This paper describes the design, fabrication, and testing of a microfluidic sensor for dielectric spectroscopy (DS) of human whole blood during coagulation. The sensor, termed ClotChip, employs a three-dimensional (3D), parallel-plate, capacitive sensing structure with a floating electrode integrated into a microfluidic channel. Interfaced with an impedance analyzer, the ClotChip measures the complex relative dielectric permittivity, εr, of human whole blood in a frequency range of 40Hz to 100MHz. The temporal variation in the real part of the blood dielectric permittivity at 1MHz features a time to reach a permittivity peak, Tpeak, as well as a maximum change in permittivity after the peak, Δεr,max, as two distinct parameters of ClotChip readout. The ClotChip performance was benchmarked against rotational thromboelastometry (ROTEM) to evaluate the clinical utility of its readout parameters in capturing the clotting dynamics arising from coagulation factors and platelet activity. Tpeak exhibited a very strong positive correlation (r = 0.99, p < 0.0001) with the ROTEM clotting time (CT) parameter, whereas Δεr,max exhibited a strong positive correlation (r = 0.85, p < 0.001) with the ROTEM maximum clot firmness (MCF) parameter. This work demonstrates the ClotChip potential as a point-of-care (POC) platform to assess the complete hemostatic process using <10μL of human whole blood.

Background Rapid point-of-care (POC) assessment of hemostasis is clinically important in patients with a variety of coagulation factor and platelet defects who have bleeding disorders. Objective To evaluate a novel dielectric microsensor, termed ClotChip, which is based on the electrical technique of dielectric spectroscopy for rapid, comprehensive assessment of whole blood coagulation. Methods The ClotChip is a three-dimensional, parallel-plate, capacitive sensor integrated into a single-use microfluidic channel with miniscule sample volume (< 10 μL). The ClotChip readout is defined as the temporal variation in the real part of dielectric permittivity of whole blood at 1 MHz. Results The ClotChip readout exhibits two distinct parameters, namely, the time to reach a permittivity peak (T ) and the maximum change in permittivity after the peak (Δε ), which are, respectively, sensitive towards detecting non-cellular (i.e. coagulation factor) and cellular (i.e. platelet) abnormalities in the hemostatic process. We evaluated the performance of ClotChip using clinical blood samples from 15 healthy volunteers and 12 patients suffering from coagulation defects. The ClotChip T parameter exhibited superior sensitivity at distinguishing coagulation disorders as compared with conventional screening coagulation tests. Moreover, the ClotChip Δε parameter detected platelet function inhibition induced by aspirin and exhibited strong positive correlation with light transmission aggregometry. Conclusions This study demonstrates that ClotChip assesses multiple aspects of the hemostatic process in whole blood on a single disposable cartridge, highlighting its potential as a POC platform for rapid, comprehensive hemostatic analysis.

Alterations in the deformability of red blood cells (RBCs), occurring in hemolytic blood disorders such as sickle cell disease (SCD), contributes to vaso-occlusion and disease pathophysiology. However, there are few...

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This paper reports on the design, fabrication, and testing of a microfluidic sensor for dielectric spectroscopy (DS) of human whole blood during coagulation. The sensor employs a three-dimensional (3D), parallel-plate, capacitive sensing structure with a floating electrode integrated into a microfluidic channel. Using an impedance analyzer and after a 5-point calibration, the sensor is shown to measure the real part of complex relative dielectric permittivity of human whole blood in a frequency range of 10kHz to 100MHz. The temporal variation of dielectric permittivity at 1MHz for human whole blood from three different healthy donors shows a peak in permittivity at ~ 4 to 5 minutes, which also corresponds to the onset of CaCl2-initiated coagulation of the blood sample verified visually.

