Dean vortex-enhanced blood plasma separation in self-driven spiral microchannel flow with cross-flow microfilters.

Point-of-care (POC) diagnostic devices have been developing rapidly in recent years, but they are mainly using saliva instead of blood as a test sample. A highly efficient self-separation during the self-driven flow without power systems is desired for expanding the point-of-care diagnostic devices. Microfiltration stands out as a promising technique for blood plasma separation but faces limitations due to blood cell clogging, resulting in reduced separation speed and efficiency. These limitations are mainly caused by the high viscosity and hematocrit in the blood flow. A small increment in the hematocrit of the blood significantly increases the pressure needed for the blood plasma separation in the micro-filters and decreases the separation speed and efficiency. Addressing this challenge, this study explores the feasibility of diluting whole blood within a microfluidic device without external power systems. This study implemented a spiral microchannel utilizing the inertial focusing and Dean vortex effects to focus the red blood cells and extract the blood with lower hematocrit. The inertial migration of the particles during the capillary flow was first investigated experimentally; a maximum of 88% of the particles migrated to the bottom and top equilibrium positions in the optimized 350 × 60 µm (cross-sectional area, 5.8 aspect ratio) microchannel. With the optimized dimension of the microchannel, the whole blood samples within the physiological hematocrit range were tested in the experiments, and more than 10% of the hematocrit reduction was compared between the outer branch outlet and inner branch outlet in the 350 × 60 µm microchannel.

Correction: Mahmoudi et al. Solvent-Induced Formation of Novel Ni(II) Complexes Derived from Bis-Thiosemicarbazone Ligand: An Insight from Experimental and Theoretical Investigations. Int. J. Mol. Sci. 2021, 22, 5337.

We received a complaint from the Université Catholique de Louvain [...].

Microfluidic-Based Novel Optical Quantification of Red Blood Cell Concentration in Blood Flow.

The optical quantification of hematocrit (volumetric percentage of red blood cells) in blood flow in microfluidic systems provides enormous help in designing microfluidic biosensing platforms with enhanced sensitivity. Although several existing methods, such as centrifugation, complete blood cell count, etc., have been developed to measure the hematocrit of the blood at the sample preparation stage, these methods are impractical to measure the hematocrit in dynamic microfluidic blood flow cases. An easy-to-access optical method has emerged as a hematocrit quantification technique to address this limitation, especially for the microfluidic-based biosensing platform. A novel optical quantification method is demonstrated in this study, which can measure the hematocrit of the blood flow at a targeted location in a microchannel at any given instant. The images of the blood flow were shot using a high-speed camera through an inverted transmission microscope at various light source intensities, and the grayscale of the images was measured using an image processing code. By measuring the average grayscale of the images of blood flow at different luminous exposures, a relationship between hematocrit and grayscale has been developed. The quantification of the hematocrit in the microfluidic system can be instant and easy with this method. The innovative proposed technique has been evaluated with porcine blood samples with hematocrit ranging from 5% to 70%, flowing through 1000 µm wide and 100 µm deep microchannels. The experimental results obtained strongly supported the proposed optical technique of hematocrit measurement in microfluidic systems.

Blood Plasma Self-Separation Technologies during the Self-Driven Flow in Microfluidic Platforms.

Blood plasma is the most commonly used biofluid in disease diagnostic and biomedical analysis due to it contains various biomarkers. The majority of the blood plasma separation is still handled with centrifugation, which is off-chip and time-consuming. Therefore, in the Lab-on-a-chip (LOC) field, an effective microfluidic blood plasma separation platform attracts researchers' attention globally. Blood plasma self-separation technologies are usually divided into two categories: active self-separation and passive self-separation. Passive self-separation technologies, in contrast with active self-separation, only rely on microchannel geometry, microfluidic phenomena and hydrodynamic forces. Passive self-separation devices are driven by the capillary flow, which is generated due to the characteristics of the surface of the channel and its interaction with the fluid. Comparing to the active plasma separation techniques, passive plasma separation methods are more considered in the microfluidic platform, owing to their ease of fabrication, portable, user-friendly features. We propose an extensive review of mechanisms of passive self-separation technologies and enumerate some experimental details and devices to exploit these effects. The performances, limitations and challenges of these technologies and devices are also compared and discussed.

COVID-19 Biomarkers and Advanced Sensing Technologies for Point-of-Care (POC) Diagnosis.

COVID-19, also known as SARS-CoV-2 is a novel, respiratory virus currently plaguing humanity. Genetically, at its core, it is a single-strand positive-sense RNA virus. It is a beta-type Coronavirus and is distinct in its structure and binding mechanism compared to other types of coronaviruses. Testing for the virus remains a challenge due to the small market available for at-home detection. Currently, there are three main types of tests for biomarker detection: viral, antigen and antibody. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) remains the gold standard for viral testing. However, the lack of quantitative detection and turnaround time for results are drawbacks. This manuscript focuses on recent advances in COVID-19 detection that have lower limits of detection and faster response times than RT-PCR testing. The advancements in sensing platforms have amplified the detection levels and provided real-time results for SARS-CoV-2 spike protein detection with limits as low as 1 fg/mL in the Graphene Field Effect Transistor (FET) sensor. Additionally, using multiple biomarkers, detection levels can achieve a specificity and sensitivity level comparable to that of PCR testing. Proper biomarker selection coupled with nano sensing detection platforms are key in the widespread use of Point of Care (POC) diagnosis in COVID-19 detection.

Modeling Focused-Ultrasound Response for Non-Invasive Treatment Using Machine Learning.

