Precessing jet nozzle connecting to a spinning black hole in M87.

The nearby radio galaxy M87 offers a unique opportunity to explore the connections between the central supermassive black hole and relativistic jets. Previous studies of the inner region of M87 revealed a wide opening angle for the jet originating near the black hole1-4. The Event Horizon Telescope resolved the central radio source and found an asymmetric ring structure consistent with expectations from general relativity5. With a baseline of 17 years of observations, there was a shift in the jet's transverse position, possibly arising from an 8- to 10-year quasi-periodicity3. However, the origin of this sideways shift remains unclear. Here we report an analysis of radio observations over 22 years that suggests a period of about 11 years for the variation in the position angle of the jet. We infer that we are seeing a spinning black hole that induces the Lense-Thirring precession of a misaligned accretion disk. Similar jet precession may commonly occur in other active galactic nuclei but has been challenging to detect owing to the small magnitude and long period of the variation.

Limited resection is comparable to lobectomy for tumor size ≤ 2 cm pulmonary invasive mucinous adenocarcinoma.

OBJECTIVES: Invasive mucinous adenocarcinoma (IMA) has a rare incidence with better prognosis than nonmucinous adenocarcinoma. We aimed to investigate the prognosis between limited resection and lobectomy for patients with clinical stage IA IMA ≤ 2 cm. METHODS: Data were taken from two cohorts: In Shanghai Pulmonary Hospital (SPH) corhort, we identified 403 patients with clinical stage IA IMA who underwent surgery. In the SEER corhort, 480 patients with stage T1 IMA who after surgery were included. Recurrence-free survival (RFS) for SPH corhort, lung cancer-specific survival (LCSS) for the SEER corhort and overall survival (OS) for both corhort were compared between patients undergoing lobectomy and limited resection by Log-rank and Cox proportional hazard regression model. RESULTS: In SPH corhort, patients who underwent limited resection had equivalent prognosis than those underwent lobectomy (5-year RFS: 79.3% versus. 82.6%, p = 0.116; 5-year OS: 86.2% versus. 88.3%, p = 0.235). However, patients with IMA > 2 to 3 cm had worse prognosis than those with IMA ≤ 2 cm (5-year RFS: 73.7% versus. 86.1%, p = 0.007). In the analysis of IMA > 2 to 3 cm subgroup, multivariate analysis showed that limited resection was an independent risk factor of RFS (hazard ratio, 2.417; 95% confidence interval, 1.157-5.049; p = 0.019), while OS (p = 0.122) was not significantly different between two groups. For IMA ≤ 2 cm, limited resection was not a risk factor of RFS (p = 0. 953) and OS (p = 0.552). In the SEER corhort, IMA ≤ 2 cm subgroup, limited resection was equivalent prognosis in LCSS (p = 0.703) and OS (p = 0.830). CONCLUSIONS: Limited resection could be a potential surgical option which comparable to lobectomy in patients with clinical stage IA IMA ≤ 2 cm.

Incidence and survival analyses for occult lung cancer between 2004 and 2015: a population-based study.

BACKGROUND: This study aimed to investigate the incidence and long-term survival outcomes of occult lung cancer between 2004 and 2015. METHODS: A total of 2958 patients were diagnosed with occult lung cancer in the 305,054 patients with lung cancer. The entire cohort was used to calculate the crude incidence rate. Eligible 52,472 patients (T1-xN0M0, including 2353 occult lung cancers) were selected from the entire cohort to perform survival analyses after translating T classification according to the 8th TNM staging system. Cancer-specific survival curves for different T classifications were presented. RESULTS: The crude incidence rate of occult lung cancer was 1.00 per 100 patients, and it was reduced between 2004 and 2015 [1.4 per 100 persons in 2004; 0.6 per 100 persons in 2015; adjusted risk ratio = 0.437, 95% confidence interval (CI) 0.363-0.527]. In the survival analysis, there were 2206 death events in the 2353 occult lung cancers. The results of the multivariable analysis revealed that the prognoses with occult lung cancer were similar to patients with stage T3N0M0 (adjusted hazard ratio = 1.054, 95% CI 0.986-1.127, p = 0.121). Adjusted survival curves presented the same results. In addition, adjusted for other confounders, female, age ≤ 72 years, surgical treatment, radiotherapy, adenocarcinoma, and non-squamous and non-adenocarcinoma non-small cell carcinoma were independent protective prognostic factors (all p < 0.05). CONCLUSIONS: Occult lung cancer was uncommon. However, the cancer-specific survival of occult lung cancer was poor, therefore, we should put the assessment of its prognoses on the agenda. Timely surgical treatment and radiotherapy could improve survival outcomes for those patients. Besides, we still need more research to confirm those findings.

