colloids\| PubMed ID: 30550289	2019
Determination of the Membrane Transport Properties of Jurkat Cells with a Microfluidic Device. Micromachines\| PubMed ID: 31795446	2019
Simultaneous multiparameter whole blood hemostasis assessment using a carbon nanotube-paper composite capacitance sensor. Biosensors & bioelectronics\| PubMed ID: 34801797	2022
Comprehensive multiparameter evaluation of platelet function using a highly sensitive membrane capacitance sensor. Biosensors & bioelectronics\| PubMed ID: 36924685	2023

Praveen K. Sekar

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