Alveolar adenoma and coexisting atypical adenomatous hyperplasia: a case report and literature review.

Alveolar adenoma is a rare tumour of the lung. It is typically found in asymptomatic adults as a peripheral or subplerual nodule on imaging examination. Microscopically, the tumour is composed of admixture of epithelial and mesenchymal component in variable sized cystic or alveolar structures. The tumour shows a benign nature. There have been no reported recurrences or metastases. Malignant transformation of alveolar adenoma and coexisting with lung carcinoma have been rarely described. In this article, we report a case of an alveolar adenoma and coexisting atypical adenomatous hyperplasia. This case, contributing to the limited numbers of cases described to date, illustrates the importance of awareness on the possibility of alveolar adenoma being associated with lung carcinoma and its precursor lesions especially when diagnosed by small biopsy specimens.

High efficiency sperm enrichment from forensic mock samples in bubble-based acoustic filtration devices for short tandem repeat (STR) analysis.

A bubble-based acoustofluidic filtration (BAF) microfluidic device, which employs cross-flow filtration (CFF) and acoustic streaming, separates cells with high efficiency for forensic analysis. Forensic samples are typically complex and contain a substantial number of squamous epithelial cells from the female vagina, which tend to have fouling problems during filtration due to their morphological and cell adhesion differences. To overcome this issue, the BAF device utilizes bubble oscillation by bulk acoustic wave (BAW) to generate acoustic streaming, which offers additional hydrodynamic forces for side flushing cleaning and achieves effective removal within a mere 0.5 seconds. Our device is tested with imbalanced cell mixtures of sperm and epithelial cells with large disparity ratios. By concurrently employing CFF and acoustic streaming, the samples with our sperm-enrichment can achieve 91.72-97.78% for the recovery rate and 74.58-89.26% for the purity in the sperm enrichment. They are further subjected to short tandem repeat (STR) profiling, enabling the identification of perpetrators. Notably, even samples with minimal sperm cells demonstrated a significant increase in the male donor DNA ratio, while the peak heights of female alleles became virtually undetectable. The exceptional cell separation capability demonstrated by our BAF device highlights its potential applications in forensic sciences and other areas of cell biology.

Origami-Inspired Conductive Paper-Based Folded Pressure Sensor with Interconnection Scaling at the Crease for Novel Wearable Applications.

Drawing inspiration from origami structures, a pressure sensor was developed with unique interconnection scaling at its creases crafted on a conductive paper substrate, paving the way for advanced wearable technology. Two screen-printed conductive paper substrates were combined face-to-face, and specific folds were introduced to optimize the sensor structure. The Electrical Contact Resistance (ECR) was systematically analyzed across different fold numbers and crease gaps, revealing a notable trade-off: while increasing the number of folds expanded the sensing area, it also influenced the ECR, reaching a performance plateau. Strategic modifications in the sensor's design, including refining interconnections at the crease, enhanced its sensitivity and stability, culminating in a remarkable sensitivity of 3.75 kPa-1 at subtle pressure levels (0-0.05 kPa). This sensor's real-world applications proved to be transformative, from detecting bruxism and aiding in neck posture correction to remotely sensing trigger finger locking phenomena, highlighting its potential as a pivotal tool in upcoming medical diagnostics and treatments.

Pipette-operable microfluidic devices with hydrophobic valves in sequential dispensing with various liquid samples: multiplex disease assay by RT-LAMP.

