Concentration Ratio Research Articles

A sustainable HPTLC approach for green assessment of Tyrosine to phenylalanine ratio in chronic kidney disease

AbstractThe kidney is considered the main site for the net release of Tyrosine (Tyr) to the circulation through hydroxylation of Phenylalanine (Phe) using phenylalanine hydroxylase enzyme. In chronic kidney disease (CKD) patients the enzyme activity is impaired, therefore the serum concentration ratio of Tyr/Phe is reduced compared to healthy individuals. This motivates us to develop a cost effective, green, simple, sensitive, and selective HPTLC method to measure the levels of Tyr and Phe in serum samples. The analysis was carried out using acetonitrile: ethanol: 25% ammonia solution: ethyl acetate (6.5: 1.5: 1: 0.5) as a mobile phase. Rf values were 0.55 ± 0.05 for Phe and 0.39 ± 0.05 for Tyr. Densitometry scanning was performed using UV detector and dual wavelengths of 210 and 225 nm were obtained. A linear correlation was observed between the levels of Phe and Tyr, ranging from 50 to 700 ng band− 1 and 50 to 600 ng band− 1, respectively, under the optimum conditions. The method selectivity, linearity, precision, accuracy, and robustness were all confirmed in accordance with ICH recommendations. Calculations of the separation and resolution factors, number of theoretical plates, and height equivalent to theoretical plates prove to the chromatographic system accuracy and high separation efficiency. The developed method exhibits an acceptable eco-scale when measuring the method greenness using AGREE and GAPI softwares. It was applied for the determination of Phe and Tyr concentrations in human serum samples.

Workability of Nanomodified Self-Compacting Geopolymer Concrete Based on Response Surface Method

Geopolymer concrete is more low-carbon and environmentally friendly than Portland cement concrete. Nanoparticle modification can help to improve the mechanical and durability performance of concrete, but due to its large specific surface area and high activity, it may deteriorate its workability. However, there is currently limited research on the effect of nanomodification on the workability of freshly mixed self-compacting geopolymer concrete (SCGC). This article conducted SCGC workability experiments using the response surface methodology, which included 29 different mixtures. The effects of nano-silica (NS), nano-calcium carbonate (NC), alkali content (N/B), and water cement ratio (W/B) on the workability of SCGC were studied. The experimental results show that the addition of NS and NC can reduce the slump expansion of SCGC, and the combination of the two significantly increases the amplitude of slump expansion with the change in nanomaterial content. An increase in N/B will reduce the expansion time and clearance value of SCGC. As N/B increases from 4% to 4.4%, the slump extension of SCGC decreases, and with a further increase in N/B, the slump extension increases significantly to 68.1 cm, which means that the slump extension of SCGC increases by 9.5% as N/B increases from 4.4 to 5. This study can provide a reference for optimizing the fresh performance of geopolymer concrete and improving the mechanism of nanomaterial-modified geopolymer concrete.

Computational Model-Assisted Development of a Nonenzymatic Fluorescent Glucose-Sensing Assay.

Deep-red fluorescence was implemented in this fully injectable, nonenzymatic glucose biosensor design to allow for better light penetration through the skin, particularly for darker skin tones. In this work, a novel method was developed to synthesize Cy5.5 labeled mannose conjugates (Cy5.5-mannobiose, Cy5.5-mannotriose, and Cy5.5-mannotetraose) to act as the fluorescent competing ligand in a competitive binding assay with the protein Concanavalin A acting as the recognition molecule. Using fluorescence anisotropy (FA) data, a computational model was developed to determine optimal concentration ratios of the assay components to allow for sensitive glucose measurements within the physiological range. The model was experimentally validated by measuring the glucose response via FA of the three Cy5.5-labeled mannose conjugates synthesized with Cy5.5-mannotetraose demonstrating the most sensitive response to glucose across the physiological range. The developed method may be broadly applied to a vast range of commercially available fluorescent dyes and opens up opportunities for glucose measurements using nonenzymatic assays.