The interactions between body tissues and a focused ultrasound beam can be evaluated using various numerical models. Among these, the Rayleigh-Sommerfeld and angular spectrum methods are considered to be the most effective in terms of accuracy. However, they are computationally expensive, which is one of the underlying issues of most computational models. Typically, evaluations using these models require a significant amount of time (hours to days) if realistic scenarios such as tissue inhomogeneity or non-linearity are considered. This study aims to address this issue by developing a rapid estimation model for ultrasound therapy using a machine learning algorithm. Several machine learning models were trained on a very-large dataset (19,227 simulations), and the performance of these models were evaluated with metrics such as Root Mean Squared Error (RMSE), R-squared (R2), Akaike Information Criterion (AIC), and Bayesian Information Criterion (BIC). The resulted random forest provides superior accuracy with an R2 value of 0.997, an RMSE of 0.0123, an AIC of -82.56, and a BIC of -81.65 on an external test dataset. The results indicate the efficacy of the random forest-based model for the focused ultrasound response, and practical adoption of this approach will improve the therapeutic planning process by minimizing simulation time.

Solvent-Induced Formation of Novel Ni(II) Complexes Derived from Bis-Thiosemicarbazone Ligand: An Insight from Experimental and Theoretical Investigations.

In this work, we report solvent-induced complexation properties of a new N2S2 tetradentate bis-thiosemicarbazone ligand (H2LI), prepared by the condensation of 4-phenylthiosemicarbazide with bis-aldehyde, namely 2,2'-(ethane-1,2-diylbis(oxy)dibenzaldehyde, towards nickel(II). Using ethanol as a reaction medium allowed the isolation of a discrete mononuclear homoleptic complex [NiLI] (1), for which its crystal structure contains three independent molecules, namely 1-I, 1-II, and 1-III, in the asymmetric unit. The doubly deprotonated ligand LI in the structure of 1 is coordinated in a cis-manner through the azomethine nitrogen atoms and the thiocarbonyl sulfur atoms. The coordination geometry around metal centers in all the three crystallographically independent molecules of 1 is best described as the seesaw structure. Interestingly, using methanol as a reaction medium in the same synthesis allowed for the isolation of a discrete mononuclear homoleptic complex [Ni(LII)2] (2), where LII is a monodeprotonated ligand 2-(2-(2-(2-(dimethoxymethyl)phenoxy)ethoxy)benzylidene)-N-phenylhydrazine-1-carbothioamide (HLII). The ligand LII was formed in situ from the reaction of LI with methanol upon coordination to the metal center under synthetic conditions. In the structure of 2, two ligands LII are coordinated in a trans-manner through the azomethine nitrogen atom and the thiocarbonyl sulfur atom, also yielding a seesaw coordination geometry around the metal center. The charge and energy decomposition scheme ETS-NOCV allows for the conclusion that both structures are stabilized by a bunch of London dispersion-driven intermolecular interactions, including predominantly N-H∙∙∙S and N-H∙∙∙O hydrogen bonds in 1 and 2, respectively; they are further augmented by less typical C-H∙∙∙X (where X = S, N, O, π), CH∙∙∙HC, π∙∙∙π stacking and the most striking, attractive long-range intermolecular C-H∙∙∙Ni preagostic interactions. The latter are found to be determined by both stabilizing Coulomb forces and an exchange-correlation contribution as revealed by the IQA energy decomposition scheme. Interestingly, the analogous long-range C-H∙∙∙S interactions are characterized by a repulsive Coulomb contribution and the prevailing attractive exchange-correlation constituent. The electron density of the delocalized bonds (EDDB) method shows that the nickel(II) atom shares only ~0.8|e| due to the σ-conjugation with the adjacent in-plane atoms, demonstrating a very weak σ-metalloaromatic character.

Detection of cancer antigens (CA-125) using gold nano particles on interdigitated electrode-based microfluidic biosensor.

Integrating microfluidics with biosensors is of great research interest with the increasing trend of lab-on-the chip and point-of-care devices. Though there have been numerous studies performed relating microfluidics to the biosensing mechanisms, the study of the sensitivity variation due to microfluidic flow is very much limited. In this paper, the sensitivity of interdigitated electrodes was evaluated at the static drop condition and the microfluidic flow condition. In addition, this study demonstrates the use of gold nanoparticles to enhance the sensor signal response and provides experimental results of the capacitance difference during cancer antigen-125 (CA-125) antigen-antibody conjugation at multiple concentrations of CA-125 antigens. The experimental results also provide evidence of disease-specific detection of CA-125 antigen at multiple concentrations with the increase in capacitive signal response proportional to the concentration of the CA-125 antigens. The capacitive signal response of antigen-antibody conjugation on interdigitate electrodes has been enhanced by approximately 2.8 times (from 260.80 to 736.33 pF at 20 kHz frequency) in static drop condition and approximately 2.5 times (from 205.85 to 518.48 pF at 20 kHz frequency) in microfluidic flow condition with gold nanoparticle-coating. The capacitive signal response is observed to decrease at microfluidic flow condition at both plain interdigitated electrodes (from 260.80 to 205.85 pF at 20 kHz frequency) and gold nano particle coated interdigitated electrodes (from 736.33 to 518.48 pF at 20 kHz frequency), due to the strong shear effect compared to static drop condition. However, the microfluidic channel in the biosensor has the potential to increase the signal to noise ratio due to plasma separation from the whole blood and lead to the increase concentration of the biomarkers in the blood volume for sensing.