Two-component macrophage model for active phagocytosis with pseudopod formation.

Macrophage phagocytosis is critical for the immune response, homeostasis regulation, and tissue repair. This intricate process involves complex changes in cell morphology, cytoskeletal reorganization, and various receptor-ligand interactions controlled by mechanical constraints. However, there is a lack of comprehensive theoretical and computational models that investigate the mechanical process of phagocytosis in the context of cytoskeletal rearrangement. To address this issue, we propose a novel coarse-grained mesoscopic model that integrates a fluid-like cell membrane and a cytoskeletal network to study the dynamic phagocytosis process. The growth of actin filaments results in the formation of long and thin pseudopods, and the initial cytoskeleton can be disassembled upon target entry and reconstructed after phagocytosis. Through dynamic changes in the cytoskeleton, our macrophage model achieves active phagocytosis by forming a phagocytic cup utilizing pseudopods in two distinct ways. We have developed a new algorithm for modifying membrane area to prevent membrane rupture and ensure sufficient surface area during phagocytosis. In addition, the bending modulus, shear stiffness, and cortical tension of the macrophage model are investigated through computation of the axial force for the tubular structure and micropipette aspiration. With this model, we simulate active phagocytosis at the cytoskeletal level and investigate the mechanical process during the dynamic interplay between macrophage and target particles.

Elaborating the Crystal Water of Prussian Blue for Outstanding Performance of Sodium Ion Batteries.

Prussian blue (PB) is one of the main cathode materials with industrial prospects for the sodium ion battery. The structural stability of PB materials is directly associated with the presence of crystal water within the open 3D framework. However, there remains a lack of consensus regarding whether all forms of crystal water have detrimental effects on the structural stability of the PB materials. Currently, it is widely accepted that interstitial water is the stability troublemaker, whereas the role of coordination water remains elusive. In this work, the dynamic evolution of PB structures is investigated during the crystal water (in all forms) removal process through a variety of online monitoring techniques. It can be inferred that the PB-130 °C retains trace coordination water (1.3%) and original structural integrity, whereas PB-180 °C eliminates almost all of crystal water (∼12.1%, including both interstitial and coordinated water), but inevitably suffers from structural collapse. This is mainly because the coordinated water within the PB material plays a crucial role in maintaining structural stability via forming the -N≡C-FeLS-C≡N- conjugate bridge. Consequently, PB-130 °C with trace coordination water delivers superior reversible capacity (113.6 mAh g-1), high rate capability (charge to >80% capacity in 3 min), and long cycling stability (only 0.012% fading per cycle), demonstrating its promising prospect in practical applications.

Generation of Multiple Concentration Gradients Using a Two-Dimensional Pyramid Array.

Concentration heterogeneity of diffusible reactants is a prevalent phenomenon in biochemical processes, requiring the generation of concentration gradients for the relevant experiments. In this study, we present a high-density pyramid array microfluidic network for the effective and precise generation of multiple concentration gradients. The complex gradient distribution in the 2D array can be adaptively adjusted by modulating the reactant velocities and concentrations at the inlets. In addition, the unique design of each reaction chamber and mixing block in the array ensures uniform concentrations within each chamber during dynamic changes, enabling large-scale reactions with low reactant volumes. Through detailed numerical simulation of mass transport within the complex microchannel networks, the proposed method allows researchers to determine the desired number of reaction chambers within a given concentration range based on experimental requirements and to quickly obtain the operating conditions with the help of machine learning-based prediction. The effectiveness in generating a multiple concentration gradient environment was further demonstrated by concentration-dependent calcium carbonate crystallization experiments. This device provides a highly efficient mixing and adaptable concentration platform that is well suited for high-throughput and multiplexed reactions.

A combined computational and experimental investigation of the filtration function of splenic macrophages in sickle cell disease.

