Advanced DNA Amplification for Efficient Data Storage.

DNA amplification technologies have significantly advanced biotechnology, particularly in DNA storage. However, adaptation of these technologies to DNA storage poses substantial challenges. Key bottlenecks include achieving high throughput to manage large data sets, ensuring rapid and efficient DNA amplification, and minimizing bias to maintain data fidelity. This perspective begins with an overview of natural and artificial amplification strategies, such as polymerase chain reaction and isothermal amplification, highlighting their respective advantages and limitations. It then explores the prospective applications of these techniques in DNA storage, emphasizing the need to optimize protocols for scalability and robustness in handling diverse digital data. Concurrently, we identify promising avenues, including advancements in enzymatic processes and novel amplification methodologies, poised to mitigate existing constraints and propel the field forward. Ultimately, we provide insights into how to utilize advanced DNA amplification strategies poised to revolutionize the efficiency and feasibility of data storage, ushering in enhanced approaches to data retrieval in the digital age.

Selective Clearance of Circulating Histones Based on Dodecapeptide-Grafted Copolymer Material for Sepsis Blood Purification.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Research indicates that circulating histones, as pathogenic factors, may represent a therapeutic target for sepsis. However, effectively clearing circulating histones poses a challenge due to their structural similarity to normal blood proteins, their low abundance in the bloodstream, and serious interference from other blood biomacromolecules. Here we design a dodecapeptide-based functional polymer that can selectively adsorb circulating histones from the blood. The peptide, named P1 (HNHHQLALVESY), was discovered through phage display screening and demonstrated a strong affinity for circulating histones while exhibiting negligible affinities for common proteins in the blood, such as human serum albumin (HSA), immunoglobulin G (IgG), and transferrin (TRF). Furthermore, the P1 peptide was incorporated into a functional polymer design, poly(PEGMA-co-P1), which was immobilized onto a silica gel surface through reversible addition-fragmentation chain transfer polymerization. The resulting material was characterized using solid nuclear magnetic resonance, thermogravimetric analysis, and X-ray photoelectron spectroscopy. This material demonstrated the ability to selectively and efficiently capture circulating histones from both model solutions and whole blood samples while also exhibiting satisfactory blood compatibility, good antifouling properties, and resistance to interference. Satisfactory binding affinity and efficient capture capacity toward histone were also observed for the other screened peptide P2 (QMSMDLFGSNFV)-grafted polymer, validating phage display as a reliable ligand screening strategy. These findings present an approach for the specific clearance of circulating histones and hold promise for future clinical applications in blood purification toward sepsis.

Hybrid hair follicle stem cell extracellular vesicles co-delivering finasteride and gold nanoparticles for androgenetic alopecia treatment.

Androgenetic alopecia (AGA) is a non-fatal disease prevalent worldwide. However, mixed efficacy has been observed among different therapies for hair regrowth in AGA patients. Thus, a nano-platform with synergistic treatments based on a hybrid extracellular vesicle encapsulating gold nanoparticles (AuNPs) and finasteride (Hybrid/Au@Fi) was constructed through membrane fusion between hair follicle stem cell (HFSC)-derived extracellular vesicles and liposomes. These hybrid vesicles (HVs) not only fuel hair regrowth by providing cellular signals in extracellular vesicles, but also improve storage stability, follicle retention, and drug encapsulation efficiency (EE%) for finasteride inhibiting 5α-reductase, and nano-size AuNPs that simulate low-level laser therapy (LLLT) with similar photothermal effects in vitro. The EE% of finasteride in these HVs reached 45.33%. The dual administration of these extracellular vesicles and finasteride showed a strong synergistic effect on HFSCs in vitro. In an AGA mouse model, once-daily topical Hybrid/Au@Fi (115.07 ± 0.32 nm, -7.50 ± 1.68 mV) gel led to a faster transition of hair follicles (HFs) from the catagen to the anagen, increased hair regrowth coverage, and higher quality of regrowth hair, compared to once-daily 5% minoxidil treatment. Compared to topical minoxidil, the multifaceted synergistic therapy of Hybrid/Au@Fi through topical administration offers a new option for intractable AGA patients with low side effects.

Pre- and postoperative OCT features and surgical outcomes of advanced retinitis pigmentosa with macular hole: case series and literature review.

