Nanostructured surfaces that reproduce the topography of biological templates are of growing interest for wetting control, optical management and mechano-bactericidal applications, but systematic study of these topography–function relationships requires fabrication routes that replicate the biological spatial arrangement with quantified fidelity. Here we establish a surface fabrication methodology that converts a scanning electron micrograph of a biological surface directly into an electron-beam lithography (EBL) exposure pattern, implemented as the open-source SEM2DXF workflow, and demonstrate it on cicada (Cicada sp.) wing nanopillars imaged at ×19,000 and ×50,000 magnification. Pillar centroids are detected automatically, truncated boundary features are completed by ellipse fitting, and each pillar is exported as a closed-polygon entity; because vector EBL systems expose closed polygons by area fill, this reduces the number of explicitly addressed beam positions ~8.7-fold, consistent with the ~8-fold write-time reduction measured with the pattern generator estimator. Applied to ×50,000-derived patterns (D = 115 nm, pitch = 155 nm), PMMA nanopillar surfaces were fabricated across 16 area doses (200–700 µC cm−2) and characterised by SEM and AFM. A sigmoidal dose–height relationship defines a three-dimensional process window (380–490 µC cm−2) that simultaneously optimises pillar diameter, height (~200 nm) and aspect ratio relative to the cicada reference. Pillar-by-pillar registration against the biological template (N = 1,174 interior pairs) gives a median positional mismatch of 32 nm, less than half the nearest-neighbour pitch, with a mean systematic displacement of (−8, +2) nm, the first quantitative spatial fidelity benchmark for a directly SEM-derived EBL surface. The fabricated pillars are cylindrical (top ≈ base ≈ 100–110 nm) rather than conical (cicada base ~130 nm, top ~50 nm), an intrinsic consequence of positive-tone resist development that we discuss in relation to etch-transfer strategies for functional surfaces.
The concept and feasibility of producing liposomes by rehydrating engineered lipid nanoconstructs are demonstrated in this study. Nanoconstructs of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) were produced using a microfluidic delivery probe integrated with an atomic force microscope. The subsequent rehydration of these POPC constructs led to the formation of liposomes, most of which remained adhered to the surface. The size (e.g., diameter) of the liposomes could be tuned by varying the lateral dimension of the lipid constructs. Hierarchical liposomal structures, such as pentagons containing five liposomes at the corners, could also be designed and produced by depositing lipid constructs to designated locations on the surfaces, followed by rehydration. This new means allows for regulating liposomal sizes, distributions, and compositions. The outcomes benefit applications of liposomes as delivery vehicles, sensors, and building blocks in biomaterials design. The ability to produce hierarchical liposomal structures benefits numerous applications such as proto-cell development, multiplexed bio-composite materials, and the engineering of local bio-environments.
Biosensors, while holding immense promise for biomarker detection, face substantial challenges in analytical performance, fabrication intricacies, and complex applications, hindering their seamless integration into point-of-care (POC) settings. Metamaterial-based plasmonic biosensors offer tremendous potential for biomarker detection; however, their widespread adoption in POC diagnostics remains hampered by limitations in sensitivity, fabrication complexity, and production cost. Herein, we introduce, for the first time, in situ-controlled spatial designs on metamaterial-based plasmonic sensors, demonstrating unprecedented sensitivity in detecting extracellular vesicles (EVs). In the fabrication process, commercially available optical disks were repurposed as nanostructured substrates, yielding a cost reduction of up to 260-fold ($0.90 per sensor) and a fabrication time reduction of approximately 960-fold, compared to conventional e-beam lithography. Leveraging inherent nanogratings, measurements are conducted on a compact, palm-sized platform, addressing challenges in usability and portability associated with bulky optical designs. Through ex situ immobilization of gold nanoparticles (AuNPs) or in situ formation of nanoislands (NIs), we have engineered plasmonic hotspots that substantially enhanced local electric field intensities, thereby amplifying the bulk refractive index sensitivity of the sensors. Finite-difference time-domain simulations confirmed that the spatial arrangement and interparticle distances of spatial designs enhance near-field effects. The optimized platform exhibits up to a 5.5-fold enhancement in refractive index sensitivity. Moreover, based on data obtained from nanoparticle tracking analysis (NTA), fluorescence-enhanced NTA (fNTA), and recent literature benchmarks, the platform demonstrated detection limits of 104 particles/μL (as determined by raw NTA measurements), approximately 330 fg/μL (estimated via literature-based EV mass calculations), and 138 EVs/μL (quantified via fNTA using marker-specific labeling). Herein, we anticipate that repurposing disks as metamaterial sensors has the potential to address pressing challenges in usability, portability, cost, and complexity. Besides, 3D configurations on sensors would improve the analytical performance, offering highly sensitive and facile platforms for diverse applications in the future.
