Size Control Research Articles

Size and shape control of microgel-encapsulating tumor spheroid via a user-friendly solenoid valve-based sorter and its application on precise drug testing

The precision of previous cancer research based on tumor spheroids, especially the microgel-encapsulating tumor spheroids, was limited by the high heterogeneity in the tumor spheroid size and shape. Here, we reported a user-friendly solenoid valve-based sorter to reduce this heterogeneity. The artificial intelligence algorithm was employed to detect and segmentate the tumor spheroids in real-time for the size and shape calculation. A simple off-chip solenoid valve-based sorting actuation module was proposed to sort out target tumor spheroids with the desired size and shape. Utilizing the developed sorter, we successfully uncovered the drug response variations on cisplatin of lung tumor spheroids in the same population but with different sizes and shapes. Moreover, with this sorter, the precision of drug testing on the spheroid population level was improved to a level comparable to the precise but complex single spheroid analysis. The developed sorter also exhibits significant potential for organoid morphology and sorting for precision medicine research.

Genome-wide association studies of body size traits in Tibetan sheep

BackgroundElucidating the genetic variation underlying phenotypic diversity will facilitate improving production performance in livestock species. The Tibetan sheep breed in China holds significant historical importance, serving as a fundamental pillar of Qinghai’s animal husbandry sector. The Plateau-type Tibetan sheep, comprising 90% of the province’s population, are characterized by their tall stature and serve as the primary breed among Tibetan sheep. In contrast, Zhashijia sheep exhibit larger size and superior meat quality. These two species provide an excellent model for elucidating the genetic basis of body size variation. Therefore, this study aims to conduct a comprehensive genome-wide association study on these two Tibetan sheep breeds to identify single nucleotide polymorphism loci and regulatory genes that influence body size traits in Tibetan sheep.ResultIn this study, the phenotypic traits of body weight, body length, body height, chest circumference, chest depth, chest width, waist angle width, and pipe circumference were evaluated in two Tibetan sheep breeds: Plateau-type sheep and Zhashijia Tibetan sheep. Whole genome sequencing generated 48,215,130 high-quality SNPs for genome-wide association study. Four methods were applied and identified 623 SNPs significantly associated with body size traits. The significantly associated single nucleotide polymorphisms identified in this study are located near or within 111 candidate genes. These genes exhibit enrichment in the cAMP and Rap1 signaling pathways, significantly affecting animal growth, and body size. Specifically, the following genes were associated: ASAP1, CDK6, FRYL, NAV2, PTPRM, GPC6, PTPRG, KANK1, NTRK2 and ADCY8.ConclusionBy genome-wide association study, we identified 16 SNPs and 10 candidate genes associated with body size traits in Tibetan sheep, which hold potential for application in genomic selection breeding programs in sheep. Identifying these candidate genes will establish a solid foundation for applying molecular marker-assisted selection in sheep breeding and improve our understanding of body size control in farmed animals.

Application of deep learning methods for beam size control during user operation at the Advanced Light Source

Past research at the Advanced Light Source (ALS) provided a proof-of-principle demonstration that deep learning methods could be effectively employed to compensate for the significant perturbations to the transverse electron beam size induced by user-controlled adjustments of the insertion devices. However, incorporating these methods into the ALS’ daily operations has faced notable challenges. The complexity of the system’s operational requirements and the significant upkeep demands has restricted their sustained application during user operation. Here, we introduce the development of a more robust neural network (NN)-based algorithm that utilizes a novel online fine-tuning approach and its systematic integration into the day-to-day machine operations. Our analysis emphasizes the process of NN model selection, demonstrates the superior performance of the NN-based method over traditional feedback methods, and examines the effectiveness and resilience of the new algorithm during user-operation scenarios. Published by the American Physical Society 2024

Size Uniformity of CsPbBr3 Perovskite Quantum Dots via Manganese-Doping.