BACKGROUND: Macular hole (MH) is a rare complication of retinitis pigmentosa (RP) and has an adverse impact on residual visual function. At present, the underlying mechanisms are not fully understood and surgical experience is limited. METHODS: We reviewed the medical records and optical coherence tomography (OCT) scans in a cohort of eight eyes of seven RP patients with MH in order to report their OCT features and vitreoretinal surgical prognosis. RESULTS: This study includes four lamellar macular holes (LMHs) and four full-thickness macular holes (FTMHs). Pre-operative OCT revealed other macular abnormalities in all eyes, such as epiretinal membrane (ERM), cystoid macular edema (CME), lamellar hole-associated epiretinal proliferation (LHEP) and vitreoretinal traction. MH progression and subjective vision worsening were noted in one LMH eye during a seven-month follow-up. All holes closed after vitrectomy with internal limiting membrane (ILM) peeling. At final follow-up, one eye had improved vision and seven eyes remained stable compared to baseline. CONCLUSIONS: The occurrence of MH in RP is accompanied by various imaging characteristics, such as ERM, CME and LHEP, suggesting a multifactorial pathogenesis. Considering poor vision in most RP patients with potentially progressive MH, surgery appears to be effective in maintaining or improving the central vision in a period of time. Thus, vitrectomy should be performed as soon as possible and flap-assisted techniques or episcleral surgeries are needed for some special cases.

Spatial Engineering of Heterotypic Antigens on a DNA Framework for the Preparation of Mosaic Nanoparticle Vaccines with Enhanced Immune Activation against SARS-CoV-2 Variants.

Mosaic nanoparticle vaccines with heterotypic antigens exhibit broad-spectrum antiviral capabilities, but the impact of antigen proportions and distribution patterns on vaccine-induced immunity remains largely unexplored. Here, we present a DNA nanotechnology-based strategy for spatially assembling heterotypic antigens to guide the rational design of mosaic nanoparticle vaccines. By utilizing two aptamers with orthogonal selectivity for the original SARS-CoV-2 spike trimer and Omicron receptor-binding domain (RBD), along with a DNA soccer-ball framework, we precisely manipulate the spacing, stoichiometry, and overall distribution of heterotypic antigens to create mosaic nanoparticles with average, bipolar, and unipolar antigen distributions. Systematic in vitro and in vivo immunological investigations demonstrate that 30 heterotypic antigens in equivalent proportions, with an average distribution, lead to higher production of broad-spectrum neutralizing antibodies compared to the bipolar and unipolar distributions. Furthermore, the precise assembly utilizing our developed methodology reveals that a mere increment of five Omicron RBD antigens on a nanoparticle (from 15 to 20) not only diminishes neutralization against the Omicron variant but also triggers excessive inflammation. This work provides a unique perspective on the rational design of mosaic vaccines by highlighting the significance of the spatial placement and proportion of heterotypic antigens in their structure-activity mechanisms.

Di-caffeoylquinic acid: a potential inhibitor for amyloid-beta aggregation.

Alzheimer's disease (AD) remains a challenging neurodegenerative disorder with limited therapeutic success. Traditional Chinese Medicine (TCM), as a promising new source for AD, still requires further exploration to understand its complex components and mechanisms. Here, focused on addressing Aß (1-40) aggregation, a hallmark of AD pathology, we employed a Thioflavin T fluorescence labeling method for screening the active molecular library of TCM which we established. Among the eight identified, 1,3-di-caffeoylquinic acid emerged as the most promising, exhibiting a robust binding affinity with a KD value of 26.7 nM. This study delves into the molecular intricacies by utilizing advanced techniques, including two-dimensional (2D) 15N-1H heteronuclear single quantum coherence nuclear magnetic resonance (NMR) and molecular docking simulations. These analyses revealed that 1,3-di-caffeoylquinic acid disrupts Aß (1-40) self-aggregation by interacting with specific phenolic hydroxyl and amino acid residues, particularly at Met-35 in Aß (1-40). Furthermore, at the cellular level, the identified compounds, especially 1,3-di-caffeoylquinic acid, demonstrated low toxicity and exhibited therapeutic potential by regulating mitochondrial membrane potential, reducing cell apoptosis, and mitigating Aß (1-40)-induced cellular damage. This study presents a targeted exploration of catechol compounds with implications for effective interventions in AD and sheds light on the intricate molecular mechanisms underlying Aß (1-40) aggregation disruption.

Self-Illuminating Nanoagonist Simultaneously Induces Dual Cell Death Pathways via Death Receptor Clustering for Cancer Therapy.