Being the largest lymphatic organ in the body, the spleen also constantly controls the quality of red blood cells (RBCs) in circulation through its two major filtration components, namely interendothelial slits (IES) and red pulp macrophages. In contrast to the extensive studies in understanding the filtration function of IES, fewer works investigate how the splenic macrophages retain the aged and diseased RBCs, i.e., RBCs in sickle cell disease (SCD). Herein, we perform a computational study informed by companion experiments to quantify the dynamics of RBCs captured and retained by the macrophages. We first calibrate the parameters in the computational model based on microfluidic experimental measurements for sickle RBCs under normoxia and hypoxia, as those parameters are not available in the literature. Next, we quantify the impact of key factors expected to dictate the RBC retention by the macrophages in the spleen, namely, blood flow conditions, RBC aggregation, hematocrit, RBC morphology, and oxygen levels. Our simulation results show that hypoxic conditions could enhance the adhesion between the sickle RBCs and macrophages. This, in turn, increases the retention of RBCs by as much as four-fold, which could be a possible cause of RBC congestion in the spleen of patients with SCD. Our study on the impact of RBC aggregation illustrates a 'clustering effect', where multiple RBCs in one aggregate can make contact and adhere to the macrophages, leading to a higher retention rate than that resulting from RBC-macrophage pair interactions. Our simulations of sickle RBCs flowing past macrophages for a range of blood flow velocities indicate that the increased blood velocity could quickly attenuate the function of the red pulp macrophages on detaining aged or diseased RBCs, thereby providing a possible rationale for the slow blood flow in the open circulation of the spleen. Furthermore, we quantify the impact of RBC morphology on their tendency to be retained by the macrophages. We find that the sickle and granular-shaped RBCs are more likely to be filtered by macrophages in the spleen. This finding is consistent with the observation of low percentages of these two forms of sickle RBCs in the blood smear of SCD patients. Taken together, our experimental and simulation results aid in our quantitative understanding of the function of splenic macrophages in retaining the diseased RBCs and provide an opportunity to combine such knowledge with the current knowledge of the interaction between IES and traversing RBCs to apprehend the complete filtration function of the spleen in SCD.

Single-cell characterization of deformation and dynamics of mesenchymal stem cells in microfluidic systems: A computational study.

Understanding the homing dynamics of individual mesenchymal stem cells (MSCs) in physiologically relevant microenvironments is crucial for improving the efficacy of MSC-based therapies for therapeutic and targeting purposes. This study investigates the passive homing behavior of individual MSCs in micropores that mimic interendothelial clefts through predictive computational simulations informed by previous microfluidic experiments. Initially, we quantified the size-dependent behavior of MSCs in micropores and elucidated the underlying mechanisms. Subsequently, we analyzed the shape deformation and traversal dynamics of each MSC. In addition, we conducted a systematic investigation to understand how the mechanical properties of MSCs impact their traversal process. We considered geometric and mechanical parameters, such as reduced cell volume, cell-to-nucleus diameter ratio, and cytoskeletal prestress states. Furthermore, we quantified the changes in the MSC traversal process and identified the quantitative limits in their response to variations in micropore length. Taken together, the computational results indicate the complex dynamic behavior of individual MSCs in the confined microflow. This finding offers an objective way to evaluate the homing ability of MSCs in an interendothelial-slit-like microenvironment.

Tapered Fiber Bioprobe Based on U-Shaped Fiber Transmission for Immunoassay.

In this paper, a tapered fiber bioprobe based on Mach-Zehnder interference (MZI) is proposed. To retain the highly sensitive straight-tapered fiber MZI sensing structure, we designed a U-shaped transmission fiber structure for the collection of optical sensing signals to achieve a miniature-insert-probe design. The spectrum responses from the conventional straight-tapered fiber MZI sensor and our proposed sensor were compared and analyzed, and experimental results showed that our proposed sensor not only has the same sensing capability as the straight-tapered fiber sensor, but also has the advantages of being flexible, convenient, and less liquid-consuming, which are attributed to the inserted probe design. The tapered fiber bioprobe obtained a sensitivity of 1611.27 nm/RIU in the refractive index detection range of 1.3326-1.3414. Finally, immunoassays for different concentrations of human immunoglobulin G were achieved with the tapered fiber bioprobe through surface functionalization, and the detection limit was 45 ng/mL. Our tapered fiber bioprobe has the insert-probe advantages of simpleness, convenience, and fast operation. Simultaneously, it is low-cost, highly sensitive, and has a low detection limit, which means it has potential applications in immunoassays and early medical diagnosis.

