Monitoring time course of human whole blood coagulation using a microfluidic dielectric sensor with a 3D capacitive structure

2015 ◽  
Author(s):  
Debnath Maji ◽  
Michael A. Suster ◽  
Evi Stavrou ◽  
Umut A. Gurkan ◽  
Pedram Mohseni
Keyword(s):  
Blood Coagulation ◽  
Whole Blood ◽  
Time Course ◽  
Human Whole Blood ◽  
Monitoring Time ◽  
Dielectric Sensor

Monitoring Fibrin Polymerization Effects on Whole Blood Coagulation Using a Microfluidic Dielectric Sensor

2020 ◽  
Author(s):  
Sina Pourang ◽  
Debnath Maji ◽  
Ujjal D. S. Sekhon ◽  
Anirban Sen Gupta ◽  
Michael A. Suster ◽  
...  
Keyword(s):  
Blood Coagulation ◽  
Whole Blood ◽  
Fibrin Polymerization ◽  
Dielectric Sensor

scholarly journals Conjugated Linoleic Acid Grafting Improved Hemocompatibility of the Polycaprolactone Electrospun Membrane

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Nam Minh-phuong Tran ◽  
Toan Le-duc Huynh ◽  
Binh Ngoc Phan ◽  
Nhi Ngoc-thao Dang ◽  
Thang Bach Phan ◽  
...  
Keyword(s):  
Linoleic Acid ◽  
Physical Properties ◽  
Conjugated Linoleic Acid ◽  
Blood Coagulation ◽  
Whole Blood ◽  
Negligible Effect ◽  
Medical Applications ◽  
Electrospun Membrane ◽  
Human Whole Blood ◽  
Wide Range

Polycaprolactone (PCL) is a versatile biomaterial with a wide range of medical applications, but its use in blood-contacting devices is hampered due to insufficient hemocompatibility. In this work, electrospun polycaprolactone (PCL) membranes were chemically grafted with conjugated linoleic acid (CLA) to prevent induced blood coagulation. The density of grafted CLA and its effects on the morphology and wettability of the membranes were examined. The study also investigated how the membrane interacted with human whole blood and platelets to determine its antithrombotic properties. As the results suggested, the grafting caused a negligible effect on the physical properties of the membrane but greatly improved its compatibility with blood, showing that the approach can be investigated further for blood-contacting applications.

A Circuit Model of Human Whole Blood in a Microfluidic Dielectric Sensor

2016 ◽  
Vol 63 (12) ◽  
pp. 1156-1160 ◽  
Author(s):  
Michael A. Suster ◽  
Nicholas H. Vitale ◽  
Debnath Maji ◽  
Pedram Mohseni
Keyword(s):  
Whole Blood ◽  
Circuit Model ◽  
Human Whole Blood ◽  
Dielectric Sensor

scholarly journals Comparative assessment of immune evasion mechanisms in human whole-blood infection assays by a systems biology approach

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249372
Author(s):  
Teresa Lehnert ◽  
Maria T. E. Prauße ◽  
Kerstin Hünniger ◽  
Jan-Philipp Praetorius ◽  
Oliver Kurzai ◽  
...  
Keyword(s):  
Systems Biology ◽  
Mathematical Models ◽  
Immune Evasion ◽  
Whole Blood ◽  
Time Course ◽  
Experimental Studies ◽  
Least Square ◽  
Model Quality ◽  
Human Whole Blood ◽  
Immune Mechanisms

Computer simulations of mathematical models open up the possibility of assessing hypotheses generated by experiments on pathogen immune evasion in human whole-blood infection assays. We apply an interdisciplinary systems biology approach in which virtual infection models implemented for the dissection of specific immune mechanisms are combined with experimental studies to validate or falsify the respective hypotheses. Focusing on the assessment of mechanisms that enable pathogens to evade the immune response in the early time course of a whole-blood infection, the least-square error (LSE) as a measure for the quantitative agreement between the theoretical and experimental kinetics is combined with the Akaike information criterion (AIC) as a measure for the model quality depending on its complexity. In particular, we compare mathematical models with three different types of pathogen immune evasion as well as all their combinations: (i) spontaneous immune evasion, (ii) evasion mediated by immune cells, and (iii) pre-existence of an immune-evasive pathogen subpopulation. For example, by testing theoretical predictions in subsequent imaging experiments, we demonstrate that the simple hypothesis of having a subpopulation of pre-existing immune-evasive pathogens can be ruled out. Furthermore, in this study we extend our previous whole-blood infection assays for the two fungal pathogens Candida albicans and C. glabrata by the bacterial pathogen Staphylococcus aureus and calibrated the model predictions to the time-resolved experimental data for each pathogen. Our quantitative assessment generally reveals that models with a lower number of parameters are not only scored with better AIC values, but also exhibit lower values for the LSE. Furthermore, we describe in detail model-specific and pathogen-specific patterns in the kinetics of cell populations that may be measured in future experiments to distinguish and pinpoint the underlying immune mechanisms.

scholarly journals Assessment of Hypercoagulable State in Whole Blood in Sepsis Patients Using a Novel Microfluidic Dielectric Sensor

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1882-1882
Author(s):  
Sina Pourang ◽  
Michael A Suster ◽  
Pedram Mohseni ◽  
Lalitha V Nayak
Keyword(s):  
Blood Coagulation ◽  
Whole Blood ◽  
Stock Options ◽  
Research Funding ◽  
Hypercoagulable State ◽  
Blood Samples ◽  
Healthy Donors ◽  
Dielectric Sensor ◽  
Peak Parameter ◽  
Coagulation Status