The achievement of size uniformity and monodispersity in perovskite quantum dots (QDs) requires the implementation of precise temperature control and the establishment of optimal reaction conditions. Nevertheless, the accurate control of a range of reaction variables represents a considerable challenge. This study addresses the aforementioned challenge by employing manganese (Mn) doping to achieve size uniformity in CsPbBr3 perovskite QDs without the necessity for the precise control of the reaction conditions. By optimizing the Mn:Pb ratio, it is possible to successfully dope CsPbBr3 QDs with the appropriate concentrations of Mn²⁺ and achieve a uniform size distribution. The spectroscopic measurements on single QDs indicate that the appropriate Mn²⁺ concentrations can result in a narrower spectral linewidth, a longer photoluminescence (PL) lifetime, and a reduced biexciton Auger recombination rate, thus positively affecting the PL properties. This study not only simplifies the size control of perovskite QDs but also demonstrates the potential of Mn-doped CsPbBr3 QDs for narrow-linewidth light-emitting diode applications.

Tailoring particle size/morphology for the stable cathode performance of polygonal-shaped Li(Ni,Mn)2O4 single crystals

We regulate the particle size and crystallographic facet of single-crystal (SC) Li(Ni,Mn)2O4 (LNMO) cathode materials via flux-selective molten salt method. By simply adjusting Li2MoO4 or LiI as sintering aids, we synthesized size controlled SC particles, both small and large, and comparatively investigated their electrochemical behavior focusing on the lithiation/delithiation reactivity in conjunction with the particle size and surface planes. Considering the growth mechanism of a SC particles with a specific crystal plane, such particle size control is not determined solely by the synthetic condition but must also consider the interfacial energy of the crystal planes in conjunction with the fluxes what we used. While the initial charge capacity is similar, the given cathode using a small SC LNMO (using LiI) with uniform particle sizes (≤5 μm) exhibits outstanding rate capability with stable capacity retention under changing current density, which indicates stable lithium transport during the repetitive electrochemical reactions. The dependency of the impedance response with change in the electrode resistances as well as the stability during the cycle reactions in conjunction with the post-mortem Li distribution by using laser-induced breakdown spectroscopy as a function of porosity change and cell degradation are thoroughly discussed from the standpoint of regulated particle property.

Carboxymethylcellulose and rare earth metal cation self-assembly: Tunable encapsulation of carbon dots in a multifunctional transparent film

Due to their unique properties, carbon dots have attracted significant interest across diverse fields. However, obstacles such as uneven size distribution in the course of synthesis and excessive aggregation lead to fluorescence quenching during solidification process. Moreover, conventional doping procedures frequently yield carbon dot films with constrained functionality, inferior durability, and harsh environments, thereby restricting their practical applications. To address these issues, this study fabricates N-doped carbon dots via a straightforward hydrothermal approach and incorporates them into CMC films by metathesis with CeCl3·7H2O, resulting in a unique carbon dot-encapsulated film. This film overcomes the problem of fluorescence quenching caused by excessive aggregation of carbon dots and allows for size control by adjusting the concentration of Ce(III). The resulting film achieves extreme transparency and superior performance compared to existing UV-blocking films. In addition, the film exhibits exceptional resistance to acids and bases, bleaching, excellent mechanical properties, and good thermal and water stability. Based on these properties, the film achieves size-controlled in-situ photoluminescence, full UV shielding, Cu2+ ion detection, anti-counterfeiting, and information encryption. The water-processable and water-adhesive characteristics of CMC enable its use in real-life situations, opening the door to wider use of solid-state carbon dots for multifunctional and intelligent applications.