Effective Light Directed Assembly of Building Blocks with Microscale Control.

Light-directed forces have been widely used to pattern micro/nanoscale objects with precise control, forming functional assemblies. However, a substantial laser intensity is required to generate sufficient optical gradient forces to move a small object in a certain direction, causing limited throughput for applications. A high-throughput light-directed assembly is demonstrated as a printing technology by introducing gold nanorods to induce thermal convection flows that move microparticles (diameter = 40 µm to several hundreds of micrometers) to specific light-guided locations, forming desired patterns. With the advantage of effective light-directed assembly, the microfluidic-fabricated monodispersed biocompatible microparticles are used as building blocks to construct a structured assembly (≈10 cm scale) in ≈2 min. The control with microscale precision is approached by changing the size of the laser light spot. After crosslinking assembly of building blocks, a novel soft material with wanted pattern is approached. To demonstrate its application, the mesenchymal stem-cell-seeded hydrogel microparticles are prepared as functional building blocks to construct scaffold-free tissues with desired structures. This light-directed fabrication method can be applied to integrate different building units, enabling the bottom-up formation of materials with precise control over their internal structure for bioprinting, tissue engineering, and advanced manufacturing.

Achieving Ultrahigh Electrocaloric Response in (Bi0.5Na0.5)TiO3-Based Ceramics through B-Site Defect Engineering.

Lead-free electrocaloric (EC) ferroelectrics are considered ideal for the next generation of environmentally friendly solid-state refrigeration materials. However, their inferior performance compared to lead-based materials significantly restricts their potential application. According to phase-field simulations, it is predicted that the pinning effect of a moderate number of defects can effectively enhance the reversible polarization response associated with the entropy change. Herein, sodium-bismuth titanate (BNT) ceramics with high spontaneous polarization are selected to construct B-site defects by introducing Li+ and Nb5+. Under an electric field of 6 kV mm-1, ultrahigh EC temperature changes of ΔTpos = 1.77 and ΔTneg = 1.49 K are achieved at 65 °C by direct measurement (ΔTneg > 1 K over 55-120 °C). Furthermore, ΔTneg remains above 0.70 K in the temperature range from 25 to 130 °C, exhibiting immense potential for practical applications. This study offers a promising direction for optimizing the EC response in defect systems.

A bioinspired surface tension-driven route toward programmed cellular ceramics.

The intriguing biomineralization process in nature endows the mineralized biological materials with intricate microarchitected structures in a facile and orderly way, which provides an inspiration for processing ceramics. Here, we propose a simple and efficient manufacturing process to fabricate cellular ceramics in programmed cell-based 3D configurations, inspired by the biomineralization process of the diatom frustule. Our approach separates the ingredient synthesis from architecture building, enabling the programmable manufacturing of cellular ceramics with various cell sizes, geometries, densities, metastructures, and constituent elements. Our approach exploits surface tension to capture precursor solutions in the architected cellular lattices, allowing us to control the liquid geometry and manufacture cellular ceramics with high precision. We investigate the geometry parameters for the architected lattices assembled by unit cells and unit columns, both theoretically and experimentally, to guide the 3D fluid interface creation in arranged configurations. We manufacture a series of globally cellular and locally compact piezoceramics, obtaining an enhanced piezoelectric constant and a designed piezoelectric anisotropy. This bioinspired, surface tension-assisted approach has the potential to revolutionize the design and processing of multifarious ceramic materials for structural and functional applications in energy, electronics and biomedicine.

Ultrauniform, strong, and ductile 3D-printed titanium alloy through bifunctional alloy design.

Coarse columnar grains and heterogeneously distributed phases commonly form in metallic alloys produced by three-dimensional (3D) printing and are often considered undesirable because they can impart nonuniform and inferior mechanical properties. We demonstrate a design strategy to unlock consistent and enhanced properties directly from 3D printing. Using Ti-5Al-5Mo-5V-3Cr as a model alloy, we show that adding molybdenum (Mo) nanoparticles promotes grain refinement during solidification and suppresses the formation of phase heterogeneities during solid-state thermal cycling. The microstructural change because of the bifunctional additive results in uniform mechanical properties and simultaneous enhancement of both strength and ductility. We demonstrate how this alloy can be modified by a single component to address unfavorable microstructures, providing a pathway to achieve desirable mechanical characteristics directly from 3D printing.