Microparticle production system utilizing a microfabricated nozzle array and piezoelectric technology enables precise and scalable polymeric microparticle production, offering significant improvements in drug delivery systems.
The constructs of lipid molecules follow self-assembly, driven by intermolecular interactions, forming stacking of lipid bilayer films. Achieving designed geometry at nano- to micro-levels with packing deviating from the near-equilibrium structure is difficult to achieve due to the strong tendency of lipid molecules to self-assemble. Using ultrasmall (<fL) droplets containing designed molecules, our prior work has demonstrated that molecular assembly, in principle, is governed mainly by transient inter-molecular interactions under their dynamic spatial confinement, i.e., tri-phase boundaries during drying. As a result, the assemblies can deviate, sometimes significantly, from the near-equilibrium structures of self-assembly. The present work applies the approach and concept to lipid molecules using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). Taking advantage of the high spatial precision and the minute size of the delivery probe in our combined atomic force microscopy and microfluidic delivery, the transient shape of each liquid droplet is regulated. In doing so, the final geometry of the POPC assemblies has been regulated to the designed geometry with nanometer precision. The results extend the concept of controlled assembly of molecules to amphiphilic systems. The outcomes exhibit high potential in lipid-based biomaterial science and biodevice engineering.
Alginate hydrogels are frequently used in 3D bioprinting and tissue repair and regeneration. Establishing the structure-property-performance correlation of these materials would benefit significantly from high-resolution structural characterization in aqueous environments from the molecular level to continuum. This study overcomes technical challenges and enables high-resolution atomic force microscopy (AFM) imaging of hydrated alginate hydrogels in aqueous media. By combining a new sample preparation protocol with extremely gentle tapping mode AFM imaging, we characterized the morphology and regional mechanical properties of the hydrated alginate. Upon cross-linking, basic units of these hydrogel materials consist of egg-box dimers, which assemble into long fibrils. These fibrils congregate and pile up, forming a sponge-like structure, whose pore size and distribution depend on the cross-linking conditions. At the exterior, surface tension impacts the piling of fibrils, leading to stripe-like features. These structural features contribute to local, regional, and macroscopic mechanics. The outcome provides new insights into its structural characteristics from nanometers to tens of micrometers, i.e., at the dimensions pertaining to biomaterial and hydrogel-cell interactions. Collectively, the results advance our knowledge of the structure and mechanics from the nanometer to continuum, facilitating advanced applications in hydrogel biomaterials.
Soft materials, such as polymers, gels, biomaterials, and elastomers, have unique mechanical properties. Micro/nanoindentation techniques allow for the characterization of mechanical parameters. Understanding these properties is essential for designing and optimizing soft materials for specific applications. In this study, it is aimed to develop a low-cost and easy-to-use microindenter that can enable to measure the local mechanical properties of soft samples. Micro/nanoindentation with atomic force microscope (AFM) has advantages, such as high sensitivity and measurement capability of local mechanical properties. However, it has some disadvantages, such as being difficult to use, requiring a trained specialist, and high consumable costs. In this study, it is intended to inherit the advantages of AFM-based indentation technique and overcome its limitations. We designed robust and low-cost metal cantilevers for the force measurement. A low-cost voice coil motor is used as force actuators. An optical slot sensor is employed to measure the cantilever deflection without the need for laser and photodetector adjustment as in AFMs. In the study, 5:1 and 25:1 PDMS samples were prepared to test the apparatus. The elastic modulus for the PDMS 5:1 and 25:1 samples was measured as 3.72 +/- 0.05 MPa and 0.96 +/- 0.15 MPa.