DFT-Guided Design of Dual Dopants in Anatase TiO2 for Boosted Sodium Storage.

Anatase titanium dioxide (TiO2) has drawn great attention as an anode material in sodium ion batteries (SIBs), but it suffers from the sluggish diffusion kinetics of Na+ within TiO2 and inferior electronic conductivity. Herein, under the guidance of density functional theory (DFT), we propose a nitrogen and selenium dual-doped TiO2 system as an advanced SIB anode. Both DFT and experimental investigations reveal the cooperative effect of dopants in boosting the electrochemical performance of TiO2, finding the optimal content ratio (N/Se at 1:3) for overall improved SIB performances. As expected, experimental results exhibit excellent sodium storage behavior of the N,Se-doped TiO2, including high discharge capacity (142 mAh g-1 at 2 A g-1), good rate performance (82 mAh g-1 at 20 A g-1), and ultralong cyclability (97% retention over 5000 cycles at 2 A g-1). Our study underscores the importance of dual-heteroatom doping in the rational design of advanced electrode materials.

Long short term memory networks for predicting resilient Modulus of stabilized base material subject to wet-dry cycles.

The resilient modulus (MR) of different pavement materials is one of the most important input parameters for the mechanistic-empirical pavement design approach. The dynamic triaxial test is the most often used method for evaluating the MR, although it is expensive, time-consuming, and requires specialized lab facilities. The purpose of this study is to establish a new model based on Long Short-Term Memory (LSTM) networks for predicting the MR of stabilized base materials with various additives during wet-dry cycles (WDC). A laboratory dataset of 704 records has been used using input parameters, including WDC, ratio of calcium oxide to silica, alumina, and ferric oxide compound, Maximum dry density to the optimal moisture content ratio (DMR), deviator stress (σd), and confining stress (σ3). The results demonstrate that the LSTM technique is very accurate, with coefficients of determination of 0.995 and 0.980 for the training and testing datasets, respectively. The LSTM model outperforms other developed models, such as support vector regression and least squares approaches, in the literature. A sensitivity analysis study has determined that the DMR parameter is the most significant factor, while the σd parameter is the least significant factor in predicting the MR of the stabilized base material under WDC. Furthermore, the SHapley Additive exPlanations approach is employed to elucidate the optimal model and examine the impact of its features on the final result.

Generating Tooth Organoids Using Defined Bioorthogonally Cross-Linked Hydrogels.

Generating teeth in vitro requires mimicking tooth developmental processes. Biomaterials are essential to support 3D tooth organoid formation, but their properties must be finely tuned to achieve the required biomimicry for tooth development. For the first time, we used bioorthogonally cross-linked hydrogels as defined 3D matrixes for tooth developmental engineering, and we highlighted how their properties play a pivotal role in enabling 3D tooth organoid formation in vitro. We prepared hydrogels by mixing gelatin precursors modified either with tetrazine (Tz) or norbornene (Nb) moieties. We tuned the hydrogel properties (E = 2-7 kPa; G' = 500-1500 Pa) by varying the gelatin concentration (8% vs 12% w/V) and stoichiometric ratio (Tz:Nb = 1 vs 0.5). We encapsulated dental epithelial-mesenchymal cell pellets in a library of hydrogels and identified a hydrogel formulation that enabled successful growth kinetics and morphogenesis of tooth germs, introducing a defined tunable platform for tooth organoid engineering and modeling.

Study of the rheological properties and nautical depth assessment of fine sediments in Iranian ports

Sediments containing more than 10% clay particles by mass can exhibit cohesive properties. Cohesive sediments are commonly found in coastal areas worldwide, including the southern shore of the Caspian Sea and the northern/northwestern beaches of the Persian Gulf. These cohesive sediments can form a layer of soft to extremely soft mud, known as fluid mud, covering the seabed. The study examined the properties of natural mud samples collected from different depths and locations within three Iranian ports: Anzali Port (Caspian Sea), and Khorramshahr and Bushehr Ports (Persian Gulf). The laboratory analyses included determining the sediment grain-size distribution, density, carbonate content, organic matter content, and rheological properties at different water content ratios. Disregarding the impact of variations in organic matter and carbonate contents in the samples, water content ratio was the main factor affecting the rheological properties of sediments.