Preparation and size control of epoxy resin multilevel structures with SiO2 particles

In the process of preparing porous epoxy materials using reaction-induced phase separation (RIPS), the introduction of an appropriate amount of SiO2 particles enables the control of the phase separation behavior of the system and its ultimate phase structure. This study examined the role of SiO2 particles in the preparation and size control of epoxy resin multilevel structures by analyzing the phase separation and reaction kinetics in an epoxy resin blend system and characterizing the ultimate phase structure. It was found that fumed SiO2 particles (0–3 wt%) added to the DGEBA/DDCM/PEG200 blends resulted in significant interfacial stabilization, delaying phase separation. With an increase in the fumed SiO2 particle content, the phase structure stopped evolving at an earlier stage of phase separation. In addition, the fumed SiO2 particles dispersed in the porogen-enriched phase helped to stabilize the system, i.e., preventing or slowing down the segregation and aggregation of the components in the system, which may inhibit secondary phase separation in the porogen-enriched phase. When 350 nm SiO2 particles were used, an increase in the particle size resulted in a larger phase structure. The SiO2 particles were dispersed within the pore-forming agent phase, increasing the proportion of the pore-forming agent and exerting an occupancy effect, which diminished with decreasing SiO2 particle size and increasing hydrophobicity. Notably, the surface of the epoxy porous material skeleton was decorated with small pits formed by the acid etching of the SiO2 particles, and this multilevel structure contributed to the specific surface area. The multilevel structure can be precisely controlled by adjusting the size, content, and wettability of the SiO2 particles. The results of this study are universal and instructive for the preparation of porous materials using a phase separation method in combination with solid particles.

Parameter ESTimation With the Gauss-Levenberg-Marquardt Algorithm: AnIntuitive Guide.

In this paper, we review the derivation of the Gauss-Levenberg-Marquardt (GLM) algorithm and its extension to ensemble parameter estimation. We explore the use of graphical methods to provide insights into how the algorithm works in practice and discuss the implications of both algorithm tuning parameters and objective function construction in performance. Some insights include understanding the control of both parameter trajectory and step size for GLM as a function of tuning parameters. Furthermore, for the iterative Ensemble Smoother (iES), we discuss the importance of noise on observations and show how iES can cope with non-unique outcomes based on objective function construction. These insights are valuable for modelers using PEST, PEST++, or similar parameter estimation tools.

In-situ wet milling for particle size control in continuous crystallization: Expanding the attainable region

Continuous mixed-suspension mixed-product removal crystallizer cascades are robust and proven options for continuous manufacturing. However, when applied to a late-stage drug substance the desired particle size could not be achieved due to rapid crystal growth and slow secondary nucleation kinetics. This necessitated a batch terminal milling operation to achieve particle size control (Johnson et al., 2021). To overcome this and to intensify the process, an in-situ high-shear wet mill was integrated into the continuous equipment train to achieve the target physical properties of the drug substance that met the quality and manufacturability criteria needed for the drug product. This article describes the workflow used to optimize the equipment set and operational parameters. Incorporation of a high-shear wet mill operated intermittently in the continuous drug substance process greatly expanded the attainable particle size region, improved product quality, reduced cycle time, and simplified process development and scale-up compared to the process of batch milling after continuous crystallization. Small scale batch milling experiments were used to characterize milling performance at lab and production scales and inform operational space. Several lab-scale continuous runs were then used to define the process operating space and validate the process parameters necessary to meet the particle specifications of the product. Scale-up of the equipment set for in-situ milling was also demonstrated. This approach was tested at lab-scale on representative material operating for 70 h while changing the particle size of the product in real time. This illustrated the potential of intermittent milling for model-free particle size control.