Impact of gravity on fluid flow and solute transport in the bone lacunar-canalicular system: a multiscale numerical simulation study.

Different gravity fields have important effects on the structural morphology of bone. The fluid flow caused by loadings in the bone lacunar-canalicular system (LCS), converts mechanical signals into biological signals and regulates bone reconstruction by affecting effector cells, which ensures the efficient transport of signaling molecules, nutrients, and waste products. In this study, the fluid flow and mass transfer effects of bone lacunar-canalicular system at multi-scale were firstly investigated, and a three-dimensional axisymmetric fluid-solid coupled finite element model of the LCS within three continuous osteocytes was established. The changes in fluid pressure field, flow velocity field, and fluid shear force variation on the surface of osteocytes within the LCS were studied comparatively under different gravitational fields (0 G, 1 G, 5 G), frequencies (1 Hz, 1.5 Hz, 2 Hz) and forms of cyclic compressive loading. The results showed that different frequencies represented different exercise intensities, suggesting that high-intensity exercise may accelerate the fluid flow rate within the LCS and enhance osteocytes activity. Hypergravity enhanced the transport of solute molecules, nutrients, and signaling molecules within the LCS. Conversely, the mass transfer in the LCS may be inhibited under microgravity, which may cause bone loss and eventually lead to the onset of osteoporosis. This investigation provides theoretical guidance for rehabilitative training against osteoporosis.

Ultra-sensitive all-optical phase modulation based on a fiber optic interferometer combined with Ti3C2Tx MXene-incorporated PDMS.

This study proposes an all-optical phase modulator based on a compact fiber optic interferometer combined with Ti3C2Tx MXene-incorporated PDMS. Due to the high photothermal conversion efficiency of MXene and the high thermo-optic coefficient of PDMS, changes in pump power can be effectively converted into refractive index (RI) variations in the PDMS. Then, by employing a fiber optic interferometer with a high RI response, ultra-sensitive all-optical phase modulation can be realized. The experimental results demonstrate that the resonant wavelength shift of the modulator with MXene-incorporated PDMS is 126 times higher than that of a modulator with single MXene deposition. Also, a maximum wavelength sensitivity of 14.57 nm/mW is achieved (equivalent to a phase sensitivity of 0.33π/mW); this excellent modulation performance is a great improvement on that of a previously reported fiber-based all-optical phase modulator. Furthermore, PDMS is also employed as a packaging layer to strengthen the device structure and restrict the heat in an enclosed space, which improves the heat utilization efficiency. The proposed device shows great potential in optical communication, optical filtering, sensing, and modulation applications.

A combined computational and experimental investigation of the filtration function of splenic macrophages in sickle cell disease.

