One-Step Microfluidic Purification of White Blood Cells from Whole Blood for Immunophenotyping.

One-step purification of white blood cells (WBCs) is essential to automate blood sample preparation steps for WBC analysis, but conventional methods such as red blood cell (RBC) lysis and density-gradient centrifugation typically require harsh chemical or physical treatment, followed by repeated manual washing steps. Alternative microfluidic separation methods show limited separation performances due to the trade-off between purity and throughput. Herein, an integrated microfluidic device is developed to decouple the trade-off by synergistically combining a slant array ridge-based WBC enrichment unit as a throughput enhancer and a slant, asymmetric lattice-based WBC washing unit as a purity enhancer. The enrichment unit can maintain a high sample-infusion throughput while lowering the flow rate into the washing unit, thus enabling WBC-selective washing without significant influence by the overwhelming number of RBCs and inertial forces. The device delivers efficient separation performances by rejecting 99.9% of RBCs as well as 99.9% of blood plasma from canine and human whole blood in a single round of purification at a high throughput of 60 µL/min. The purified WBC population well preserves the composition of lymphocyte subpopulations, the major components of the adaptive immune system, thus providing the potential for the integrated device to be used as an essential sample-preparation tool for immunologic investigations.

Detection of measles vaccine virus and measles-specific immunoglobulin M in children vaccinated against measles-mumps-rubella during measles outbreak.

Information regarding the detection perioid of measles vaccine virus (MeVV) RNA in human nasopharyngeal samples and measles-specific antibodies following measles-mumps-rubella (MMR) vaccination is limited. During contact tracing for a measles outbreak at a hospital in Republic of Korea, 4 out of 206 children vaccinated with MMR underwent real-time RT-PCR assay for measles and measles-specific antibodies test. Measles virus RNA was detected in 2 children, all of which was vaccine virus strain RNA (genotype A). In a healthy 27-month-old boy, MeVV RNA was detected 448 days after MMR vaccination. Measles-specific IgM was positive 1097 days following vaccination in a 4-year-old girl. MeVV RNA and measles-specific IgM were detected for a considerable period following primary MMR vaccination. Physicians should exercise caution when interpreting positive RT-PCR results for MeVV or measles-specific IgM from a child with measles-associated symptoms who has been recently vaccinated against measles.

Correlation of brain tissue volume loss with inflammatory biomarkers IL1ß, P-tau, T-tau, and NLPR3 in the aging cognitively impaired population.

Background: Blood inflammatory biomarkers have emerged as important tools for diagnosing, assessing treatment responses, and predicting neurodegenerative diseases. This study evaluated the associations between blood inflammatory biomarkers and brain tissue volume loss in elderly people. Methods: This study included 111 participants (age 67.86 ± 8.29 years; 32 men and 79 women). A battery of the following blood inflammatory biomarkers was measured, including interleukin 1-beta (IL1ß), NACHT, LRR, and PYD domains-containing protein 3 (NLRP3), monomer Aß42 (mAß), oligomeric Aß42 (oAß), miR155, neurite outgrowth inhibitor A (nogo-A), phosphorylated tau (P-tau), and total tau (T-tau). Three-dimensional T1-weight images (3D T1WI) of all participants were prospectively obtained and segmented into gray matter and white matter to measure the gray matter volume (GMV), white matter volume (WMV), and gray-white matter boundary tissue volume (gwBTV). The association between blood biomarkers and tissue volumes was assessed using voxel-based and region-of-interest analyses. Results: GMV and gwBTV significantly decreased as the levels of IL1ß and T-tau increased, while no significant association was found between the level of P-tau and the three brain tissue volumes. Three brain tissue volumes were negatively correlated with the levels of IL1ß, P-tau, and T-tau in the hippocampus. Specifically, IL1ß and T-tau levels showed a distinct negative association with the three brain tissue volume losses in the hippocampus. In addition, gwBTV was negatively associated with the level of NLRP3. Conclusion: The observed association between brain tissue volume loss and elevated levels of IL1ß and T-tau suggests that these biomarkers in the blood may serve as potential biomarkers of cognitive impairment in elderly people. Thus, IL1ß and T-tau could be used to assess disease severity and monitor treatment response after diagnosis in elderly people who are at risk of cognitive decline.

Relationship between Brain Tissue Changes and Blood Biomarkers of Cyclophilin A, Heme Oxygenase-1, and Inositol-Requiring Enzyme 1 in Patients with Alzheimer's Disease.