An epidemiological investigation into the reasons for high bovine tuberculosis incidence in cattle herds of the Burren, Ireland, prior to 2020

Herd-level bovine tuberculosis (bTB) incidence was examined in the Burren, an area in the west of Ireland where herd owners practice distinctive transhumance practices, with upland winter grazing. Prior to the initiation of our study in 2020, bTB incidence had for many years been unusually high in the Burren in comparison with the rest of the country, although the most recent figures have come down to being closer to the national average. Using data from the period prior to 2020, we mapped bTB infection in Burren herds alongside a range of indicators thought to have an association with it - herd size, herd density, herd type, cattle movement, and badger (Meles meles) population and control data, as well as rainfall and altitude. We also looked at how summary statistics for these variables differed when Burren herds with a history of bTB were compared to other Burren herds, as well as bTB positive and negative herds from outside the Burren. We found that for many indicators Burren herds would be expected to be low risk when compared to other herds in Ireland. An exception to this was for rainfall: hot spot areas for bTB in the Burren were found in areas of higher rainfall, on average herds in the Burren experienced more rainfall than those outside it, and bTB herds in the Burren experienced higher rainfall than non-bTB herds. Separately, for Burren herds only, a logistic regression model was developed to explain bTB breakdown occurrence using a matched case-control approach. Cases were herds which had experienced a new bTB breakdown between 2015 and 2019 (n = 260) and these were matched on herd type and herd size with the same number of herds not experiencing a breakdown during this period. This showed that, of a range of exogenous variables, rainfall was the most strongly associated with herd-level bTB incidence. These results suggest that high levels of exposure to inclement weather, and/or better environmental survival of Mycobacterium bovis in the environment, may contribute to high bTB rates in the Burren. However, as rainfall showed a highly aggregated distribution, this relationship may be due to an unmeasured factor correlated with it. Mapping and graphical output suggested that, although herd sizes in the Burren were on average lower than nationally, within the Burren they were higher in areas of higher prevalence, suggesting that mechanisms associated with herd size, such as increased contacts between and within herd, and with wildlife, may also play a role.

Two-sample test for high-dimensional covariance matrices: A normal-reference approach

Testing the equality of the covariance matrices of two high-dimensional samples is a fundamental inference problem in statistics. Several tests have been proposed but they are either too liberal or too conservative when the required assumptions are not satisfied which attests that they are not always applicable in real data analysis. To overcome this difficulty, a normal-reference test is proposed and studied in this paper. It is shown that under some regularity conditions and the null hypothesis, the proposed test statistic and a chi-squared-type mixture have the same limiting distribution. It is then justified to approximate the null distribution of the proposed test statistic using that of the chi-squared-type mixture. The distribution of the chi-squared-type mixture can be well approximated using a three-cumulant matched chi-squared-approximation with its approximation parameters consistently estimated from the data. The asymptotic power of the proposed test under a local alternative is also established. Simulation studies and a real data example demonstrate that the proposed test works well in general scenarios and outperforms the existing competitors substantially in terms of size control.

Control of the size distribution of AuNPs for colorimetric sensing by pulsed laser ablation in liquids

Gold nanoparticles (AuNPs) are extensively employed in colorimetric sensing, taking advantage of their optical properties to detect variables via observable color changes. These properties are primarily driven by localized surface plasmon resonance (LSPR), particularly pronounced in AuNPs within the visible spectrum. In this study, AuNPs were synthesized via pulsed laser ablation in liquids (PLAL) with a laser pulse energy (Ep) ranging from 25 mJ to 75 mJ. Size distributions, hydrodynamic diameters, polydispersity indices (PDI), absorbance intensity, and LSPR were characterized. Spherical AuNPs with FCC structure were synthesized, exhibiting a maximum absorption peak centered at approximately 529 nm wavelength and a size range between 50 nm and 178 nm, easily adjustable depending on the laser pulse energy used in the synthesis process. An anomalous behavior was noted at Ep=50 mJ, exhibiting three peaks in size distribution, high PDI, low absorbance intensity, and indistinct LSPR. By extending the ablation time from 10 min to 30 min, particle size decreased alongside lower PDI. Size distributions transitioned from three to two peaks, absorbance increased, and LSPR became readily identifiable. These findings underscore the size control over AuNP characteristics achievable through PLAL synthesis parameters, promising significant implications for the optimization of colorimetric sensor design and development.

The Basics of Evolution Strategies: The Implementation of the Biomimetic Optimization Method in Educational Modules.