CTNI-29. A PHASE 1B STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS, AND OBJECTIVE RESPONSE OF LP-184 ALONE AND IN COMBINATION WITH SPIRONOLACTONE IN IDH WILD TYPE GLIOBLASTOMA AT FIRST PROGRESSION

Abstract LP-184 is a fully synthetic small molecule alkylator of the acylfulvene therapeutics class that induces DNA double-strand breaks and improves survival in orthotopic GBM xenograft models. In preclinical studies, LP-184 is brain penetrant with a brain tumor/plasma concentration ratio of 0.2. DNA damage induced by acylfulvenes is repaired via transcription-coupled nucleotide excision repair (TC-NER) mediated by ERCC complexes. GBM with intrinsic or pharmacologically induced DNA Damage Repair deficiency (dDDR) may preferentially respond to LP-184, independent of MGMT status. LP-184 is currently under investigation in a first-in-human Phase 1a dose-escalation safety study (NCT05933265) in adult patients with advanced solid tumors including GBM, with no dose-limiting toxicities to date at dose level 6. Following determination of the Maximum Tolerated Dose and/or Recommended Phase 2 Dose from Phase 1a, the selected expansion dose will be assessed in a Phase 1b study to evaluate the safety, pharmacokinetics, and objective response of LP-184 alone and in combination with spironolactone in IDH wild type glioblastoma at first progression. Spironolactone is a brain penetrant FDA approved agent that proteolytically degrades the TC-NER component ERCC3, thereby creating dDDR. Two rGBM cohorts will be enrolled according to a Simon’s 2-stage optimal design: (i) LP-184 alone (days 1 and 8 in a 21-day cycle, as intravenous infusion over 30 minutes) and (ii) combination of LP-184 and spironolactone (200 mg orally daily in conjunction and before the LP-184 infusion). In the first stage, 10 response evaluable subjects will be enrolled. If 1 or more of the first 10 response evaluable subjects achieve an objective response, 19 further subjects may be accrued in the second stage. In each cohort, at least 5 subjects will undergo planned tumor resection and will be treated with LP-184 or the combination the day prior to surgery to evaluate PK/PD.

SILVER NANOPARTICLES-AQUEOUS LEAF EXTRACT OF SIDAGURI (SIDA RHOMBIFOLIA) AS REDUCING AGENTS

The Sidaguri leaf, scientifically known as Sida rhombifolia, is a plant species rich in flavonoids that have the ability to act as reducing agent in formation of silver nanoparticles. This study presented the synthesis of silver nanoparticles (AgNp-Sid) using aqueous leaf extract of sidaguri. This study utilized a concentration ratio of 2:90 mL aqueous leaf extract of Sidaguri and AgNO3 1 mM. The size and morphology of AgNp-Sid was measured using UV-Visible Spectrophotometer, PSA, FT-IR, SEM-EDS, and XRD. The investigation revealed an ordinary particle size of 63.5 nm with polydispersity index (PI) of 0.284. The maximum wavelength varies between 405.4 nm and 407.8 nm with the increasing of time. AgNp-Sid exhibited a spherical morphology and had a crystalline structure that is face-centered cubic. The results suggested that the aqueous leaf extract of sidaguri had the ability to function as a reducing agent in the synthesis of silver nanoparticles, offering a safe, cost-effective, and environmentally friendly alternative.