Microfluidic dispensing technologies often require additional equipment, posing challenges for their integration into point-of-care testing (POCT) applications. In response to this challenge, we have developed a pipette-operable microfluidic device fabricated using 3D printing technology for precise liquid dispensing. This device features three reaction chambers and three distinct hydrophobic valves to control the flow direction of liquids. Through these valves, the pipette-operable microfluidic device can sequentially dispense and isolate the liquid into the three reaction chambers, allowing for the individual conduction of three distinct reactions. These hydrophobic valves, with optimized flow resistance and burst pressure, can sustain a volumetric flow rate of up to 25 µL s-1, making them compatible with a standard pipette, a syringe, or a dropper operation. Furthermore, the device is successfully used to operate with various liquids, including BSA, DMEM, FBS, plasma, and blood, representing that the device has the potential to be used for various applications. Additionally, distinct RT-LAMP primer sets have been incorporated for diagnosing SARS-CoV-2, influenza A, and influenza B within each chamber through lyophilization. This pipette-operable microfluidic device serves as a versatile tool for diagnosing these three diseases using a single loading process, with results readable by the naked eye or image assay within 30 minutes of incubation. Finally, the design concepts are extended to engineer a microfluidic device with 20 reaction chambers, offering significant potential for multi-disease diagnostics.

Using single-molecule approaches to study archaeal DNA-binding protein Alba1.

Thermophilic and hyperthermophilic archaea have one or more copies of the Alba gene, which encodes Alba, a dimeric, highly basic protein that binds cooperatively to DNA. However, the functions of Alba and how it interacts with DNA remain unclear. In this study, we have used single-molecule tethered particle motion (TPM) and optical tweezers (OT) experiments to study the interactions between DNA molecules and Alba1. When Alba1 binds to double-stranded DNA, the Brownian motion (BM) amplitude for DNA tethers increases continuously, suggesting that Alba1 binds cooperatively. The OT study confirmed that a 5-fold increase in the persistence length of the Alba1 nucleoprotein filament is the major factor causing the increase in the BM amplitude for DNA tethers, while the contour length remained mostly unchanged. Moreover, the rate of the increase in the BM amplitude and the BM plateau value are both DNA length-dependent, indicating that the number of Alba1 initiation binding sites increases as the DNA becomes longer. Using the incoming-strand TPM experiment to monitor the interaction between Alba1 nucleoprotein filaments, we found that significant dimer-dimer contacts between two Alba1 nucleoprotein filaments are present, and the interaction is regulated by the concentration of Alba1.

Contact angle hysteresis on textured surfaces with nanowire clusters.

Nanowire arrays with various agglomeration patterns were synthesized by adjusting the solvent evaporation rates. Nanowires with 200 nm diameter and 2-25 microm in length were fabricated from an anodic aluminum oxide (AAO) porous template. Various drying treatments were applied to develop nanostructured surfaces with topological differences. Due to surface tension forces, copper nanowires after thermal and evaporative drying treatments agglomerated into clusters, while supercritical drying technique provided excellent bundled-free and vertically-standing nanowire arrays. Although all dried surfaces exhibited hydrophobic nature, the contact angle hysteresis, or the difference between advancing and receding angles, was found to be larger on those surfaces with bundled nanowire clusters. To explain the difference, the wetted solid fraction on each surface was calculated using the Cassie-Baxter model to show that the hysteresis was contributed by liquid/solid contact area on the textured surfaces.

Skin-Inspired Tactile Sensor on Cellulose Fiber Substrates with Interfacial Microstructure for Health Monitoring and Guitar Posture Feedback.

Skin-inspired flexible tactile sensors, with interfacial microstructure, are developed on cellulose fiber substrates for subtle pressure applications. Our device is made of two cellulose fiber substrates with conductive microscale structures, which emulate the randomly distributed spinosum in between the dermis and epidermis layers of the human skin. The microstructures not only permit a higher stress concentration at the tips but also generate electrical contact points and change contact resistance between the top and bottom substrates when the pressure is applied. Meanwhile, cellulose fibers possessing viscoelastic and biocompatible properties are utilized as substrates to mimic the dermis and epidermis layers of the skin. The electrical contact resistances (ECR) are then measured to quantify the tactile information. The microstructures and the substrate properties are studied to enhance the sensors' sensitivity. A very high sensitivity (14.4 kPa-1) and fast recovery time (approx. 2.5 ms) are achieved in the subtle pressure range (approx. 0-0.05 kPa). The device can detect subtle pressures from the human body due to breathing patterns and voice activity showing its potential for healthcare. Further, the guitar strumming and chord progression of the players with different skill levels are assessed to monitor the muscle strain during guitar playing, showing its potential for posture feedback in playing guitar or another musical instrument.