Scaffold-Free Tracheal Engineering via a Modular Strategy Based on Cartilage and Epithelium Sheets.

Tracheal defects lead to devastating problems, and practical clinical substitutes that have complex functional structures and can avoid adverse influences from exogenous bioscaffolds are lacking. Herein, a modular strategy for scaffold-free tracheal engineering is developed. A cartilage sheet (Cart-S) prepared by high-density culture is laminated and reshaped to construct a cartilage tube as the main load-bearing structure in which the chondrocytes exhibit a stable phenotype and secreted considerable cartilage-specific matrix, presenting a native-like grid arrangement. To further build a tracheal epithelial barrier, a temperature-sensitive technique is used to construct the monolayer epithelium sheet (Epi-S), in which the airway epithelial cells present integrated tight junctions, good transepithelial electrical resistance, and favorable ciliary differentiation capability. Epi-S can be integrally transferred to inner wall of cartilage tube, forming a scaffold-free complex tracheal substitute (SC-trachea). Interestingly, when Epi-S is attached to the cartilage surface, epithelium-specific gene expression is significantly enhanced. SC-trachea establishes abundant blood supply via heterotopic vascularization and then is pedicle transplanted for tracheal reconstruction, achieving 83.3% survival outcomes in rabbit models. Notably, the scaffold-free engineered trachea simultaneously satisfies sufficient mechanical properties and barrier function due to its matrix-rich cartilage structure and well-differentiated ciliated epithelium, demonstrating great clinical potential for long-segmental tracheal reconstruction.

Prognostic assessment of lung adenocarcinoma patients with early-staging diseases: a nomogram based on coagulation-related factors.

OBJECTIVES: Early-stage lung adenocarcinoma (ADC) has a great heterogeneity in prognosis that is difficult to evaluate effectively. Thus, we developed and validated an effective nomogram prognostic model based on the clinical and laboratory characteristics of stage I-IIA ADC. METHODS: We included 1585 patients with pathologically diagnosed stage I-IIA ADC who underwent surgery at Shanghai Pulmonary Hospital. The nomogram was constructed based on the peripheral blood test and coagulation test indicators and evaluated using Calibration plots, concordance index, decision curve analysis and the X-tile software. Recurrence-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier method and the Cox proportional hazard regression model. The primary end point of this study was RFS. RESULTS: Thrombin time and 4 clinical indicators for RFS were integrated into nomograms. A favourable agreement between the nomogram prediction and validation was observed in the calibration curves for RFS probabilities. The concordance index of the nomogram to predict RFS was 0.736 (95% confidence interval, 0.717-0.755). Moreover, significant differences were shown between the high-risk and low-risk groups in RFS and OS (P < 0.001) after effective cut-off values of risk points were found based on the nomogram. CONCLUSIONS: We established and validated a prognostic nomogram including thrombin time to predict RFS and OS of stage I-IIA ADC patients. This nomogram provided an effective prediction ability for the prognosis of stage I-IIA ADC patients.

Tough soldering for stretchable electronics by small-molecule modulated interfacial assemblies.

The rapid-developing soft robots and wearable devices require flexible conductive materials to maintain electric functions over a large range of deformations. Considerable efforts are made to develop stretchable conductive materials; little attention is paid to the frequent failures of integrated circuits caused by the interface mismatch of soft substrates and rigid silicon-based microelectronics. Here, we present a stretchable solder with good weldability that can strongly bond with electronic components, benefiting from the hierarchical assemblies of liquid metal particles, small-molecule modulators, and non-covalently crosslinked polymer matrix. Our self-solder shows high conductivity (>2×105 S m-1), extreme stretchability (~1000%, and >600% with chip-integrated), and high toughness (~20 MJ m-3). Additionally, the dynamic interactions within our solder's surface and interior enable a range of unique features, including ease of integration, component substitution, and circuit recyclability. With all these features, we demonstrated an application as thermoforming technology for three-dimensional (3D) conformable electronics, showing potential in reducing the complexity of microchip interfacing, as well as scalable fabrication of chip-integrated stretchable circuits and 3D electronics.