Inducing death receptor 5 (DR5) clustering holds particular promise in tumor-specific therapeutics because it could trigger an apoptotic cascade in cancerous cells. Herein, we present a tumor microenvironment H2O2-responsive self-illuminating nanoagonist, which could induce dual tumor cell death pathways through enhancing DR5 clustering. By conjugating DR5 ligand peptides onto the surfaces of self-illuminating nanoparticles with cross-linking capacity, this strategy not only provides scaffolds for ligands to bind receptors but also cross-links them through photo-cross-linking. This strategy allows for efficient activation of DR5 downstream signaling, initiating the extrinsic apoptosis pathway and immunogenic cell death of tumor cells, and contributes to improved tumor-specific immune responses, resulting in enhanced antitumor efficacy and minimized systemic adverse effects.

Observation of structural and vascular features of retina and choroid in myopia using ultra-widefield SS-OCTA.

BACKGROUND: To find the relationship between the changes of retinal and choriodal structure/ vascular densities (VD) and the myopia progress. METHODS: 126 eyes of 126 age-matched young participants were divided into three groups: Emmetropia and Low Myopia (EaLM) (33 eyes), Moderate Myopia (MM) (39 eyes), and High Myopia (HM) (54 eyes). Fundus images measuring 12 × 12 mm were captured using ultra-widefield swept-source optical coherence tomography angiography (SS-OCTA). Each image was uniformly divided into nine regions: supra-temporal (ST), temporal (T), infra-temporal (IT), superior (S), central macular area (C), inferior (I), supra-nasal (SN), nasal (N), and infra-nasal (IN). Various structural parameters, including inner retina thickness (IRT), outer retina thickness (ORT), and choroid thickness (CT), were assessed, and the VD of the superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaries (CC), and choroid vessels (ChdV) were quantified. RESULTS: CT in upper fundus exhibited a significant reduction from EaLM to MM. Additionally, ORT (ST, S. SN, C, N, IT, I, IN), CT (ST, S, SN, T, C, N, IT, I, IN) and VDs of SCP (ST, S, C, I, IN), DCP (ST, S, T, C, I) and ChdV (T, N, I, IN) were statistically diminished in EaLM compared to HM. Furthermore, IRT (N), ORT (N, IN), CT (S, SN, T, C, IT, I) and VDs of SCP (I, IN) and DCP (I) exhibited significant decreases as MM progressed towards HM. Intriguingly, there was a notable increase in the VD of CC (ST, S, T, C, N) as myopia progressed from MM to HM. CONCLUSION: Significant changes in retinal and choroid structure and vascular density occur as moderate myopia advances to high myopia. Efforts to curb myopia progression to this stage are essential, as the failure to do so may lead to the development of corresponding retinopathy.

An injectable thermosensitive hyaluronic acid/pluronic F-127 hydrogel for deep penetration and combination therapy of frozen shoulder.

Frozen shoulder (FS) is a common and progressive shoulder disorder that causes glenohumeral joint stiffness, characterized by inflammation and fibrosis. The treatment options are quite limited, and the therapeutic response is hindered by the fibrous membrane formed by excessive collagen and the rapid removal by synovial fluid. To address these challenges, we designed a hyaluronic acid/Pluronic F-127 (HP)-based injectable thermosensitive hydrogel as a drug carrier loaded with dexamethasone and collagenase (HPDC). We screened for an optimal HP hydrogel that can sustain drug release for approximately 10 days both in vitro and in vivo. In the meanwhile, we found that HP hydrogel could inhibit the proliferation and diminish the adhesion capacity of rat synovial cells induced by transforming growth factor-ß1. Furthermore, using an established immobilization rat model of FS, intra-articular injection of HPDC significantly improved joint range of motion compared to medication alone. Relying on sustained drug release, the accumulated collagen fibers were degraded by collagenase to promote the deep delivery of dexamethasone. These findings showed a positive combined treatment effect of HPDC, providing a novel idea for the comprehensive treatment of FS.

Thresholds and extent of temperature effects on maize yield differ in different grain-filling stages.