Digital Microfluidic qPCR Cartridge for SARS-CoV-2 Detection.

Point-of-care (POC) tests capable of individual health monitoring, transmission reduction, and contact tracing are especially important in a pandemic such as the coronavirus disease 2019 (COVID-19). We develop a disposable POC cartridge that can be mass produced to detect the SARS-CoV-2 N gene through real-time quantitative polymerase chain reaction (qPCR) based on digital microfluidics (DMF). Several critical parameters are studied and improved, including droplet volume consistency, temperature uniformity, and fluorescence intensity linearity on the designed DMF cartridge. The qPCR results showed high accuracy and efficiency for two primer-probe sets of N1 and N2 target regions of the SARS-CoV-2 N gene on the DMF cartridge. Having multiple droplet tracks for qPCR, the presented DMF cartridge can perform multiple tests and controls at once.

Droplet Transportation through an Orifice on Electrode for Digital Microfluidics Modulations.

A digital microfluidic modular interface (chip-to-chip interface) which possesses an electrode with an orifice to vertically transport core-shell droplets is presented. The electrodes were geometrically designed to promote droplet deformation and suspension. The droplets were then applied with an electrical potential for insertion into and passage through the orifice. The concepts were tested with three types of droplets at the volume of 0.75~1.5 µL, which is usually difficult to transfer through an orifice. The integration of electrowetting on dielectric (EWOD) with paper-based microfluidics was demonstrated: the droplet could be transported within 10 s. More importantly, most of the core droplet (~97%) was extracted and passed through with only minimal shell droplets accompanying it.

High-Throughput White Blood Cell (Leukocyte) Enrichment from Whole Blood Using Hydrodynamic and Inertial Forces.

A microfluidic chip, which can separate and enrich leukocytes from whole blood, is proposed. The chip has 10 switchback curve channels, which are connected by straight channels. The straight channels are designed to permit the inertial migration effect and to concentrate the blood cells, while the curve channels allow the Dean flow to further classify the blood cells based on the cell sizes. Hydrodynamic suction is also utilized to remove smaller blood cells (e.g., red blood cell (RBC)) in the curve channels for higher separation purity. By employing the inertial migration, Dean flow force, and hydrodynamic suction in a continuous flow system, our chip successfully separates large white blood cells (WBCs) from the whole blood with the processing rates as high as 1 × 108 cells/sec at a high recovery rate at 93.2% and very few RBCs (~0.1%).

Ciliated Muconodular Papillary Tumors of the Lung.

Ciliated muconodular papillary tumor is a rare tumor of the lung with 38 cases reported to date in the English literature. It is typically found incidentally in older adults (average age, 67 years) as a small, peripheral, ground glass opacity or nodule on computed tomography. Microscopically, the tumor is composed of a mixture of ciliated columnar, mucous, and basal cells in a variety of architectural patterns including glandular, papillary, lepidic, and micropapillary growth patterns. Recently, studies have shown the tumor has several associated gene alterations, supporting that the lesion is indeed neoplastic. The tumor seemingly follows an indolent clinical course, as there have been no reported recurrences or metastases. In this article, we review the clinical, radiographic, pathologic, and molecular findings of ciliated muconodular papillary tumors. Diagnostic pitfalls and the diagnostic considerations are discussed.

Microfluidic Time-Delay Valve Mechanism on Paper-Based Devices for Automated Competitive ELISA.

Paper-based technologies have been drawing increasing attentions in the biosensor field due to their economical, ecofriendly, and easy-to-fabricate features. In this paper, we present a time-delay valve mechanism to automate a series of procedures for conducting competitive enzyme-linked immunosorbent assay (ELISA) on a paper-based device. The mechanism employs a controllable time-delay valve, which has surfactants to dissolve the hydrophobic barriers, in a fluid pathway. The valves can regulate the liquid and sequentially deliver the sample flow for automating ELISA procedures in microchannels. Competitive ELISA is achieved in a single step once the sample, or small molecule pesticide (e.g., Imidacloprid), is applied onto the paper-based device with a comparable sensitivity to plate-based competitive ELISA. The results further demonstrate the appositeness of using paper-based devices with the valve designs for on-the-go ELISA detection in agriculture and biomedical applications.