Background: Reliable monitoring of coagulation factor replacement therapy in patients with severe haemophilia, especially those with inhibitors, is an unmet clinical need. While useful, global assays, eg thromboelastography (TEG), rotational thromboelastometry (ROTEM) and thrombin generation assay (TGA), are cumbersome to use and not widely available.Objective: To assess the utility of a novel, point-of-care, dielectric microsensor -ClotChip -to monitor coagulation factor replacement therapy in patients with haemophilia A, with and without inhibitors. Methods:The ClotChip T peak parameter was assessed using whole-blood samples from children with severe haemophilia A, with (n = 6) and without (n = 12) inhibitors, collected pre-and postcoagulation factor replacement therapy. ROTEM, TGA and chromogenic FVIII assays were also performed. Healthy children (n = 50) served as controls.Results: ClotChip T peak values exhibited a significant decrease for samples collected postcoagulation factor replacement therapy as compared to baseline (pretherapy) samples in patients with and without inhibitors. A difference in T peak values was also noted at baseline among severe haemophilia A patients with inhibitors as compared to those without inhibitors. ClotChip T peak parameter exhibited a very strong correlation with clotting time (CT) of ROTEM, endogenous thrombin potential (ETP) and peak thrombin of TGA, and FVIII clotting activity. Conclusions:ClotChip is sensitive to coagulation factor replacement therapy in patients with severe haemophilia A, with and without inhibitors. ClotChip T peak values correlate very well with ROTEM, TGA and FVIII assays, opening up possibilities for its use in personalized coagulation factor replacement therapy in haemophilia. K E Y W O R D Sblood coagulation tests, factor VIII, hemophilia A, point-of-care testing

Background There are acute settings where assessing the anticoagulant effect of direct oral anticoagulants (DOACs) can be useful. Due to variability among routine coagulation tests, there is an unmet need for an assay that detects DOAC effects within minutes in the laboratory or at the point of care. Methods We developed a novel dielectric microsensor, termed ClotChip, and previously showed that the time to reach peak permittivity (T peak) is a sensitive parameter of coagulation function. We conducted a prospective, single-center, pilot study to determine its clinical utility at detecting DOAC anticoagulant effects in whole blood. Results We accrued 154 individuals: 50 healthy volunteers, 49 rivaroxaban patients, 47 apixaban, and 8 dabigatran patients. Blood samples underwent ClotChip measurements and plasma coagulation tests. Control mean T peak was 428 seconds (95% confidence interval [CI]: 401–455 seconds). For rivaroxaban, mean T peak was 592 seconds (95% CI: 550–634 seconds). A receiver operating characteristic curve showed that the area under the curve (AUC) predicting rivaroxaban using T peak was 0.83 (95% CI: 0.75–0.91, p < 0.01). For apixaban, mean T peak was 594 seconds (95% CI: 548–639 seconds); AUC was 0.82 (95% CI: 0.73–0.91, p < 0.01). For dabigatran, mean T peak was 894 seconds (95% CI: 701–1,086 seconds); AUC was 1 (p < 0.01). Specificity for all DOACs was 88%; sensitivity ranged from 72 to 100%. Conclusion This diagnostic study using samples from “real-world” DOAC patients supports that ClotChip exhibits high sensitivity at detecting DOAC anticoagulant effects in a disposable portable platform, using a miniscule amount of whole blood (<10 µL).

Neural activity that occur during motor movement, speech, thought, and various other events can be observed in the form of brainwaves composed of synchronized electrical pulses emitted from adjoining communicative neurons. Observations of these brainwaves have been made possible through neurodevices, which can detect changes in electrical and/or mechanical parameters. For decades, the field of neuroscience has been enriched by the utilization of neurotechnologies at the microscale, which has begun to gain further enhancement with the introduction of nanotechnology. For example, microelectrodes were initially used for only extracellular measurements, but over the past decade, developments have been made to also record intracellular signals. Likewise, nanoknives, which gained popularity due to their versatility, can now be used for both fabricating bio-Micro-Electro-Mechanical Systems (MEMS) and also as a neurosurgery tool. Thus, considerable efforts have been made over the years to make micro- and nanosystems reliable, accurate, and sensitive to neural activity. In the late 20th century, several sophisticated technologies, including magnetic resonance imaging (MRI), computed tomography (CT), and intracranial pressure (ICP) monitoring have been integrated with MEMS. Furthermore, existing biotechnologies are being miniaturized at both the system and component level. For example, there is a remarkable interest in the field of neuroscience to utilize microfluidic technology as a diagnostic tool using specimens such as cerebrospinal fluid (CSF). Microfluidic devices are also employed as biocompatible drug delivery systems to target cells, tissues, and organs. This paper summarizes the recent developments in micro- and nano-scale neurotechnologies, including devices, fabrication processes, detection methods, their implementation challenges, in neural stimulation, monitoring, and drug delivery. This review discusses recent developments in micro and nanotechnologies, fabrication methods, and their implementation in neuroimaging, neurostimulation, monitoring of neural activities, and neural drug delivery.