Fast and versatile electrostatic disc microprinting for piezoelectric elements.

Nanoparticles, films, and patterns are three critical piezoelectric elements with widespread applications in sensing, actuations, catalysis and energy harvesting. High productivity and large-area fabrication of these functional elements is still a significant challenge, let alone the control of their structures and feature sizes on various substrates. Here, we report a fast and versatile electrostatic disc microprinting, enabled by triggering the instability of liquid-air interface of inks. The printing process allows for fabricating lead zirconate titanate free-standing nanoparticles, films, and micro-patterns. The as-fabricated lead zirconate titanate films exhibit a high piezoelectric strain constant of 560 pm V-1, one to two times higher than the state-of-the-art. The multiplexed tip jetting mode and the large layer-by-layer depositing area can translate into depositing speeds up to 109 µm3 s-1, one order of magnitude faster than current techniques. Printing diversified functional materials, ranging from suspensions of dielectric ceramic and metal nanoparticles, to insulating polymers, to solutions of biological molecules, demonstrates the great potential of the electrostatic disc microprinting in electronics, biotechnology and beyond.

One-wire reconfigurable and damage-tolerant sensor matrix inspired by the auditory tonotopy.

Sensor matrices are essential in various fields including robotics, aviation, health care, and industrial machinery. However, conventional sensor matrix systems often face challenges such as limited reconfigurability, complex wiring, and poor robustness. To address these issues, we introduce a one-wire reconfigurable sensor matrix that is capable of conforming to three-dimensional curved surfaces and resistant to cross-talk and fractures. Our frequency-located technology, inspired by the auditory tonotopy, reduces the number of output wires from row × column to a single wire by superimposing the signals of all sensor units with unique frequency identities. The sensor units are connected through a shared redundant network, giving great freedom for reconfiguration and facilitating quick repairs. The one-wire frequency-located technology is demonstrated in two applications-a pressure sensor matrix and a pressure-temperature multimodal sensor matrix. In addition, we also show its potential in monitoring strain distribution in an airplane wing, emphasizing its advantages in simplified wiring and improved robustness.

A bioengineered trachea-like structure improves survival in a rabbit tracheal defect model.

A practical strategy for engineering a trachea-like structure that could be used to repair or replace a damaged or injured trachea is an unmet need. Here, we fabricated bioengineered cartilage (BC) rings from three-dimensionally printed fibers of poly(ɛ-caprolactone) (PCL) and rabbit chondrocytes. The extracellular matrix (ECM) secreted by the chondrocytes combined with the PCL fibers formed a "concrete-rebar structure," with ECM deposited along the PCL fibers, forming a grid similar to that of native cartilage. PCL fiber-hydrogel rings were then fabricated and alternately stacked with BC rings on silicone tubes. This trachea-like structure underwent vascularization after heterotopic transplantation into rabbits for 4 weeks. The vascularized bioengineered trachea-like structure was then orthotopically transplanted by end-to-end anastomosis to native rabbit trachea after a segment of trachea had been resected. The bioengineered trachea-like structure displayed mechanical properties similar to native rabbit trachea and transmural angiogenesis between the rings. The 8-week survival rate in transplanted rabbits was 83.3%, and the respiratory rate of these animals was similar to preoperative levels. This bioengineered trachea-like structure may have potential for treating tracheal stenosis and other tracheal injuries.

Extracellular Vesicles in Tissue Engineering: Biology and Engineered Strategy.

Extracellular vesicles (EVs), acting as an important ingredient of intercellular communication through paracrine actions, have gained tremendous attention in the field of tissue engineering (TE). Moreover, these nanosized extracellular particles (30-140 nm) can be incorporated into biomaterials according to different principles to facilitate signal delivery in various regenerative processes directly or indirectly. Bioactive biomaterials as the carrier will extend the retention time and realize the controlled release of EVs, which further enhance their therapeutic efficiency in tissue regeneration. Herein, the basic biological characteristics of EVs are first introduced, and then their outstanding performance in exerting direct impacts on target cells in tissue regeneration as well as indirect effects on promoting angiogenesis and regulating the immune environment, due to specific functional components of EVs (nucleic acid, protein, lipid, etc.), is emphasized. Furthermore, different design ideas for suitable EV-loaded biomaterials are also demonstrated. In the end, this review also highlights the engineered strategies, which aim at solving the problems related to natural EVs such as highly heterogeneous functions, inadequate tissue targeting capabilities, insufficient yield and scalability, etc., thus promoting the therapeutic pertinence and clinical potential of EV-based approaches in TE.