Cyclophilin A (CypA), heme oxygenase-1 (HO-1), and inositol-requiring enzyme 1 (IRE1) are believed to be associated with Alzheimer's disease (AD). In this study, we investigated the association between gray matter volume (GMV) changes and blood levels of CypA, HO-1, and IRE1 in cognitively normal (CN) subjects and those with amnestic mild cognitive impairment (aMCI) and AD. Forty-five elderly CN, 34 aMCI, and 39 AD subjects were enrolled in this study. The results of voxel-based multiple regression analysis showed that blood levels of CypA, HO-1, and IRE1 were correlated with GMV on brain magnetic resonance imaging (MRI) in the entire population (p = 0.0005). The three serum protein levels were correlated with GMV of signature AD regions in the population as a whole. CypA values increased with increasing GMV in the occipital gyrus (r = 0.387, p < 0.0001) and posterior cingulate (r = 0.196, p = 0.034). HO-1 values increased with increasing GMV at the uncus (r = 0.307, p = 0.0008), lateral globus pallidus and putamen (r = 0.287, p = 0.002), and hippocampus (r = 0.197, p = 0.034). IRE1 values decreased with increasing GMV at the uncus (r = -0.239, p = 0.010) and lateral globus pallidus and putamen (r = -0.335, p = 0.0002). Associations between the three serum protein levels and regional GMV indicate that the blood levels of these biomarkers may reflect the pathological mechanism of AD in the brain.

Development and evaluation of a T1 standard brain template for Alzheimer disease.

BACKGROUND: Patients with Alzheimer disease (AD) and mild cognitive impairment (MCI) have high variability in brain tissue loss, making it difficult to use a disease-specific standard brain template. The objective of this study was to develop an AD-specific three-dimensional (3D) T1 brain tissue template and to evaluate the characteristics of the populations used to form the template. METHODS: We obtained 3D T1-weighted images from 294 individuals, including 101 AD, 96 amnestic MCI, and 97 cognitively normal (CN) elderly individuals, and segmented them into different brain tissues to generate AD-specific brain tissue templates. Demographic data and clinical outcome scores were compared between the three groups. Voxel-based analyses and regions-of-interest-based analyses were performed to compare gray matter volume (GMV) and white matter volume (WMV) between the three participant groups and to evaluate the relationship of GMV and WMV loss with age, years of education, and Mini-Mental State Examination (MMSE) scores. RESULTS: We created high-resolution AD-specific tissue probability maps (TPMs). In the AD and MCI groups, losses of both GMV and WMV were found with respect to the CN group in the hippocampus (F >44.60, P<0.001). GMV was lower with increasing age in all individuals in the left (r=-0.621, P<0.001) and right (r=-0.632, P<0.001) hippocampi. In the left hippocampus, GMV was positively correlated with years of education in the CN groups (r=0.345, P<0.001) but not in the MCI (r=0.223, P=0.0293) or AD (r=-0.021, P=0.835) groups. WMV of the corpus callosum was not significantly correlated with years of education in any of the three subject groups (r=0.035 and P=0.549 for left, r=0.013 and P=0.821 for right). In all individuals, GMV of the hippocampus was significantly correlated with MMSE scores (left, r=0.710 and P<0.001; right, r=0.680 and P<0.001), while WMV of the corpus callosum showed a weak correlation (left, r=0.142 and P=0.015; right, r=0.123 and P=0.035). CONCLUSIONS: A 3D, T1 brain tissue template was created using imaging data from CN, MCI, and AD participants considering the participants' age, sex, and years of education. Our disease-specific template can help evaluate brains to promote early diagnosis of MCI individuals and aid treatment of MCI and AD individuals.

Application of metallic nanoparticle-biochars with ionic liquids for thermal transfer fluids.

Ionic liquids (ILs (1-butyl-3-methylimidazolium chloride ([C4mim][Cl]) and 1-butyl-3-methylimidazolium tetrafluoroborate ([C4mim][BF4]))) were used as heat transfer fluids for solar thermal collectors. The additive of ILs was biochar containing copper and silver nanoparticles (Cu-Ag/biochar) to improve the adsorption of solar irradiation and thermal conductivities. After impregnation and reduction processes, nanoparticles such as Cu, CuO, Cu(OH)2, Ag, and Ag2O were found in the biochar by X-ray powder diffraction (XRD) spectroscopy. With adding 2% Cu-Ag/biochar into the ILs, the thermal conductivities of [C4mim][Cl] and [C4mim][BF4] containing 10% Cu-1% Ag/biochar were individually increased 9.2 and 6.6 times compared to the base ILs due to the high graphitization of biochar and metallic nanoparticles. The 1H NMR (nuclear magnetic resonance) features of the imidazole ring and methyl group in the ILs were highly disturbed due to the formation of weak or strong hydrogen bonds between the cations in ILs and Cu-Ag/biochar. The high hydrogen bond acceptance of anions in ILs also affected the thermal properties. The thermal properties of the metals/biochar [C4mim][Cl] were better than those of metals/biochar [C4mim][BF4] due to high hydrogen bond acceptance of [Cl]-. The strong hydrogen bonds between the Cu-Ag/biochar and the cations and anions in ILs result in thermal properties of heat transfer fluids. Under simulated sunlight, the temperatures of [C4mim][Cl] and [C4mim][BF4] containing 10% Cu-1% Ag/biochar rose from 304 to 345 and 340 K within 24 min, respectively. A novel heat transfer fluid was developed for high adsorption of irradiation, high thermal conductivities, and speedy transfer of heat.