Being the largest lymphatic organ in the body, the spleen also constantly controls the quality of red blood cells (RBCs) in circulation through its two major filtration components, namely interendothelial slits (IES) and red pulp macrophages. In contrast to the extensive studies in understanding the filtration function of IES, there are relatively fewer works on investigating how the splenic macrophages retain the aged and diseased RBCs, i.e., RBCs in sickle cell disease (SCD). Herein, we perform a computational study informed by companion experiments to quantify the dynamics of RBCs captured and retained by the macrophages. We first calibrate the parameters in the computational model based on microfluidic experimental measurements for sickle RBCs under normoxia and hypoxia, as those parameters are not available in the literature. Next, we quantify the impact of a set of key factors that are expected to dictate the RBC retention by the macrophages in the spleen, namely, blood flow conditions, RBC aggregation, hematocrit, RBC morphology, and oxygen levels. Our simulation results show that hypoxic conditions could enhance the adhesion between the sickle RBCs and macrophages. This, in turn, increases the retention of RBCs by as much as five-fold, which could be a possible cause of RBC congestion in the spleen of patients with SCD. Our study on the impact of RBC aggregation illustrates a 'clustering effect', where multiple RBCs in one aggregate can make contact and adhere to the macrophages, leading to a higher retention rate than that resulting from RBC-macrophage pair interactions. Our simulations of sickle RBCs flowing past macrophages for a range of blood flow velocities indicate that the increased blood velocity could quickly attenuate the function of the red pulp macrophages on detaining aged or diseased RBCs, thereby providing a possible rationale for the slow blood flow in the open circulation of the spleen. Furthermore, we quantify the impact of RBC morphology on their tendency to be retained by the macrophages. We find that the sickle and granular-shaped RBCs are more likely to be filtered by macrophages in the spleen. This finding is consistent with the observation of low percentages of these two forms of sickle RBCs in the blood smear of SCD patients. Taken together, our experimental and simulation results aid in our quantitative understanding of the function of splenic macrophages in retaining the diseased RBCs and provide an opportunity to combine such knowledge with the current knowledge of the interaction between IES and traversing RBCs to apprehend the complete filtration function of the spleen in SCD.

Circulating cellular clusters are associated with thrombotic complications and clinical outcomes in COVID-19.

We sought to study the role of circulating cellular clusters (CCC) -such as circulating leukocyte clusters (CLCs), platelet-leukocyte aggregates (PLA), and platelet-erythrocyte aggregates (PEA)- in the immunothrombotic state induced by COVID-19. Forty-six blood samples from 37 COVID-19 patients and 12 samples from healthy controls were analyzed with imaging flow cytometry. Patients with COVID-19 had significantly higher levels of PEAs (p value<0.001) and PLAs (p value = 0.015) compared to healthy controls. Among COVID-19 patients, CLCs were correlated with thrombotic complications (p value = 0.016), vasopressor need (p value = 0.033), acute kidney injury (p value = 0.027), and pneumonia (p value = 0.036), whereas PEAs were associated with positive bacterial cultures (p value = 0.033). In predictive in silico simulations, CLCs were more likely to result in microcirculatory obstruction at low flow velocities (≤1 mm/s) and at higher branching angles. Further studies on the cellular component of hyperinflammatory prothrombotic states may lead to the identification of novel biomarkers and drug targets for inflammation-related thrombosis.

Early and Sensitive Detection of Pathogens for Public Health and Biosafety: An Example of Surveillance and Genotyping of SARS-CoV-2 in Sewage Water by Cas12a-Facilitated Portable Plasmonic Biosensor.

Infectious diseases severely threaten public health and global biosafety. In addition to transmission through the air, pathogenic microorganisms have also been detected in environmental liquid samples, such as sewage water. Conventional biochemical detection methodologies are time-consuming and cost-ineffective, and their detection limits hinder early diagnosis. In the present study, ultrafine plasmonic fiber probes with a diameter of 125 µm are fabricated for clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas)-12a-mediated sensing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Single-stranded DNA exposed on the fiber surface is trans-cleaved by the Cas12a enzyme to release gold nanoparticles that are immobilized onto the fiber surface, causing a sharp reduction in the surface plasmon resonance (SPR) wavelength. The proposed fiber probe is virus-specific with the limit of detection of ~2,300 copies/ml, and genomic copy numbers can be reflected as shifts in wavelengths. A total of 21 sewage water samples have been examined, and the data obtained are consistent with those of quantitative polymerase chain reaction (qPCR). In addition, the Omicron variant and its mutation sites have been fast detected using S gene-specific Cas12a. This study provides an accurate and convenient approach for the real-time surveillance of microbial contamination in sewage water.

Titanium Nitride Modified Fiber Optic Interferometer for Refractive Index Sensitivity Enhancement.