As the number of UAVs (Unmanned Aerial Vehicles) and the market size have been expanding rapidly in recent years, projects such as NextGen and SESAR aim to include UAVs in air traffic. Therefore, different perspectives on understanding flight patterns can contribute to more effective management of future air traffic. Analysis of flight data offers an important insight into the operations of a UAV. In this study, it is aimed to extract a flight fingerprint using different machine learning techniques by means of a public dataset and the data obtained from our experimental flights. To get the individual flight pattern, multidimensional UAV sensor data has been reduced using manifold learning methods. By comparison, the most proper manifold method that allows highest classification accuracy (CA) has been investigated. Their performances are compared using both different manifold types and different classification methods. Then, the obtained manifold is used as flight fingerprints and validated by classification techniques. Various unsupervised manifold learning techniques such as t-Distributed Stochastic Neighbor Embedding (t-SNE), Locally Linear Embedding (LLE), Isometric Feature Mapping (ISOMAP) were tried for dimension reduction. For flight fingerprint classification, supervised machine learning techniques such as k-Nearest Neighbors (k-NN), Adaboost, Neural Network, Bayes, etc., were tested. It has been observed that the highest classification accuracy is achieved with the t-SNE manifold and k-NN classification pair. The extracted fingerprint can find many application areas such as performance tests in production lines, air traffic control, risk analysis, anomaly detection, observing pilot performance, drone efficiency over time.
Forming a fundamental understanding of tribological processes on the atomic scale has the potential to revolutionize the control of friction and wear in macroscopic mechanical systems. On the other hand, methods such as atomic force microscopy (AFM) that provide nanoscale spatial resolution are severely limited in terms of scanning speed when compared with macroscopic mechanical processes, leading to a "speed gap" between fundamental and applied tribology that spans several orders of magnitude. Here, we propose a new method combining AFM experiments with simultaneous quartz crystal microbalance (QCM) measurements for high-speed nanoscale tribology. In particular, scanning speed and vibration amplitude are controlled by QCM whereas normal loads are controlled by AFM. Complementary data are simultaneously recorded in the form of nanoscale, two-dimensional maps of frequency shifts and lateral forces provided by the QCM and AFM, respectively. Proof-of-principle results are presented on a gold-coated QCM sensor surface patterned with a graphene array, whereby stick and partial slip regimes are observed as a function of sliding speed.
Extracting dynamic features of a cell plays important role in understanding cell response to internal or external perturbations, which can be both a painful and imprecise task as one makes it manually in ocular way. Instead of using complex methods, we introduce a simple approach that uses disparity maps for segmentation by means of sequential frame couples. In our approach, disparity maps provide three-dimensional clues that can be used for cell segmentation. One of the contributions of this work is to generate pseudo 3D cell database using cell video frame couples. In addition, the optical flow method is performed to understand the cell behaviour and local dynamic movements. A mask regional convolutional neural network (Mask R-CNN) approach that requires manual segmented dataset and long training time is used for comparison. Obtained disparity-based segmentation and optical flow data are blended to easily analyse and evaluate the cell motility and mobility. In order to validate the segmentation results, Jaccard similarity index method is applied. Consequently, we succeed in dynamic segmentation-based tracking for understanding the cell behaviour without video enhancement or preprocessing steps, such as colour adjustment, filtering, thresholding.
Nano iğnelerin üretimi, yüksek performanslı çok işlevli nano cihazların geliştirilmesinde artan endüstriyel taleplerden dolayı ilgi çekmektedir. Nano ölçekli uçlar kontrollü transdermal ilaç salımı, soğuk katot alan emisyonu, taramalı uç mikroskobu, yansıma önleyici kaplama ve nanoindentasyon uygulamalarında yaygın olarak kullanılmaktadır. Taramalı uç mikroskobu ailesinin bir üyesi olan Atomik kuvvet mikroskobu (AKM), 1980'lerden beri yüksek çözünürlüklü yüzey karakterizasyonu için yaygın olarak kullanılan güçlü bir araç haline gelmiştir. AKM sensörü, esnek bir kuvvet algılayıcı konsoldan ve serbest ucunda nano ölçekli nanotipten oluşmaktadır. Yüksek çözünürlüklü AKM için nano-iğnenin eğrilik yarıçapı önem taşımaktadır. Islak aşındırma teknikleri ile AKM tip mikrofabrikasyonu düşük maliyet, kolay erişim ve (100) kristal düzleminde homojen aşındırma oranı gibi avantajları bulunmaktadır. Bu çalışmada, litografi ve ıslak aşındırma gibi mikrofabrikasyon teknikleri kullanılarak silisyum nano uçlar üretilmiştir. Yüksek sivrilik ve en boy oranlı uçlara sahip olacak şekilde süreç optimize edilmiştir. Anizotropik ıslak aşındırma için Potasyum Hidroksit (KOH) ve Tetrametil Amonyum Hidroksit (TMAH) çözeltileri kullanılmıştır. Islak aşındırma işlemi için SiO2 maske kullanılmıştır. Değişik geometrilerde daha keskin nano iğneler elde edebilmek için litografi maske geometrisi ve açıları optimize edilmiştir. Çalışma neticesinde yüksek en boy oranına sahip nano iğneler, kare piramit geometrili ve asimetrik beşgen piramit geometrili nano iğneler üretilebilmiştir.