Combining Electrochemical Nitrate Reduction and Anammox for Treatment of Wastewater With Low C/N Ratio Nitrate

ABSTRACTThe treatment of high concentration and low C/N ratio of nitrate wastewater is a promising and challenging research topic. Combining electrochemical reduction and anammox is a technology with great development potential for nitrogen removal from wastewater. In this work, Cu─Ag─Co cathode materials were prepared by two‐step electrodeposition method. The effect of current density and initial pH value on nitrate reduction efficiency was investigated in a single chamber electrolytic cell equipped with Cu─Ag─Co cathode and Ti/RuO2─IrO2 anode. The results showed that under the conditions of initial NO3−─N concentration of 500 mg L−1, Na2SO4 concentration of 0.125 mol L−1, current density of 10 mA cm−2, initial pH value of 7, and treatment time of 5 h, NO3−─N removal ratio was 84.5%, the concentration of NO2−─N and NH4+─N was 180.2 mg L−1 and 173.2 mg L−1. Wastewater with a concentration ratio of NO2−─N and NH4+─N of 1.04:1 meets the influent requirements for anaerobic ammonia oxidation. Through the combination process, the final NO3−─N removal ratio was 82.6%, the NO2−─N concentration was 3.2 mg L−1, and the NH4+─N concentration was 26.4 mg L−1. It provided a reference for the treatment of wastewater with low C/N ratio nitrate by combining electrochemical reduction and anammox.

Liver cyst penetration of antibiotics at the target site of infection: a randomized pharmacokinetic trial.

The EASL cystic liver disease guideline states that drug penetration at the site of infection (liver cyst) is essential for successful treatment, but pharmacokinetic (PK) data on cyst penetration are limited. This study aims to investigate tissue penetration of four antibiotics in non-infected liver cysts and explores influencing factors. We performed a prospective, randomized single-dose PK-study. Before percutaneous drainage of a non-infected liver cyst, an intravenous (IV) dose of either ciprofloxacin and piperacillin/tazobactam (group 1); or co-trimoxazole (trimethoprim/sulfamethoxazole) and doxycycline (group 2) was given. Cyst fluid was collected during drainage. Blood samples were obtained before, during and after drainage (within 12 h). Drug concentrations were measured with a validated LC-MS/MS. Primary outcome was liver cyst penetration, defined as the cyst-fluid-to-plasma concentration ratio (%) expressed as median (IQR). We included 20 patients, and 21 liver cysts were drained (group 1: n = 11, group 2: n = 10). Median drained cyst volume was 700 mL. Median time between infusion and drainage was 139 min (IQR 120-188 min). Median cyst-fluid-to-plasma concentration ratio was 4.2% (IQR 1.6%-8.9%) for ciprofloxacin, 0.3% (IQR 0.0%-1.3%) for piperacillin, 0.2% (IQR 0.0%-1.3%) for tazobactam, 12.2% (IQR 6.3%-16.1%) for trimethoprim, 0.4% (IQR 0.2%-3.8%) for sulfamethoxazole and 1.6% (IQR 0.9%-2.3%) for doxycycline. Time between trimethoprim infusion and cyst drainage was correlated with increased cyst-fluid-to-plasma concentration ratio (P < 0.01). Trimethoprim and ciprofloxacin have the highest penetration ratios amongst antibiotics tested. We found that liver cyst penetration varies widely between drugs after a single IV dose. NTR8499The trial was originally registered in the Netherlands Trial Register (ID: NL7290), which was converted to the International Clinical Trials Registry Platform in 2022.

Comparative Dissolution Study of Ciprofloxacin Hydrochloride-sustained Release Tablets by Using Carbopol-934 and Guar Gum Polymers