Temperature is a vital environmental factor affecting grain filling and maize yield. The response of maize yield to temperature at different stages of grain filling, however, remains uncharacterized. This study used "Zhengdan 958" as the test material to analyze the high-temperature threshold and yield sensitivity of grain-filling in different periods without water stress by using the data from staging sowing experiments at agro-meteorological experimental stations in Hebi and Suzhou in the Huang-Huai-Hai Plain from 2019 to 2022. The results demonstrated that: (1) the maximum temperature threshold was different in various periods of maize grain-filling in the Huang-Huai-Hai Plain, showing the early grain-filling period (EP) > the active grain-filling period (AP) > the late grain-filling period (LP). With the largest differences in temperature thresholds found in AP, the maximum temperature threshold of AP can better reflect the characteristics of grain filling rather than the whole filling period. (2) The heat of the grain-filling period can explain more than 80 % of the yield variation and affect the yield by influencing the number of days required to reach the maximum grain-filling rate (Vmaxd) and the duration of the active grain-filling period (DAP). (3) The growing degree days (GDD) is the most significant controlling factor affecting yield; however, the effect of heat degree days (HDD) cannot be ignored. The HDD and cumulative thresholds of HDD in the EP and AP of grain-filling can better reflect the effect of heat on yield. The accumulation thresholds of HDD at Hebi and Suzhou were 28.1 °C·d and 15.2 °C·d in the EP period, and 31.0 °C·d and 14.9 °C·d in the AP period, respectively. The results provide a basis for the precise identification of heat disasters during grain-filling and the scientific adjustment of sowing dates.

Decoding Biomechanical Cues Based on DNA Sensors.

Biological systems perceive and respond to mechanical forces, generating mechanical cues to regulate life processes. Analyzing biomechanical forces has profound significance for understanding biological functions. Therefore, a series of molecular mechanical techniques have been developed, mainly including single-molecule force spectroscopy, traction force microscopy, and molecular tension sensor systems, which provide indispensable tools for advancing the field of mechanobiology. DNA molecules with a programmable structure and well-defined mechanical characteristics have attached much attention to molecular tension sensors as sensing elements, and are designed for the study of biomechanical forces to present biomechanical information with high sensitivity and resolution. In this work, a comprehensive overview of molecular mechanical technology is presented, with a particular focus on molecular tension sensor systems, specifically those based on DNA. Finally, the future development and challenges of DNA-based molecular tension sensor systems are looked upon.

Enhanced portable detection for Sars-CoV-2 utilizing DNA tetrahedron-tethered aptamers and a pressure meter.

Tethering oligonucleotide aptamers to a DNA tetrahedron structure can enhance the recognition of SARS-CoV-2 spike protein to effectively overcome challenges with its detection in current diagnostic assays. Building on this framework, we have developed a unique portable detection method for COVID-19 that provides exceptional sensitivity and selectivity via pressure meter readout. This innovative assay streamlines the detection process, providing a rapid, sensitive, cost-effective, and user-friendly diagnostic tool. This point-of-care test exhibits high sensitivity and specificity, achieving an impressive detection limit of 0.1 pg mL-1 for the spike protein. The effectiveness of this method was validated using pseudoviruses and oropharyngeal swab samples, and its utility for environmental monitoring is demonstrated by testing sewage samples. With a wide linear range and strong potential for clinical or home application, our assay represents a major innovation in point-of-care diagnostics and provides a vital contribution to the current toolkit for controlling the impacts of COVID-19.

Sialic Acid-Functionalized Pyroptosis Nanotuner for Epigenetic Regulation and Enhanced Cancer Immunotherapy.

The efficacy of immune checkpoint blockade (ICB) in promoting an immune response against tumors still encounters challenges such as low response rates and off-target effects. Pyroptosis, an immunogenic cell death (ICD) mechanism, holds the potential to overcome the limitations of ICB by activating and recruiting immune cells. However, the expression of the pyroptosis-related protein Gasdermin-E(GSDME) in some tumors is limited due to mRNA methylation. To overcome this obstacle, sialic acid-functionalized liposomes coloaded with decitabine, a demethylation drug, and triclabendazole, a pyroptosis-inducing drug are developed. This nanosystem primarily accumulates at tumor sites via sialic acid and the Siglec receptor, elevating liposome accumulation in tumors up to 3.84-fold at 24 h and leading to the upregulation of pyroptosis-related proteins and caspase-3/GSDME-dependent pyroptosis. Consequently, it facilitates the infiltration of CD8+ T cells into the tumor microenvironment and enhances the efficacy of ICB therapy. The tumor inhibition rate of the treatment group is 89.1% at 21 days. This study highlights the potential of sialic acid-functionalized pyroptosis nanotuners as a promising approach for improving the efficacy of ICB therapy in tumors with low GSDME expression through epigenetic alteration and ICD.

Anti-VEGFR2 F(ab')2 drug conjugate promotes renal accumulation and glomerular repair in diabetic nephropathy.

