Biofluid dynamics

Plasma proteins are considered the most informative source of biomarkers for disease diagnosis and monitoring. Mass spectrometry (MS)-based proteomics has been applied to identify biomarkers in plasma, but the complexity of the plasma proteome and the extremely large dynamic range of protein abundances in plasma make the clinical application of plasma proteomics highly challenging. We designed and synthesized zeolite-based nanoparticles to deplete high-abundance plasma proteins. The resulting novel plasma proteomic assay can measure approximately 3000 plasma proteins in a 45 min chromatographic gradient...

Sweating regulates the body temperature in extreme environments or during exercise. Here, we investigate the evaporative heat transfer of a sweat droplet at the microscale to unveil how the evaporation complexity of a sweat droplet would affect the body's ability to cool under specific environmental conditions. Our findings reveal that, depending on the relative humidity and temperature levels, sweat droplets experience imperfect evaporation dynamics, whereas water droplets evaporate perfectly at equivalent ambient conditions...

Developing an easy-to-use and non-invasive sensor for monitoring progesterone (P4) as a multi-functional hormone is highly demanded for point-of-care testing. In this study, an ultrasensitive electrochemical aptasensor is fabricated for monitoring P4 in human biofluids. The sensing interface was designed based on the porous nitrogen-doped hollow carbon spheres (N-HCSs). The N-HCSs covalently immobilized high-dense aptamer (Apt) sequences as the bioreceptor of P4. The electron transfer of the redox probe was hindered by incubating P4 on the aptasensor surface and forming the P4-Apt complexes...

Despite progress, MS-based proteomics in biofluids, especially blood, faces challenges such as dynamic range and throughput limitations in biomarker and disease studies. In this work, we used cutting-edge proteomics technologies to construct label-based and label-free workflows, capable of quantifying approximately 2,000 proteins in biofluids. With 70µL of blood and a single depletion strategy, we conducted an analysis of a homogenous cohort (n = 32), comparing medium-grade prostate cancer patients (Gleason score: 7(3 + 4); TNM stage: T2cN0M0, stage IIB) to healthy donors...

Can insects weighing mere grams challenge our current understanding of fluid dynamics in urination, jetting fluids like their larger mammalian counterparts? Current fluid urination models, predominantly formulated for mammals, suggest that jetting is confined to animals over 3 kg, owing to viscous and surface tension constraints at microscales. Our findings defy this paradigm by demonstrating that cicadas-weighing just 2 g-possess the capability for jetting fluids through remarkably small orifices. Using dimensional analysis, we introduce a unifying fluid dynamics scaling framework that accommodates a broad range of taxa, from surface-tension-dominated insects to inertia and gravity-reliant mammals...

Recent electronics-tissues biointefacing technology has offered unprecedented opportunities for long-term disease diagnosis and treatment. It remains a grand challenge to robustly anchor the pressure sensing bioelectronics onto specific organs, since the periodically-varying stress generated by normal biological processes may pose high risk of interfacial failures. Here, we report a general yet reliable approach to achieve the robust hydrogel interface between wireless pressure sensor and biological tissues/organs, featuring highly desirable mechanical compliance and swelling resistance, despite the direct contact with biofluids and dynamic conditions...

We developed fluorescent protein sensors for nicotine with improved sensitivity. For iNicSnFR12 at pH 7.4, the proportionality constant for ∆F/F0 vs [nicotine] (δ-slope, 2.7 μM-1) is 6.1-fold higher than the previously reported iNicSnFR3a. The activated state of iNicSnFR12 has a fluorescence quantum yield of at least 0.6. We measured similar dose-response relations for the nicotine-induced absorbance increase and fluorescence increase, suggesting that the absorbance increase leads to the fluorescence increase via the previously described nicotine-induced conformational change, the "candle snuffer" mechanism...

The analysis of structures in dried droplets has made it possible to detect the presence and conformational state of macromolecules in relevant biofluids. Therefore, the implementation of novel drying strategies for pattern formation could facilitate the identification of biomarkers for the diagnosis of pathologies. We present an experimental study of patterns formed by evaporating water-diluted blood droplets on a vertical surface. Three significant morphological features were observed in vertical droplet deposits: (1) The highest concentration of non-volatile molecules is consistently deposited in the lower part of the droplet, regardless of erythrocyte concentration...

The direct and unambiguous detection and identification of individual metabolite molecules present in complex biological mixtures constitute a major challenge in (bio)analytical research. In this context, nuclear magnetic resonance (NMR) spectroscopy has proven to be particularly powerful owing to its ability to provide both qualitative and quantitative atomic-level information on multiple analytes simultaneously in a noninvasive manner. Nevertheless, NMR suffers from a low inherent sensitivity and, moreover, lacks selectivity regarding the number of individual analytes to be studied in a mixture of a myriad of structurally and chemically very different molecules, e...

Our study aims to provide basic insights on the impact of the spiral shape of the cochlea, i.e., of geometric torsion and curvature, on wall pressure and wall shear stress. We employed computational fluid dynamics in square duct models with curvature and torsion similar to those found in human cochleae. The results include wall pressures and wall shear stresses within the ducts under oscillating axial flow. Our findings indicate that the helical shape generates higher transverse wall shear stresses compared to exclusively curved or twisted ducts...