As one of the most well-established biocompatible transition metal nitrides, titanium nitride (TiN) has been widely applied for fiber waveguide coupling device applications. This study proposes a TiN-modified fiber optic interferometer. Benefiting from the unique properties of TiN, including ultrathin nanolayer, high refractive index, and broad-spectrum optical absorption, the refractive index (RI) response of the interferometer is greatly enhanced, which is desired all the time in the field of biosensing. The experimental results show that the deposited TiN nanoparticles (NPs) can enhance the evanescent field excitation and modulate the effective RI difference of the interferometer, which eventually results in the RI response enhancement. Besides, after incorporating the TiN with different concentrations, the resonant wavelength and the RI responses of the interferometer are enhanced to varying degrees. Benefitting from this advantage, the sensing performances, including sensitivity and measurement range, can be flexibly adapted based on different detection requirements. Since RI response can effectively reflect the detection ability of biosensors, the proposed TiN-sensitized fiber optic interferometer can be potentially applied for high-sensitive biosensing applications.

Embedding oxophilic rare-earth single atom in platinum nanoclusters for efficient hydrogen electro-oxidation.

Designing Pt-based electrocatalysts with high catalytic activity and CO tolerance is challenging but extremely desirable for alkaline hydrogen oxidation reaction. Herein we report the design of a series of single-atom lanthanide (La, Ce, Pr, Nd, and Lu)-embedded ultrasmall Pt nanoclusters for efficient alkaline hydrogen electro-oxidation catalysis based on vapor filling and spatially confined reduction/growth of metal species. Mechanism studies reveal that oxophilic single-atom lanthanide species in Pt nanoclusters can serve as the Lewis acid site for selective OH- adsorption and regulate the binding strength of intermediates on Pt sites, which promotes the kinetics of hydrogen oxidation and CO oxidation by accelerating the combination of OH- and *H/*CO in kinetics and thermodynamics, endowing the electrocatalyst with up to 14.3-times higher mass activity than commercial Pt/C and enhanced CO tolerance. This work may shed light on the design of metal nanocluster-based electrocatalysts for energy conversion.

In silico and in vitro study of the adhesion dynamics of erythrophagocytosis in sickle cell disease.

Erythrophagocytosis occurring in the spleen is a critical process for removing senescent and diseased red blood cells (RBCs) from the microcirculation. Although some progress has been made in understanding how the biological signaling pathways mediate the phagocytic processes, the role of the biophysical interaction between RBCs and macrophages, particularly under pathological conditions such as sickle cell disease, has not been adequately studied. Here, we combine computational simulations with microfluidic experiments to quantify RBC-macrophage adhesion dynamics under flow conditions comparable to those in the red pulp of the spleen. We also investigate the RBC-macrophage interaction under normoxic and hypoxic conditions. First, we calibrate key model parameters in the adhesion model using microfluidic experiments for normal and sickle RBCs under normoxia and hypoxia. We then study the adhesion dynamics between the RBC and the macrophage. Our simulation illustrates three typical adhesion states, each characterized by a distinct dynamic motion of the RBCs, namely firm adhesion, flipping adhesion, and no adhesion (either due to no contact with macrophages or detachment from the macrophages). We also track the number of bonds formed when RBCs and macrophages are in contact, as well as the contact area between the two interacting cells, providing mechanistic explanations for the three adhesion states observed in the simulations and microfluidic experiments. Furthermore, we quantify, for the first time to our knowledge, the adhesive forces between RBCs (normal and sickle) and macrophages under different oxygenated conditions. Our results show that the adhesive forces between normal cells and macrophages under normoxia are in the range of 33-58 pN and 53-92 pN for sickle cells under normoxia and 155-170 pN for sickle cells under hypoxia. Taken together, our microfluidic and simulation results improve our understanding of the biophysical interaction between RBCs and macrophages in sickle cell disease and provide a solid foundation for investigating the filtration function of the splenic macrophages under physiological and pathological conditions.

Highly-time-resolved FMCW LiDAR with synchronously-nonlinearity-corrected acquisition for dynamic locomotion.