Enhancement of microfluidic particle separation using cross-flow filters with hydrodynamic focusing.

A microfluidic chip is proposed to separate microparticles using cross-flow filtration enhanced with hydrodynamic focusing. By exploiting a buffer flow from the side, the microparticles in the sample flow are pushed on one side of the microchannels, lining up to pass through the filters. Meanwhile a larger pressure gradient in the filters is obtained to enhance separation efficiency. Compared with the traditional cross-flow filtration, our proposed mechanism has the buffer flow to create a moving virtual boundary for the sample flow to actively push all the particles to reach the filters for separation. It further allows higher flow rates. The device only requires soft lithograph fabrication to create microchannels and a novel pressurized bonding technique to make high-aspect-ratio filtration structures. A mixture of polystyrene microparticles with 2.7 µm and 10.6 µm diameters are successfully separated. 96.2 ± 2.8% of the large particle are recovered with a purity of 97.9 ± 0.5%, while 97.5 ± 0.4% of the small particle are depleted with a purity of 99.2 ± 0.4% at a sample throughput of 10 µl/min. The experiment is also conducted to show the feasibility of this mechanism to separate biological cells with the sample solutions of spiked PC3 cells in whole blood. By virtue of its high separation efficiency, our device offers a label-free separation technique and potential integration with other components, thereby serving as a promising tool for continuous cell filtration and analysis applications.

Efficient SNP Discovery by Combining Microarray and Lab-on-a-Chip Data for Animal Breeding and Selection.

The genetic markers associated with economic traits have been widely explored for animal breeding. Among these markers, single-nucleotide polymorphism (SNPs) are gradually becoming a prevalent and effective evaluation tool. Since SNPs only focus on the genetic sequences of interest, it thereby reduces the evaluation time and cost. Compared to traditional approaches, SNP genotyping techniques incorporate informative genetic background, improve the breeding prediction accuracy and acquiesce breeding quality on the farm. This article therefore reviews the typical procedures of animal breeding using SNPs and the current status of related techniques. The associated SNP information and genotyping techniques, including microarray and Lab-on-a-Chip based platforms, along with their potential are highlighted. Examples in pig and poultry with different SNP loci linked to high economic trait values are given. The recommendations for utilizing SNP genotyping in nimal breeding are summarized.

Melting analysis on microbeads in rapid temperature-gradient inside microchannels for single nucleotide polymorphisms detection.

A continuous-flow microchip with a temperature gradient in microchannels was utilized to demonstrate spatial melting analysis on microbeads for clinical Single Nucleotide Polymorphisms (SNPs) genotyping on animal genomic DNA. The chip had embedded heaters and thermometers, which created a rapid and yet stable temperature gradient between 60 °C and 85 °C in a short distance as the detection region. The microbeads, which served as mobile supports carrying the target DNA and fluorescent dye, were transported across the temperature gradient. As the surrounding temperature increased, the fluorescence signals of the microbeads decayed with this relationship being acquired as the melting curve. Fast DNA denaturation, as a result of the improved heat transfer and thermal stability due to scaling, was also confirmed. Further, each individual microbead could potentially bear different sequences and pass through the detection region, one by one, for a series of melting analysis, with multiplex, high-throughput capability being possible. A prototype was tested with target DNA samples in different genotypes (i.e., wild and mutant types) with a SNP location from Landrace sows. The melting temperatures were obtained and compared to the ones using a traditional tube-based approach. The results showed similar levels of SNP discrimination, validating our proposed technique for scanning homozygotes and heterozygotes to distinguish single base changes for disease research, drug development, medical diagnostics, agriculture, and animal production.