Poor renal distribution of antibody-based drugs is the key factor contributing to low treatment efficiency for renal diseases and side effects. Here, we prepare F(ab')2 fragmented vascular endothelial growth factor receptor 2 antibody (anti-VEGFR2 (F(ab')2) to block VEGFR2 overactivation in diabetic nephropathy (DN). We find that the anti-VEGFR2 F(ab')2 has a higher accumulation in DN male mice kidneys than the intact VEGFR2 antibody, and simultaneously preserves the binding ability to VEGFR2. Furthermore, we develop an antibody fragment drug conjugate, anti-VEGFR2 F(ab')2-SS31, comprising the anti-VEGFR2 F(ab')2 fragment linked to the mitochondria-targeted antioxidant peptide SS31. We find that introduction of SS31 potentiates the efficacy of anti-VEGFR2 F(ab')2. These findings provide proof of concept for the premise that antibody fragment drug conjugate improves renal distribution and merits drug validation in renal disease therapy.

Effects of low-dose levothyroxine on atrial natriuretic peptide and c-type natriuretic peptide in children with neonatal hypothyroidism.

OBJECTIVE: This study was designed to explore the effects of low-dose levothyroxine (LT4) on levels of atrial natriuretic peptide (ANP) and c-type natriuretic peptide (CNP) in neonates with hypothyroidism (NH). METHODS: In this retrospective study, a total of 90 cases of NH screened out and confirmed by the First Affiliated Hospital of Zhejiang Chinese Medical University from October 2014 to February 2018 were selected as a study group. 80 healthy children who underwent physical examination during the same time period were enrolled as controls. Before and after treatment with LT4, the changes in the levels of serum thyroid stimulating hormone (TSH) and free thyroxine (FT4) were observed, and the changes in the levels of ANP and CNP and their relationships to clinical efficacy were evaluated. Additionally, the growth and development of body and the scores of the China-Wechsler Younger Children Scale of Intelligence (C-WYCSI) were compared before and after the treatment, and the changes in the cardiac functions of children in the study group were evaluated. Independent risk factors for mental abnormality after treatment were analyzed by logistic regression. RESULTS: After treatment, TSH levels in patients declined, while the levels of T3, T4, free triiodothyronine (FT3), and FT4 increased, without significant differences between groups. After treatment, ANP levels in patients increased but CNP levels decreased. ANP levels were negatively correlated with clinical efficacy, but CNP levels were positively correlated with it. Ultrasonic cardiography showed the improved cardiac functions. After treatment, the growth and development of body and the C-WYCSI scores increased compared to those before treatment. First visit date, T3, FT4, TSH were independent risk factors for mental disorders in children. CONCLUSION: For children with NH, low-dose LT4 can correct the level of thyroid function, promote physical and mental development, and improve the levels of ANP and CNP.

Anti-Kelch-like protein 11 antibody encephalitis: a case report and literature review.

Anti-Kelch-like protein 11 (KLHL11) antibody encephalitis is a rare clinical condition characterized by autoimmune-mediated encephalomyelitis associated with the presence of KLHL11 antibodies. Diagnosis requires the detection of serum and cerebrospinal fluid anti-KLHL11 antibodies, while immunotherapy serves as the principal treatment approach. This paper presents a case report highlighting the emergence of anti-KLHL11 antibody encephalitis. A 66-year-old male patient presented with seizures, impaired cognitive function, disturbance of consciousness, apathy, hypologia, dysphoria, and ataxia. Serum and cerebrospinal fluid (CSF) were identified as positive for anti-KLHL11 antibodies, leading to a diagnosis of autoimmune encephalitis associated with KLHL11 antibodies. After treatment with glucocorticoid, the patient did not experience further convulsions and recovered consciousness, with improved cognitive function. Tumor screening suggested the presence of an underlying malignancy. The clinical manifestations of anti-KLHL11 antibody encephalitis vary widely, and timely identification and treatment can improve prognosis.

Aptamer-Assisted Blockade of the Immune Suppressor Sialic Acid-Binding Immunoglobulin-Like Lectin-15 for Cancer Immunotherapy.