Highly-time-resolved and precise tracking of position, velocity, and acceleration is urgently required when highly dynamic legged robots are walking, trotting, and jumping. Frequency-modulated continuous-wave (FMCW) laser ranging is able to provide precise measurement in short distance. However, FMCW light detection and ranging (LiDAR) suffers from a low acquisition rate and poor linearity of laser frequency modulation in wide bandwidth. A sub-millisecond-scale acquisition rate and nonlinearity correction in the wide frequency modulation bandwidth have not been reported in previous studies. This study presents the synchronous nonlinearity correction for a highly-time-resolved FMCW LiDAR. The acquisition rate of 20 kHz is obtained by synchronizing the measurement signal and the modulation signal of laser injection current with a symmetrical triangular waveform. The linearization of laser frequency modulation is conducted by resampling of 1000 intervals interpolated in every up-sweep and down-sweep of 25 µs, while measurement signal is stretched or compressed in every period of 50 µs. The acquisition rate is demonstrated to be equal to the repetition frequency of laser injection current for the first time to the best of authors' knowledge. This LiDAR is successfully used to track the foot trajectory of a jumping single-leg robot. The high velocity up to 7.15 m/s and high acceleration of 365 m/s2 are measured during the up-jumping phase, while heavy shock takes place with high acceleration of 302 m/s2 as the foot end strikes the ground. The measured foot acceleration of over 300 m/s2, which is more than 30 times gravity acceleration, is reported on a jumping single-leg robot for the first time.

In silico modeling of patient-specific blood rheology in type 2 diabetes mellitus.

Increased blood viscosity in type 2 diabetes mellitus (T2DM) is a risk factor for the development of insulin resistance and diabetes-related vascular complications; however, individuals with T2DM exhibit heterogeneous hemorheological properties, including cell deformation and aggregation. Using a multiscale red blood cell (RBC) model with key parameters derived from patient-specific data, we present a computational study of the rheological properties of blood from individual patients with T2DM. Specifically, one key model parameter, which determines the shear stiffness of the RBC membrane (µ) is informed by the high-shear-rate blood viscosity of patients with T2DM. At the same time, the other, which contributes to the strength of the RBC aggregation interaction (D0), is derived from the low-shear-rate blood viscosity of patients with T2DM. The T2DM RBC suspensions are simulated at different shear rates, and the predicted blood viscosity is compared with clinical laboratory-measured data. The results show that the blood viscosity obtained from clinical laboratories and computational simulations are in agreement at both low and high shear rates. These quantitative simulation results demonstrate that the patient-specific model has truly learned the rheological behavior of T2DM blood by unifying the mechanical and aggregation factors of the RBCs, which provides an effective way to extract quantitative predictions of the rheological properties of the blood of individual patients with T2DM.

A Static Tin-Manganese Battery with 30000-Cycle Lifespan Based on Stabilized Mn3+/Mn2+ Redox Chemistry.

High-potential Mn3+/Mn2+ redox couple (>1.3 V vs SHE) in a static battery system is rarely reported due to the shuttle and disproportionation of Mn3+ in aqueous solutions. Herein, based on reversible stripping/plating of the Sn anode and stabilized Mn2+/Mn3+ redox couple in the cathode, an aqueous Sn-Mn full battery is established in acidic electrolytes. Sn anode exhibits high deposition efficiency, low polarization, and excellent stability in acidic electrolytes. With the help of H+ and a complexing agent, a reversible conversion between Mn2+ and Mn3+ ions takes place on the graphite surface. Pyrophosphate ligand is initially employed to form a protective layer through a complexation process with Sn4+ on the electrode surface, effectively preventing Mn3+ from disproportionation and hindering the uncontrollable diffusion of Mn3+ to electrolytes. Benefiting from the rational design, the full battery delivers satisfied electrochemical performance including a large capacity (0.45 mAh cm-2 at 5 mA cm-2), high discharge plateau voltage (>1.6 V), excellent rate capability (58% retention from 5 to 30 mA cm-2), and superior cycling stability (no decay after 30 000 cycles). The battery design strategy realizes a robustly stable Mn3+/Mn2+ redox reaction, which broadens research into ultrafast acidic battery systems.