Abstract Background: There is an intimate link between inflammation and thrombosis, and patients with pro-inflammatory/infectious disorders develop a hypercoagulable state. Extant coagulation assays are unable to distinguish the pro-coagulant state of a patient's blood, require 2-3 mL of blood, and take 2-3 hours for processing. These assays are also typically examined in plasma and do not represent the contribution of blood cellular elements that participate in thrombosis in vivo. Thus, a point-of-care device for rapid, comprehensive assessment of whole blood coagulation is crucial to ensure appropriate and timely evaluation in critically ill patients. We have introduced a microfluidic sensor (ClotChip) that uses dielectric spectroscopy to provide such an assessment in a handheld platform. We have shown in clinical studies in patients with a hypocoagulable state that ClotChip is sensitive to both coagulation factor and platelet defects, allowing for a global assessment of blood coagulation status using <10 µL of whole blood and in <30 min. In this study, we optimized ClotChip to assess the blood coagulation status in patients with a hypercoagulable state. Methods: Citrated blood samples from 12 patients with a diagnosis of sepsis and 11 healthy donors as controls were obtained under an IRB-approved protocol and tested with ClotChip within 2 hours of collection. ClotChip readout curve was calculated as the temporal variation of blood dielectric permittivity at 1 MHz, and the time to reach a permittivity peak (T peak) was taken as an indicator of coagulation time based on our prior studies. To increase the sensitivity of the ClotChip T peak parameter to a hypercoagulable state, we used two different anticoagulants, recombinant thrombomodulin (rTM) and activated protein C (APC). To optimize the anticoagulant concentration, whole blood samples from healthy donors were treated in vitro with lipopolysaccharide to mimic a pro-coagulant state of blood and tested with ClotChip after adding various concentrations of rTM and APC. We concluded that a concentration of 5 µg/mL for rTM and 10 µg/mL for APC would result in an optimal change in T peak for detecting the pro-coagulant state. Since heparin (or lovenox) is routinely used in hospitalized patients, sepsis and control samples were pretreated with hepzyme at a final concentration of 2 IU/mL to reverse the heparin effect. The T peak parameter was measured and compared in (i) hepzyme only-, (ii) rTM-, and (iii) APC-treated samples. Data are reported as mean ± standard deviation. Two-tailed t test is used to test for statistical significance between groups, and P < 0.05 is considered statistically significant. In box-and-whiskers plots, the box represents the range from the first to the third quartile, the horizontal line represents the median, plus sign (+) represents mean of the data; whiskers extend to the maximum and minimum data values, and dots represent individual subject data. Results: In hepzyme only-treated samples, T peak was significantly prolonged at 478±137 sec in sepsis samples, as compared to 357±58 sec in controls (Figs. 1A, 1B). rTM treatment resulted in T peak of 503±128 sec for sepsis samples and 443±81 sec for controls, whereas APC treatment resulted in T peak of 1,095±850 sec for sepsis samples and 477±71 sec for controls (Figs. 1A, 1B). Although T peak was prolonged at baseline in hepzyme only-treated sepsis samples, no further prolongation was noted with rTM treatment (difference in T peak of 24±94 sec; Fig. 1C), as compared to rTM-treated controls (difference in T peak of 85±40 sec; Fig. 1C). However, with a difference in T peak of 616±804 sec, the APC-treated sepsis samples exhibited T peak prolongation when compared to hepzyme only-treated sepsis samples, whereas the APC-treated controls did not (difference in T peak of 119±64 sec; Fig. 1D). A comparison between the APC- and rTM-treated samples revealed a significant prolongation of T peak in sepsis samples (difference in T peak of 591±815 sec) when compared to controls (difference in T peak of 30±66 sec; Fig. 1E). Conclusions: Our studies identify a unique coagulation profile in sepsis patient blood using a microfluidic dielectric sensor. These data suggest that the addition of rTM or APC can enhance the sensitivity of the ClotChip T peak parameter for detecting the pro-coagulant state in whole blood. Ongoing studies are examining the coagulation profile in other pro-inflammatory and infectious states. Figure 1 Figure 1. Disclosures Suster: XaTek Inc.: Consultancy, Current holder of stock options in a privately-held company, Patents & Royalties, Research Funding. Mohseni: XaTek Inc.: Consultancy, Current holder of stock options in a privately-held company, Patents & Royalties, Research Funding. Nayak: BioChip Labs: Current Employment.

scholarly journals Assessment of whole blood coagulation with a microfluidic dielectric sensor

2018 ◽  
Vol 16 (10) ◽  
pp. 2050-2056 ◽  
Author(s):  
D. Maji ◽  
M. De La Fuente ◽  
E. Kucukal ◽  
U. D. S. Sekhon ◽  
A. H. Schmaier ◽  
...  
Keyword(s):  
Blood Coagulation ◽  
Whole Blood ◽  
Dielectric Sensor

Layer-by-Layer Assembly on Hydrogel Surfaces and Control of Human Whole Blood Coagulation

2003 ◽  
Vol 32 (2) ◽  
pp. 174-175 ◽  
Author(s):  
Hirokazu Sakaguchi ◽  
Takeshi Serizawa ◽  
Mitsuru Akashi
Keyword(s):  
Blood Coagulation ◽  
Whole Blood ◽  
Layer By Layer ◽  
Human Whole Blood ◽  
Layer By Layer Assembly ◽  
And Control ◽  
Layer Assembly
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