With a focus on education and teaching, we provide general background information on bioinspired optimization methods by comparing the concept of optimization and the search for an optimum in engineering and biology. We introduce both the principles of Darwinian evolution and the basic evolutionary optimization procedure of evolution strategies. We provide three educational modules in work sheets that can be used by teachers and students to improve their understanding of evolution strategies. The educational module "Optimization of a Milk Carton" shows that the material consumption in producing a milk carton can be minimized using an evolution strategy with a mutative step size control. The use of a standard dice and a pocket calculator enables new milk cartons to be generated, with the offspring having the lowest material consumption becoming the parent of the next generation. The other educational modules deal with the so-called brachistochrone problem. The module "Fastest and Shortest Marble Track" provides a construction plan for a marble track whereby students can experimentally compare the "path of shortest length" with the "path of shortest time". The EvoBrach software, is used in the module "Various Marble Track Shapes" to compare the running times of a marble on a straight line, a parabola, and a brachistochrone. In conclusion, the introduction to the biomimetic method of evolution strategies and the educational modules should deepen the understanding of both optimization problems and biological evolution.

Cell Membrane-Derived Nanoparticles as Biomimetic Nanotherapeutics to Alleviate Fatty Liver Disease.

The prevalence of metabolic dysfunction associated-steatotic liver disease (MASLD) (formerly known as nonalcoholic fatty liver disease; NAFLD) is estimated at around 32% of the world's population, resulting in a major healthcare concern in recent times. Current pharmaceutical methods lack efficacy for the treatment of the disease because of suboptimal pharmacokinetic parameters including poor bioavailability, short half-life, and premature clearance. Designing an efficient drug delivery system that provides a protective environment is critical for addressing these challenges. Such a system should aim to enhance the cellular uptake of drugs, improve their bioavailability, and reduce the chances of rapid clearance. Here, we developed nanoengineered natural cell membrane-derived nanoparticles (CMNs) incorporated with a model drug, rosuvastatin, in the bilayer assembly of CMNs to reduce the accumulation of lipids in hepatocytes, a hallmark of MASLD. We used a cell extrusion technique to develop self-assembled CMNs with precise size control compared to the cell shearing method. Interestingly, the prepared CMNs were found to be nonphagocytic, representing around 1.13% of phosphatidylserine receptors on healthy cells, which allows the possibility of their use as stealth nanoparticles for drug delivery. Furthermore, CMNs exhibit higher drug-loading efficiency, excellent cytocompatibility, and enhanced cellular internalization capabilities. Moreover, we show that the delivery of rosuvastatin-loaded CMNs in the in vitro MASLD model efficiently reduced hepatocyte lipid accumulation, including total cholesterol (26.8 ± 3.1%) and triglycerides (11.8 ± 0.8%), compared to the negative control. Taken together, the nanoengineered biomimetic CMNs enhance the drug's bioactivity in hepatic cells, establishing a foundation for further investigation of this drug delivery system in treating MASLD.

A novel strategy to regulate the precipitation-strengthened high-entropy alloy fabricated by laser directed energy deposition

The optimization of the aging process is an effective strategy for achieving excellent performance in the rapidly solidified CoCrFeNiTi0.7 high-entropy alloy (HEA). Current research has clearly demonstrated that the unique design of the high-low duplex aging (HLDA) strategy plays a crucial role in achieving outstanding wear resistance in additive manufacturing of the rapidly solidified CoCrFeNiTi0.7 HEA. The microhardness of the SA-750 and HLDA samples increased to approximately 678 HV and 729 HV, respectively, compared to the as-deposited sample (LDED) with a microhardness of approximately 506 HV. Additionally, the wear rates of the SA-750 and HLDA samples were reduced by approximately 17.1% and 24.7%, respectively, compared to the LDED sample. This remarkable improvement in wear resistance can be attributed to the introduction of high-density nanoscale core-shell microstructures formed by secondary η2 and L12-γ' phases. Furthermore, when compared to the grain size of SA-750 (65.63 μm), the HLDA sample exhibited the precipitation of cellular precipitates at the grain boundary, and the grain size (68.46 μm) did not show significant growth or coarsening. This demonstrates the precise control of the matrix grain size achieved in our study. Therefore, the high-low duplex aging treatment has been validated for developing high-performance rapidly solidified CoCrFeNiTi0.7 HEA. This strategy provides a targeted approach for tissue design to tap into the maximum potential of additive manufacturing precipitation-strengthened HEAs.