Aims: This study aimed to identify the potential release of the drug from the tablet dosage form using Carbopol-934 and Guar Gum polymers at different concentration ratios. Objective: The objective of this study was to determine the cumulative percentage of ciprofloxacin hydrochloride released from different polymers. Method: We formulated ciprofloxacin hydrochloride sustained-release tablets with Carbopol-934 and Guar gum using the wet granulation method. For the formulation of sustained-release ciprofloxacin hydrochloride tablets, both polymers were mixed in varying ratios. The tablets were examined for pre-formulation studies, including the angle of repose, bulk density, compressibility index, and physiological properties, such as variations in weight, friability, and drug content. For postformulation studies, such as the in vitro study, the in vitro release of the drugs was evaluated in a phosphate buffer solution (pH 7.4) for 8 h. However, the physiological properties of ciprofloxacin hydrochloride tablets were limited due to their liberality. Results: The tablets containing guar gum (Batches B-I and B-II) showed better drug content than other polymer-based batches, such as Carbopol-934 (Batch A-I, A-II) and a mixture of both polymer Carbopol-934 and Guar gum (Batch C-I, C-II). Sustained drug release was observed in the guar gum polymer-based tablets (Batch B-II). It was observed that the dissolution profile of ciprofloxacin hydrochloride tablets formed using different polymers showed an increase in the polymer ratio, which can be related to the increase in drug release. Conclusion: From this study, we can conclude that the ciprofloxacin hydrochloride drug release percentage was maximum when guar gum polymer was used in the tablet dosage form.

Study on the Effect of n-Hexane Insolubles on Pyrolysis Product Yields Based on Statistical Regression Analysis

Pyrolysis technology has attracted much attention due to its efficient biomass conversion capability, but the significant impact of n-hexane insoluble matter (INS) concentration on pyrolysis product yield has not been fully studied. Therefore, it is of great significance to explore the impact of INS on the yields of tar, water and coke residue. This study developed a linear regression model to analyze the effect of INS concentration on these pyrolysis products. The results show that INS concentration has a significant positive impact on tar yield, but has a smaller impact on water and coke residue yields. In addition, this study constructed a generalized linear model (GLM) to examine the interaction between INS concentration and mixing ratio, and found that the interaction effect was not significant. These findings provide valuable insights into optimizing the co-pyrolysis process of biomass and coal, helping to improve energy conversion efficiency and reduce environmental impact.

Unlocking renewable fuel: Charcoal briquettes production from agro-industrial waste with cassava industrial binders

Increasing global fuel demand has created challenges in sourcing raw materials, making agro-waste biomass utilization for energy production a critical alternative. Therefore, the aim of this study was to investigate the production of charcoal briquettes using different base materials such as coconut shells (TC1), Leucaena leucocephala wood (TC2), and assorted wood charcoal residues (TC3), along with binders derived from cassava industry by-products—namely, tapioca starch (TB1), cassava peel (TB2), and cassava tubers (TB3) at binder content (BC) ratios of 5, 10, 15, and 20 by volume. Initially, assessing the physical properties, including proximate and ultimate analyses, was crucial for predicting effective charcoal production. The TC2 briquettes, using TB2 and TB3 binders at a BC20 concentration, were found to be optimal, displaying a high production capacity and low specific energy consumption. Using cassava peel and tubers as binders not only efficiently uses agricultural by-products, thereby reducing costs and avoiding competition with food resources (TC1) but also results in high-quality briquettes. In scenarios of raw material shortages, TC3 and TC2 can effectively replace TC1. Mechanically, TC3 and TC2 briquettes exhibited superior characteristics. Although BC20 enhances the mechanical properties and facilitates handling, it may compromise heat release. Thermally, a higher BC decreases the charcoal proportion, leading to increased ignition time, reduced calorific value, and heating effectiveness. In conclusion, the successful production of charcoal briquettes from agro-industrial waste using cassava industrial binders presents a viable pathway towards more sustainable energy practices, improves waste management, and adds value to agricultural waste.