A Simple and Efficient Strategy for Preparing a Cell-Spheroid-Based Bioink.

Cell spheroids are a promising bioprinting building block that can mimic several physiological conditions in embryonic development. However, it remains challenging to efficiently prepare cell-spheroid-based bioink (Sph-bioink) with favorable printability and spheroid fusion ability. In this work, a poly(N-isopropylacrylamide) (PNIPAAm)-based porous hydrogel is developed as an "all-in-one" platform for Sph-bioink preparation. On the one hand, the nonadhesive porous structure in hydrogels is an effective tool for fabricating adipose-derived stem cell (ASC) spheroids in high yield, and the hydrogel itself also serves as a "carrier" for conveniently transferring cell spheroids to the bioprinter. On the other hand, the integration of redox/thermo-responsiveness allows the hydrogel to shift from a solid spheroid-making tool to an extrudable bioprinting medium that is sensitive to temperature. These features enabled a simple procedure for preparing Sph-bioink, in which the cell spheroids were densely packed to retain fusion capability. The present study also demonstrates that ASC spheroids formed in hydrogels have good biological preservation and superior chondrogenic differentiation, and verified the feasibility of using Sph-bioink to build custom-shaped mature cartilage. In conclusion, this strategy provides a simple, efficient, and standardized approach for Sph-bioink preparation, making it possible to produce tissue-engineered constructs with accelerated maturation and functionalization.

3D Conformal Fabrication of Piezoceramic Films.

Piezoceramic films are an essential class of energy-conversion materials that have been widely used in the electronics industry. Although current methods create a great freedom for fabricating high-quality piezoceramic films, it requires well-controlled synthesis conditions, including special high-cost equipment and planar substrates particularly. The limited substrate selections hinder the applications of piezoceramic films in 3D conformal structures where most objects possess complex curvilinear surfaces. To overcome such limitations, a fast, energy-efficient, and cost-effective approach, named flame treated spray (FTS) coating, is developed for preparing piezoceramic films on free-form surfaces. The flame treatment significantly enhances the hydrophilicity of a substrate, assisting in forming a uniform and continuous thin film. The followed spray coating deposits hundreds of nanometers to several micrometers thick films on 3D free-form surfaces. Given the size controllability and arbitrary surface compatibility of the FTS method, a highly conformal piezoelectric tactile sensor array (4 × 4) is assembled on a spherical surface for mimicking robot fingers and an on-site thin-film sensor on the wing of an aircraft model to monitor the vibration in real-time during flight. The FTS film deposition offers a highly promising methodology for the application of functional thin-film from micro- to marcoscale devices, regardless of conformal problems.

The Clinical and Prognostic Characteristics of Primary Salivary Gland-Type Carcinoma in the Lung: A Population-Based Study.

This study aimed to explore the clinical and prognostic characteristics of primary salivary gland-type carcinoma (SGC). The entire cohort from the Surveillance, Epidemiology, and End Results database was used to calculate the SGC proportion. In total, 253,096 eligible patients, including 165,715 adenocarcinomas (ADCs), 87,062 squamous cell carcinomas (SCCs), and 319 SGCs, were selected to perform survival analyses. The data of 42 SGC patients from our hospital showed postoperative survival. Overall survival (OS) curves for different histological and surgical types were presented. The proportion of primary SGCs was 0.8 per 1000 patients. Patients with age ≤ 64 years old had a much higher proportion of SGC than those patients with age >64 years old. After adjusting for other confounders, among ADCs, SCCs, and SGC, SGCs had the best prognosis (HR 0.361, p < 0.001). Moreover, the 5-year OS rates of SGC patients were 55% and 7% in the group with surgery or without surgery, respectively (p < 0.001). The data of 42 patients from our hospital also showed a good survival of SGCs. Lobectomy improved the survival of SGCs significantly (adjusted HR 0.439, p = 0.016). In conclusion, pulmonary SGCs had the best prognosis among ADCs, SCCs, and SGCs. In addition, lobectomy could further improve the prognostic outcomes of SGCs.