The percentage of low response and adaptive resistance to current antibody-based immune checkpoint blockade (ICB) therapy requires the development of novel immunotherapy strategies. Here, we developed an aptamer-assisted immune checkpoint blockade (Ap-ICB) against sialic acid-binding immunoglobulin-like lectin-15 (Siglec-15), a novel immune suppressor broadly upregulated on cancer cells and tumor infiltrating myeloid cells, which is mutually exclusive of programmed cell death ligand 1 (PD-L1). Using protein aptamer selection, we identified WXY3 aptamer with high affinity against Siglec-15 protein/Siglec-15 positive cells. We demonstrated that WXY3 aptamer rescued antigen-specific T cell responses in vitro and in vivo. Importantly, the WXY3 Ap-ICB against Siglec-15 amplified anti-tumor immunity in the tumor microenvironment and inhibited tumor growth/metastasis in syngeneic mouse model, which may result from enhanced macrophage and T cell functionality. In addition, by using aptamer-based spherical nucleic acids, we developed a synergetic ICB strategy of multivalent binding and steric hindrance, which further improves the in vivo anti-tumor effect. Taken together, our results support Ap-ICB targeted Siglec-15 as a potential strategy for normalization cancer immunotherapy.

Microfluidic Enrichment of Intact SARS-CoV-2 Viral Particles by Stoichiometric Balanced DNA Computation.

Health diagnostic tools for community safety and environmental monitoring require selective and quantitatively accurate active viral load assessment. Herein, we report a microfluidic enrichment strategy to separate intact SARS-CoV-2 particles by AND logic gate with inputs of cholesterol oligonucleotides for the envelope and aptamers for the spike viral proteins. Considering the unequal quantity of endogenous spikes and lipid membranes on SARS-CoV-2, a dual-domain binding strategy, with two aptamers targeting different spike domains, was applied to balance the spike-envelope stoichiometric ratio. By balancing the stoichiometric with DNA computation and promoting microscale mass transfer of the herringbone chip, the developed strategy enabled high sensitivity detection of pseudotyped SARS-CoV-2 with a limit of detection as low as 37 active virions/µL while distinguishing it from inactive counterparts, other nontarget viruses, and free spike protein. Moreover, the captured viral particles can be released through DNase I treatment with up to 90% efficiency, which is fully compatible with virus culture and sequencing. Overall, the developed strategy not only identified SARS-CoV-2-infected patients (n = 14) with 100% identification from healthy donors (n = 8) but also provided a fresh perspective on the regulation of stoichiometric ratio to achieve a more biologically relevant DNA computation.

Capturing nascent extracellular vesicles by metabolic glycan labeling-assisted microfluidics.

Extracellular vesicle (EV) secretion is a dynamic process crucial to cellular communication. Temporally sorting EVs, i.e., separating the newly-produced ones from the pre-existing, can allow not only deep understanding of EV dynamics, but also the discovery of potential EV biomarkers that are related to disease progression or responsible to drug intervention. However, the high similarity between the nascent and pre-existing EVs makes temporal separation extremely challenging. Here, by co-translational introduction of azido groups to act as a timestamp for click chemistry labelling, we develop a microfluidic-based strategy to enable selective isolation of nascent EVs stimulated by an external cue. In two mouse models of anti-PD-L1 immunotherapy, we demonstrate the strategy's feasibility and reveal the high positive correlation of nascent PD-L1+ EV level to tumor volume, suggesting an important role of nascent EVs in response to immunotherapy in cancer treatment.

Hierarchical Fluid Interface Enables Spatiotemporal Regulation of Ligand Distribution to Increase Kinetics and Thermodynamics of Interfacial Binding Reaction.

In nature, regulation of the spatiotemporal distribution of interfacial receptors and ligands leads to optimum binding kinetics and thermodynamics of receptor-ligand binding reactions within interfaces. Inspired by this, we report a hierarchical fluid interface (HieFluidFace) to regulate the spatiotemporal distribution of interfacial ligands to increase the rate and thermodynamic favorability of interfacial binding reactions. Each aptamer-functionalized gold nanoparticle, termed spherical aptamer (SAPT), is anchored on a supported lipid bilayer without fluidity, like an "island", and is surrounded by many fluorescent aptamers (FAPTs) with free fluidity, like "rafts". Such ligand "island-rafts" model provides a large reactive cross-section for rapid binding to cellular receptors. The synergistic multivalency of SAPTs and FAPTs improves interfacial affinity for tight capture. Moreover, FAPTs accumulate at binding sites to bind to cellular receptors with clustered fluorescence to "lighten" cells for direct identification. Thus, HieFluidFace in a microfluidic chip achieves high-performance capture and identification of circulating tumor cells from clinical samples, providing a new paradigm to optimize the kinetics and thermodynamics of interfacial binding reactions.