Hydrogel Electrolyte with High Tolerance to a Wide Spectrum of pHs and Compressive Energy Storage Devices Based on It.

Normally, hydrogel electrolytes widely used in flexible energy storage devices have limited tolerance to different pHs. Most gel electrolytes will lose their compressible capability when the adaptable pH is changed. Herein, a poly(acrylamide3 -co-(sulfobetaine methacrylate)1 )@polyacrylamide (P(A3 -co-S1 )@PAM) hydrogel electrolyte equipped with a dual crosslinking network (DN) is successfully fabricated, which exhibits excellent tolerance to any pHs, endowing various energy storage devices including batteries and supercapacitors with superior mechanical durability. The batteries with mild and alkaline P(A3 -co-S1 )@PAM electrolytes display superior stability (over 3000 cycles). Additionally, a Zn||MnO2 battery based on the P(A3 -co-S1 )@PAM hydrogel electrolyte (mild) under 50% compression strain also shows excellent charge-discharge stability and high capacity at 152.4 mAh g-1 after 600 cycles. The strong reversible hydrogen bonds and electrostatic forces originating from zwitterionic structures of poly(sulfobetaine methacrylate) play an important role in dissipating and dispersing energy imposed abruptly. Meanwhile, the zwitterionic structure and intermolecular NH⋯OC hydrogen bonds of the hydrogel lead to the property of acid resistance and alkali resistance. The tough and robust covalent crosslinking bonds and the tight arrangement of DN polymer chains enable the hydrogel electrolytes to recover their initial shape fast once unloading.

Probing the Interaction Between Supercarrier RBC Membrane and Nanoparticles for Optimal Drug Delivery.

Red blood cell (RBC) membrane-hitchhiking nanoparticles (NPs) have been an increasingly popular supercarrier for targeted drug delivery. However, the kinetic details of the shear-induced NP detachment process from RBC in blood flow remain unclear. Here, we perform detailed computational simulations of the traversal dynamics of an RBC-NP composite supercarrier with tunable properties. We show that the detachment of NPs from RBC occurs in a shear-dependent manner which is consistent with previous experiment results. We quantify the NP detachment rate in the microcapillary flow, and our simulation results suggest that there may be an optimal adhesion strength span of 25-40 µJ/m2 for rigid spherical NPs to improve the supercarrier performance and targeting efficiency. In addition, we find that the stiffness and the shape of NPs alter the detachment efficiency by changing the RBC-NP contact areas. Together, these findings provide unique insights into the shear-dependent NP release from the RBC surface, facilitating the clinical utility of RBC-NP composite supercarriers in targeted and localized drug delivery with high precision and efficiency.

Ultrasensitive deafness gene DNA hybridization detection employing a fiber optic Mach-Zehnder interferometer: Enabled by a black phosphorus nanointerface.

The rapid and efficient detection of deafness gene DNA plays an important role in the clinical diagnosis of deafness diseases. This study demonstrates the ultrasensitive detection of complementary DNA (cDNA) by employing a nanointerface-sensitized fiber optic biosensor. The sensor consists of SMF-TNCF-MMF-SMF (abbreviated as STMS) structure with lateral offset. Besides, it is functionalized with a nanointerface of black phosphorus (BP) to enhance the light-matter interaction and eventually improve the sensing performances. Relying on this nanointerface-sensitized sensor, we successfully realize the in-situ detection of cDNA at concentrations ranging from 1 pM to 1 µM, with a sensitivity of 0.719 nm/lgM. The limit of detection (LOD) is as low as 0.24 pM, which is at least two orders of magnitude lower than those of existing methods. The sensor exhibits the advantages of simple operation, fast response, label-free measurement, excellent repeatability, and high selectivity. Our contribution suggests a convenient approach for deafness gene DNA detection and can be extended for general ultra-low concentration DNA detection applications.