Glioblastoma (GB) tumors are one of the most insidious cancers which take over the brain and defy therapy. Over time and in response to treatment the tumor and the brain cells in the tumor microenvironment (TME) undergo many genetic/epigenetic driven changes in their phenotypes and this is reflected in the cellular contents within the extracellular vesicles (EVs) they produce. With the result that some EVs try to subdue the tumor (friends of the brain), while others participate in the glioblastoma takeover (foes of the brain) in a dynamic and ever changing process...

Blood testing has traditionally been the gold standard for the physiological analysis and monitoring of professional athletes. In recent years, blood testing has moved out of the laboratory thanks to portable handheld devices, such as lactate meters. However, despite its usefulness and widespread use, blood testing has several drawbacks and limitations, such as the need for the athlete to stop exercising for blood extraction and the inability to have data continuously collected. In this scenario, sweat has become an alternative to blood testing because of its rich content of electrolytes and metabolites, as well as small quantities of sugars, proteins, and ions...

The separation of rare cells from complex biofluids has attracted attention in biological research and clinical applications, especially for cancer detection and treatment. In particular, various technologies and methods have been developed for the isolation of circulating tumor cells (CTCs) in the blood. Among them, the induced-charge electrokinetic (ICEK) flow method has shown its high efficacy for cell manipulation where micro-vortices (MVs), generated as a result of induced charges on a polarizable surface, can effectively manipulate particles and cells in complex fluids...

Probiotics are live microorganisms that confer health benefits when administered in adequate amounts. They are used to promote gut health and alleviate various disorders. Recently, there has been an increasing interest in the potential effects of probiotics on human physiology. In the presented study, the effects of probiotic treatment on the metabolic profiles of human urine and serum using a nuclear magnetic resonance (NMR)-based metabonomic approach were investigated. Twenty-one healthy volunteers were enrolled in the study, and they received two different dosages of probiotics for 8 weeks...

In recent years, magnetoactive soft continuum robots (MSCRs) with multimodal locomotion capabilities have emerged for various biomedical applications. Developments in nonlinear dynamic models and effective control methods for MSCRs are deemed vital not only to gain a better understanding of their coupled magneto-mechanical behavior but also to accurately steer the MSCRs inside the human body. This study presents a novel dynamic model and model-based AI-driven control method to guide an MSCR in a fluidic environment...

Portable sample-to-answer devices with applications in point-of-care settings have emerged to obviate the necessity of centralized laboratories for biomarker analysis. In this work, a smartphone-operated and additively manufactured multiplexed electrochemical device (AMMED) is presented for the portable detection of biomarkers in blood and saliva. AMMED is comprised of a customized portable potentiostat with a multiplexing feature, a 3D-printed sample collection cartridge to handle three samples of saliva and blood at the same time, a smartphone application to remotely control the potentiostat, and a 3D-printed-based multiplexed microfluidic electrochemical biosensor (test chip)...

Female fertility decreases during aging. The development of effective therapeutic strategies to address the age-related decline in oocyte quality and quantity and its accurate diagnosis remain major challenges. In this review, we summarize our current understanding of the study of aging and infertility, focusing primarily on the molecular basis of energy metabolism, mitochondrial function, and redox homeostasis in granulosa cells and oocytes, and discuss perspectives on future research directions. Mitochondria serve as a central hub sensing a multitude of physiological processes, including energy production, cellular redox homeostasis, aging, and senescence...

Cerebrospinal fluid (CSF) is a metabolically diverse biofluid and a key specimen for exploring biochemical changes in neurodegenerative diseases. Detecting lipid species in CSF using mass spectrometry (MS)-based techniques remains challenging because lipids are highly complex in structure, and their concentrations span over a broad dynamic range. This work aimed to develop a robust lipidomics and metabolomics method based on commonly used two-phase extraction systems from human CSF samples. Prioritizing lipid detection, biphasic extraction methods, Folch, Bligh and Dyer (B&D), Matyash, and acidified Folch and B&D (aFolch and aB&D) were compared using 150 μL of human CSF samples for the simultaneous extraction of lipids and metabolites with a wide range of polarity...

Parkinson's disease (PD) is a widespread neurodegenerative disorder, whose complex aetiology remains under construction. While rare variants have been associated with the monogenic PD form, most PD cases are influenced by multiple genetic and environmental aspects. Nonetheless, the pathophysiological pathways and molecular networks involved in monogenic/idiopathic PD overlap, and genetic variants are decisive in elucidating the convergent underlying mechanisms of PD. In this scenario, metabolomics has furnished a dynamic and systematic picture of the synergy between the genetic background and environmental influences that impact PD, making it a valuable tool for investigating PD-related metabolic dysfunctions...

The misuse of cannabinoids and their synthetic variants poses significant threats to public health, necessitating the development of advanced techniques for detection of these compounds in biological or environmental samples. Existing methods face challenges like lengthy sample pretreatment and laborious antifouling steps. Herein, we present a novel sensing platform using magnetic nanorods coated with zwitterionic polymers for the simple, rapid, and sensitive detection of cannabinoids in biofluids. Our technique utilizes the engineered derivatives of the plant hormone receptor Pyrabactin Resistance 1 (PYR1) as drug recognition elements and employs the chemical-induced dimerization (CID) mechanism for signal development...