Abstract Surgical masks are one of the most widely used personal protective equipment to keep pandemics under control. Medical face masks help slow the spread of the coronavirus (SARS-CoV-2) that causes COVID-19. Due to their lower cost and comfort, surgical masks are mostly preferred for the prevention of the epidemic. There are dozens of different face masks in the market. However, users do not have the opportunity to scientifically evaluate masks and analyze their performance against viruses. Surgical masks are classified according to EN 14683 standard but, the testing standards has been standardized considering bacterial permeability. In this study, a simple surgical mask testing approach has been demonstrated based on Quartz Crystal Microbalance (QCM) technique and variety of commonly available surgical masks’ aerosol filtration performances were compared using the proposed approach. Then, SEM images of some masks were taken, and the results obtained from SEM analysis were compared with the results that was taken by proposed mask testing approach. In short, a simple direct mask test method taking into account the entire human aerosol distribution is proposed. Copyright © 2022 American Association for Aerosol Research Graphical Abstract
A table-top microdevice was introduced in this work to produce ultrasmall particles for drug delivery via inhalation. The design and operation are similar to that of spray-drying equipment used in industry, but the device itself is much smaller and more portable in size, simpler to operate and more economical. More importantly, the device enables more accurate control over particle size. Using Flavopiridol, an anti-inflammation medication, formulations have been developed to produce inhalable particles for pulmonary delivery. A solution containing the desired components forms droplets by passing through an array of micro-apertures that vibrate via a piezo-electrical driver. High-purity nitrogen gas was introduced and flew through the designed path, which included the funnel collection and cyclone chamber, and finally was pumped away. The gas carried and dried the micronized liquid droplets along the pathway, leading to the precipitation of dry solid microparticles. The formation of the cyclone was essential to assure the sufficient travel path length of the liquid droplets to allow drying. Synthesis parameters were optimized to produce microparticles, whose morphology, size, physio-chemical properties, and release profiles met the criteria for inhalation. Bioactivity assays have revealed a high degree of anti-inflammation. The above-mentioned approach enabled the production of inhalable particles in research laboratories in general, using the simple table-top microdevice. The microparticles enable the inhalable delivery of anti-inflammation medicine to the lungs, thus providing treatment for diseases such as pulmonary fibrosis and COVID-19.
The interest in patterned polyvinylidene fluoride (PVDF) surfaces has grown significantly in the recent years due to ability to control the ferroelectric behavior through the size and shape of the surface structures. However, forming micron sized structures on the PVDF surface generally requires laborious lithography based methods or use of templates which complicates the process. In this study, we report spontaneous formation of microislands with ferroelectric response during PVDF growth via initiated chemical vapor deposition. Depositions performed under continuous and no flow conditions show that laminar precursor flow to the surface yield homogenous thin films, whereas no flow conditions of the batch mode result in the growth of surface protrusions (microislands) with higher polar phase content. Formation of these surface instabilities after an incubation time indicates the presence of local stress fields building with time, resulting in formation of the islands with higher β phase fraction to release the stress. Furthermore, the increased mobility of the polymer chains at high temperatures reduces the stress field, leading to lower β/α phase ratios in smaller microislands.