Electrochemical Characteristics of Ambarella Peel Waste as Liquid Electrolyte for Zn-Cu Biobattery

This study focuses on the electrochemical characterization of Zn-Cu bio-battery cells utilizing electrolytes derived from ambarella peel waste. The primary objectives are to determine the half-cell and full-cell characteristics of these bio-batteries at various concentration ratios and to identify the optimal concentration ratio for maximum performance. Cyclic voltammetry analysis of the half-cells revealed an oxidation peak at 0.5 V vs Ag/AgCl, corresponding to the conversion of uronic acid to aldaric acid. Additionally, two reduction peaks were observed: hydrogen ion reduction to H2 at 0 V vs Ag/AgCl and water reduction at –0.42 V vs Ag/AgCl. The rate-determining step analysis indicated that the redox reactions in the ambarella peel electrolyte solution were surface reactions. The highest rate constant (ks) of 0.722 ± 0.05 s–1 was observed at a 1:2 concentration ratio. This ratio also resulted in the highest battery capacity of 0.0816 mAh and the maximum power density of 16.13 mW/m2. The study concluded that the 1:2 concentration ratio of ambarella peel waste electrolyte solution is optimal, outperforming the 1:1 and 1:3 ratios in terms of battery capacity and power density.

Analysis of Optical Window for Constant Cooling Heat Flux‐Based Spectral Splitting in Concentrator Photovoltaic System

The solar cells cooled to constant temperature at different concentration ratios (CR) and spectral bands (SB) require the same cooling heat flux (CHF), but the output power varies significantly. Thus, it is necessary to clarify the relationship of CHF‐CR‐SB to provide a reference for photovoltaic systems to select the output power generation of the spectral band under constant cooling heat flux. In this article, a selecting spectra model of a centralized photovoltaic (CPV) system is established and the selection of the spectrum based on CHF and the CR is analyzed. Theory shows that the wider the spectral division of the same CR, the larger the cooling heat flux consumed. The narrower the spectrum division, the higher the CR that the cell receiver can withstand. The experiments show that the higher the photoelectric conversion efficiency (PCE), the lower the cooling heat flux to be consumed. The cooling heat flux of 650 filter consumes 22.74% more than the UV700 filter, which means the demand for CHF is more severe when the heat spectrum distribution is wide. The spectral division should be carried out according to the requirements of high‐energy flux but a small thermal energy proportion to achieve efficient PCE.

Advanced nano-composite coatings of ZrB₂/ZrC/SiC on carbon fibers via eco-friendly precursor synthesis

This study presents a comprehensive investigation into the synthesis and characterization of ZrB2/ZrC/SiC composite coatings on carbon fiber substrates via a solution-based process followed by high-temperature pyrolysis. The precursor solution was prepared using Gum Ghatti (GG), zirconyl chloride, tetraethyl orthosilicate, and boric acid. Optimization of precursor concentration and molar ratios was performed to achieve suitable viscosity and composition. The pyrolysis process was conducted in an argon atmosphere, resulting in the formation of well-defined ZrB2, ZrC, and SiC phases. XRD analysis confirmed the phase composition, while SEM imaging revealed spheroidal particle aggregates with a uniform distribution of composite phases. TG-DTA analysis reveals the thermal decomposition behavior, highlighting distinct stages of mass loss and phase transformations. Coated carbon fibers exhibited enhanced oxidation resistance, as evidenced by TGA analysis. SEM analysis confirmed the uniform distribution and adhesion of the composite matrix on the carbon fiber substrate. This study demonstrates the successful synthesis of ZrB2/ZrC/SiC composite coatings with promising thermal properties for advanced applications.

Formulation-dependent differences in paclitaxel distribution to anatomical sites relevant to chemotherapy-induced peripheral neuropathy

IntroductionChemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting adverse event observed in patients receiving paclitaxel, associated with initial pathological changes in the peripheral nervous system, i.e., distal nerves and dorsal root ganglia (DRG). The prevalence of CIPN in patients receiving paclitaxel formulated i) in polyethylated castor oil with ethanol (CreEL-PTX), ii) as albumin-bound (nab-PTX), and iii) in XR17 micelles (micellar-PTX), is unexpectedly varying. We hypothesize that the discrepancy in CIPN prevalence could be governed by differences in the extent of paclitaxel distribution across blood-to-tissue barriers at the CIPN-sites, caused by the specific formulation.MethodsThe recently developed Combinatory Mapping Approach for CIPN was used to determine the unbound tissue-to-plasma concentration ratio Kp,uu,tissue, after a 4-h infusion of 4 mg/kg CreEL-PTX, 4 mg/kg nab-PTX or 1 mg/kg micellar-PTX in male and female Sprague Dawley rats. Kp,uu,tissue was determined in conventional (DRG, sciatic nerve) and non-conventional (brain, spinal cord, skeletal muscle) CIPN-sites.ResultsBased on our data, the Cremophor-free paclitaxel formulations were associated with a higher distribution of paclitaxel to CIPN-sites than CreEL-PTX, e.g., Kp,uu,DRG of 0.70 and 0.60 for nab-PTX and micellar-PTX, respectively, in comparison to 0.27 for CreEL-PTX (p &amp;lt; 0.01). In addition, the fraction of unbound paclitaxel in plasma was on average 1.6-fold higher in nab- and micellar PTX arms and equal to 0.061 and 0.065, respectively, compared to 0.039 for the CreEL-PTX treatment arm (p &amp;lt; 0.0001).DiscussionIn the case of similar unbound paclitaxel concentration in the plasma of patients and assumed species-independent extent of paclitaxel transport across the barriers, nab- and micellar-PTX formulations can lead to higher paclitaxel exposure at CIPN-sites in comparison to CreEL-PTX.

Deep Learning-Assisted Label-Free Parallel Cell Sorting with Digital Microfluidics.

Sorting specific cells from heterogeneous samples is important for research and clinical applications. In this work, a novel label-free cell sorting method is presented that integrates deep learning image recognition with microfluidic manipulation to differentiate cells based on morphology. Using an Active-Matrix Digital Microfluidics (AM-DMF) platform, the YOLOv8 object detection model ensures precise droplet classification, and the Safe Interval Path Planning algorithm manages multi-target, collision-free droplet path planning. Simulations and experiments revealed that detection model precision, concentration ratios, and sorting cycles significantly affect recovery rates and purity. With HeLa cells and polystyrene beads as samples, the method achieved 98.5% sorting precision, 96.49% purity, and an 80% recovery over three cycles. After a series of experimental validations, this method can also be used to sort HeLa cells from red blood cells, cancer cells from white blood cells (represented by HeLa and Jurkat cells), and differentiate white blood cell subtypes (represented by HL-60 cells and Jurkat cells). Cells sorted using this method can be lysed directly on chip within their hosting droplets, ensuring minimal sample loss and suitability for downstream bioanalysis. This innovative AM-DMF cell sorting technique holds significant potential to advance diagnostics, therapeutics, and fundamental research in cell biology.

Evaluating in vivo data for drug metabolism and transport: lessons from Kirchhoff’s Laws

Mechanistic models of hepatic clearance have been evaluated for more than 50 years, with the first author of this mini-review serving as a co-author of the first paper proposing such a model. However, published quality experimental data are only consistent with the first of these models, designated as the well-stirred model, despite the universal recognition that this model is physiologically unrepresentative of what occurs with respect to liver metabolism and transport. Within the last 3 years, our laboratory has recognized that it is possible to derive clearance equations employing the concepts of Kirchhoff’s Laws from physics, independent of the differential equation approach that has been utilized to derive reaction rates in chemistry. Here we review our published studies showing that the equation previously believed to be the well-stirred model, when hepatic basolateral transporters are not clinically relevant, is in fact the general equation for hepatic clearance when only systemic drug concentrations are measured, explaining why all experimental data fit this equation. To demonstrate that the equations deriving the mechanistic models of hepatic elimination for the past 50 years are not valid, we show that when calculating Kpuu, the ratio of unbound drug concentration in the liver to the unbound concentration of drug in the systemic circulation, for the well-stirred, parallel tube and dispersion models, Kpuu surprisingly can never exceed 1 and is a function of FH, the hepatic bioavailability following oral dosing. We believe that knowledgeable drug metabolism scientist and clinical pharmacologist will agree that this outcome is nonsensical.