Internal Audit to Monitor the Injected Activity in PET/CT Using Control Charts.

In an effort to limit the risks associated with medical radiation exposure, the last century witnessed the development of dose control mechanisms, recommended by the International Commission on Radiological Protection. This organization recommends the optimization of radiation protection to provide the highest level of safety that may reasonably be achievable. Adhering to the "as low as reasonably achievable" principle, the purpose of this study was to monitor the 18F-FDG injected activity in PET and optimize the radiation protection through an internal audit process. This monitoring allows the identification of opportunities for improvement in patient care and safety, as well as to establish a periodic review of the medical unit reference levels. The methodology is based on short run Quesenberry (Q) statistics and normalized nonconstant sample size (Z-chart) control charts. Anonymized data from 512 patients were selected from a set of 18F-FDG PET/CT (Siemens, Biograph 6) examinations performed during 10 months. The analyzed variable was the ratio between the 18F-FDG injected activity (MBq) and patient weight (kg). Mean injected 18F-FDG activity was 347.811 ± 64.967 MBq corresponding to a mean effective dose of 6.608 ± 1.234 mSv. The ratio between the 18F-FDG injected activity and the body mass of patients was reduced from 5.243 ± 0.716 to 5.171 ± 0.672 MBq/kg during the statistical data analysis. The study demonstrates that control charts can be a useful tool to signal situations where patients receive an activity significantly different from the standard practice in a medical unit. The use of joint control charts is a suitable tool for detecting nonoptimized radiopharmaceutical administration. This analysis provides opportunities to evaluate and improve the quality of practice in nuclear medicine. This methodology constitutes an internal audit that may help health care professionals to make appropriate decisions to ensure all patients receive the safest and most appropriate care.

Accelerating Anhydrous Proton Transport in Covalent Organic Frameworks: Pore Chemistry and its Impacts

AbstractProton conduction is important in both fundamental research and technological development. Here we report designed synthesis of crystalline porous covalent organic frameworks as a new platform for high‐rate anhydrous proton conduction. By developing nanochannels with different topologies as proton pathways and loading neat phosphoric acid to construct robust proton carrier networks in the pores, we found that pore topology is crucial for proton conduction. Its effect on increasing proton conductivity is in an exponential mode other than linear fashion, endowing the materials with exceptional proton conductivities exceeding 10−2 S cm−1 over a broad range of temperature and a low activation energy barrier down to 0.24 eV. Remarkably, the pore size controls conduction mechanism, where mesopores promote proton conduction via a fast‐hopping mechanism, while micropores follow a sluggish vehicle process. Notably, decreasing phosphoric acid loading content drastically reduces proton conductivity and greatly increases activation energy barrier, emphasizing the pivotal role of well‐developed proton carrier network in proton transport. These findings and insights unveil a new general and transformative guidance for designing porous framework materials and systems for high‐rate ion conduction, energy storage, and energy conversion.

Accelerating Anhydrous Proton Transport in Covalent Organic Frameworks: Pore Chemistry and its Impacts.