While molecular-level structural information is readily available for n-alkanethiol self-assembled monolayers (SAMs) on noble metal surfaces, the same cannot be claimed for dithiol-based SAMs due to their lack of long-range-order. This work provides molecular-level structural information on dithiol SAMs by investigating 5-( octyloxy)-1,3-phenylenedimethanethiol (OPDT) SAMs on Au(111) surfaces, using combined high-resolution scanning tunneling microscopy (STM), atomic force microscopy (AFM), and nanolithography. The high coverage OPDT SAMs do not exhibit long-range order. Desorption of these OPDT SAMs leads to the formation of ordered domains known as the striped phases, whose unit mesh is revealed as commensurate with the underlying Au(111) lattice. In these domains, OPDT molecules are lying-down, with the benzene ring and the zigzag plane of the alkyl chain parallel to the Au(111) surface. At the boundaries of these ordered structures, standing-up OPDT molecules are frequently present with an intermolecular space of 1 nm (i.e., 1D ordered structures). Using these ordered structures as internal standards in situ, the structure of the high-coverage OPDT SAMs is revealed: a mixture of standing-up and lying-down molecules randomly distributed on Au(111); as such, these SAMs exhibit little long-range order or ordered domains. The two thiols of each OPDT molecule occupy triple hollow sites on Au(111) surfaces. In the standing-up configuration, the benzene ring is perpendicular to the surface. In the lying-down con-figuration, the benzene ring and zigzag plane of the alkyl chain are parallel to the Au(111) surface. This work represents a high-resolution and molecular-level structural characterization of functionalized dithiol SAMs, furthering our understanding of dithiol molecule-surface interactions and the unique properties of these SAMs.
Coronavirus (SARS-CoV-2) is a respiratory infection virus that was first detected in Wuhan, China. The virus causes COVID-19 disease and the outbreak was recognised as a pandemic by the World Health Organization (WHO) in March 2020. SARS-CoV-2 virion was first imaged using cryo-electron microscopy by the Chinese Center for Disease Control and Prevention (CDC). Atomic Force Microscopy is a unique technique that can allow imaging of biomolecules under different conditions. In this work, we used Atomic Force Microscopy to characterize SARS-CoV-2 on tissue culture polystyrene (TCPS) and glass coverslip surfaces. We isolated SARS-CoV-2 and drop casted it on coverslip glass and tissue culture polystyrene surfaces. We analyzed height profiles, density, and aggregation behavior of the virion on glass and polystyrene surfaces. We observed the coffee ring effect on the drop casted samples and close packing of virions near the coffee rings on both surfaces with relatively higher virion distribution on the tissue culture polystyrene (TCPS) substrates. We compare virion agglomeration on the two types of surfaces. Finally, we applied ethanol disinfectant to virions on the surface to visualize the effect of ethanol and image the ultrastructure of SARS-CoV-2.
In this publication, we describe the design of a new fiber Fabry-Pérot interferometer and employ this to a low temperature atomic force/magnetic force microscope (LT-AFM/MFM) operating in the 4-300 K temperature range. A multilayer dielectric mirror coated optical fiber is used to achieve unprecedented 1 fm/Hz noise level, while the shot noise limit is 0.51 fm/Hz. The cavity length is adjustable, and the fiber can be brought within a very close proximity of the cantilever using a dedicated 2 mm stroke piezonanopositioner integrated on the piezotube scanner. The same nanopositioner also is used to park the fiber at a safe parking location during cantilever exchange. We demonstrate the performance of the LT-AFM/MFM by imaging the ITO thin film at 300 K, atomic steps on HOPG at 300 K, magnetic bits on the hard disk at 15 K, and the Abrikosov vortex lattice in the BSCCO(2122) single crystal at 4 K.
While self-assembly of molecules is relatively well-known and frequently utilized in chemical synthesis and materials science, controlled assembly of molecules represents a new concept and approach. The present work demonstrates the concept of controlled molecular assembly using a nonspherical biomolecule, heparosan tetrasaccharide (MW = 1.099 kD). The key to controlled assembly is the fact that ultrasmall solution droplets exhibit different evaporation dynamics from those of larger ones. Using an independently controlled microfluidic probe in an atomic force microscope, sub-femtoliter aqueous droplets containing designed molecules produce well-defined features with dimensions as small as tens of nanometers. The initial shape of the droplet and the concentration of solute within the droplet dictate the final assembly of molecules because of the ultrafast evaporation rate and dynamic spatial confinement of the droplets. The level of control demonstrated in this work brings us closer to programmable synthesis for chemistry and materials science which can be used to develop vehicles for drug delivery and three-dimensional nanoprinting in additive manufacturing.