Interactions Between Immunomodulatory Biomaterials and Immune Microenvironment: Cues for Immunomodulation Strategies in Tissue Repair.

The foreign body response (FBR) caused by biomaterials can essentially be understood as the interaction between the immune microenvironment and biomaterials, which has severely impeded the application of biomaterials in tissue repair. This concrete interaction occurs via cells and bioactive substances, such as proteins and nucleic acids. These cellular and molecular interactions provide important cues for determining which element to incorporate into immunomodulatory biomaterials (IMBs), and IMBs can thus be endowed with the ability to modulate the FBR and repair damaged tissue. In terms of cellular, IMBs are modified to modulate functions of immune cells, such as macrophages and mast cells. In terms of bioactive substances, proteins and nucleic acids are delivered to influence the immune microenvironment. Meanwhile, IMBs are designed with high affinity for spatial targets and the ability to self-adapt over time, which allows for more efficient and intelligent tissue repair. Hence, IMB may achieve the perfect functional integration in the host, representing a breakthrough in tissue repair and regeneration medicine.

The Difference and Significance of Parietal Pleura Invasion and Rib Invasion in Pathological T Classification With Non-Small Cell Lung Cancer.

Objective: This study was to explore the difference and significance of parietal pleura invasion and rib invasion in pathological T classification with non-small cell lung cancer. Methods: A total of 8681 patients after lung resection were selected to perform analyses. Multivariable Cox analysis was used to identify the mortality differences in patients between parietal pleura invasion and rib invasion. Eligible patients with chest wall invasion were re-categorized according to the prognosis. Cancer-specific survival curves for different pathological T (pT) classifications were presented. Results: There were 466 patients considered parietal pleura invasion, and 237 patients served as rib invasion. Cases with rib invasion had poorer survival than those with the invasion of parietal pleura (adjusted hazard ratio [HR]= 1.627, P =0.004). In the cohort for parietal pleura invasion, patients with tumor size ≤5cm reached more satisfactory survival outcomes than patients with tumor size >5cm (unadjusted HR =1.598, P =0.006). However, there was no predictive difference in the cohort of rib invasion. The results of the multivariable analysis revealed that the mortality with parietal pleura invasion plus tumor size ≤5cm were similar to patients with classification pT3 (P =0.761), and patients for parietal pleura invasion plus tumor size >5cm and pT4 had no stratified survival outcome (P =0.809). Patients identified as rib invasion had a poorer prognosis than patients for pT4 (P =0.037). Conclusions: Rib invasion has a poorer prognosis than pT4. Patients with parietal pleura invasion and tumor size with 5.1-7.0cm could be appropriately up-classified from pT3 to pT4.

Rapid microfluidic platform for screening and enrichment of cells secreting virus neutralizing antibodies.

As part of the body's immune response, antibodies (Abs) have the ability to neutralize pathogenic viruses to prevent infection. To screen for neutralizing Abs (nAbs) from the immune repertoire, multiple screening techniques have been developed. However, conventional methods have a trade-off between screening throughput and the ability to screen for nAbs via their functional efficacy. Although droplet microfluidic platforms have the ability to bridge this disparity, the majority of such reported platforms still rely on Ab-binding assays as a proxy for function, which results in irrelevant hits. Herein, we report the multi-module Droplet-based Platform for Effective Antibody RetrievaL (DROP-PEARL) platform, which can achieve high-throughput enrichment of Ab-secreting cells (ASCs) based on the neutralizing activity of secreted nAbs against the a target virus. In this study, in-droplet Chikungunya virus (CHIKV) infection of host cells and neutralization was demonstrated via sequential delivery of viruses and host cells via picoinjection. In addition, we demonstrate the ability of the sorting system to accurately discriminate and isolate uninfected droplets from a mixed population of droplets at a rate of 150 000 cells per hour. As a proof of concept, a single-cell neutralization assay was performed on two populations of cells (nAb-producing and non-Ab producing cells), and up to 2.75-fold enrichment of ASCs was demonstrated. Finally, we demonstrated that DROP-PEARL is able to achieve similar enrichment for low frequency (∼2%) functional nAb-producing cells in a background of excess cells secreting irrelevant antibodies, highlighting its potential prospect as a first round enrichment platform for functional ASCs. We envision that the DROP-PEARL platform could potentially be used to accelerate the discovery of nAbs against other pathogenic viral targets, and we believe it will be a useful in the ongoing fight against biological threats.