Proton conduction is important in both fundamental research and technological development. Here we report designed synthesis of crystalline porous covalent organic frameworks as a new platform for high-rate anhydrous proton conduction. By developing nanochannels with different topologies as proton pathways and loading neat phosphoric acid to construct robust proton carrier networks in the pores, we found that pore topology is crucial for proton conduction. Its effect on increasing proton conductivity is in an exponential mode other than linear fashion, endowing the materials with exceptional proton conductivities exceeding 10-2 S cm-1 over a broad range of temperature and a low activation energy barrier down to 0.24 eV. Remarkably, the pore size controls conduction mechanism, where mesopores promote proton conduction via a fast-hopping mechanism, while micropores follow a sluggish vehicle process. Notably, decreasing phosphoric acid loading content drastically reduces proton conductivity and greatly increases activation energy barrier, emphasizing the pivotal role of well-developed proton carrier network in proton transport. These findings and insights unveil a new general and transformative guidance for designing porous framework materials and systems for high-rate ion conduction, energy storage, and energy conversion.

Metabolic, transcriptomic, and genetic analyses of candidate genes for seed size in watermelon.

Seed size (SS) constitutes a pivotal trait in watermelon breeding. In this study, we present findings from an examination of two watermelon accessions, namely, BW85 and F211. Seeds from BW85 exhibited a significant enlargement compared to those of F211 at 13 days after pollination (DAP), with the maximal disparity in seed length and width manifesting at 17 DAP. A comprehensive study involving both metabolic and transcriptomic analyses indicated a significant enrichment of the ubiquinone and other terpenoid-quinone biosynthesis KEGG pathways. To detect the genetic region governing seed size, a BSA-seq analysis was conducted utilizing the F2 (BW85 × F211) population, which resulted in the identification of two adjacent QTLs, namely, SS6.1 and SS6.2, located on chromosomes 6. SS6.1 spanned from Chr06:4847169 to Chr06:5163486, encompassing 33 genes, while SS6.2 ranged from Chr06:5379337 to Chr06:5419136, which included only one gene. Among these genes, 11 exhibited a significant differential expression between BW85 and F211 according to transcriptomic analysis. Notably, three genes (Cla97C06G113960, Cla97C06G114180, and Cla97C06G114000) presented a differential expression at both 13 and 17 DAP. Through annotation, Cla97C06G113960 was identified as a ubiquitin-conjugating enzyme E2, playing a role in the ubiquitin pathway that mediates seed size control. Taken together, our results provide a novel candidate gene influencing the seed size in watermelon, shedding light on the mechanism underlying seed development.

Full-cycle study on developing a novel structured micromixer and evaluating the nanoparticle products as mRNA delivery carriers

Achieving precise control of nanoparticle size while maintaining consistency and high uniformity is of paramount importance for improving the efficacy of nanoparticle-based therapies and minimizing potential side effects. Although microfluidic technologies are widely used for reliable nanoparticle synthesis, they face challenges in meeting critical homogeneity requirements, mainly due to imperfect mixing efficiency. Furthermore, channel clogging during continuous operation presents a significant obstacle in terms of quality control, as it progressively impedes the mixing behavior necessary for consistent nanoparticle production for therapeutic delivery and complicates the scaling-up process. This study entailed the development of a 3D-printed novel micromixer embedded with hemispherical baffle microstructures, a dual vortex mixer (DVM), which integrates Dean vortices to generate two symmetrical counter-rotating intensified secondary flows. The DVM with a relatively large mixer volume showed rapid mixing characteristics even at a flow rate of several mL min−1 and produced highly uniform lipids, liposomes, and polymer nanoparticles in a size range (50–130 nm) and polydispersity index (PDI) values below 0.15. For the evaluation of products, SARS-CoV-2 Spike mRNA-loaded lipid nanoparticles were examined to verify protein expression in vitro and in vivo using firefly luciferase (FLuc) mRNA. This showed that the performance of the system is comparable to that of a commercial toroidal mixer. Moreover, the vigorous in-situ dispersion of nanoparticles by harnessing the power of vortex physically minimizes the occurrence of aggregation, ensuring consistent production performance without internal clogging of a half-day operation and facilitating quality control of the nanoparticles at desired scales.