1,721,152 research outputs found
Development of integrated whole-teflon microfluidic film chips
No full textMicrofluidic technology has emerged as a powerful tool in various scientific and industrial fields, such as micro-and nanofabrication, chemical synthesis, single-cell analysis, pharmaceutics, wearable electronics, and point-of-care diagnostics. The rapid growth in these disciplines is driven by the increasing synergy between device materials and microfluidic capabilities. Traditional materials in microfluidics often present limitations that impede the performance and application scope of microdevices. Recently, perfluorinated polymers (Teflon) have gained attention as an alternative material for microfluidics due to their exceptional chemical resistance and surface inertness. Despite their potential, challenges remain in developing efficient fabrication methods for integrated Teflon microfluidic devices for practical applications, such as flow chemistry. This thesis presents a series of studies on microfluidic technology, focusing on innovative microfabrication methods using Teflon materials and the applications of Teflon devices. Key issues addressed include the development of microfabrication strategies for thin Teflon films, the integration of microfluidic components, and the application of Teflon microfluidic devices in flow chemistry. Specifically, this thesis introduces fabrication methods, distinct from conventional approaches, for the production of microfluidic chips with thin Teflon films. Additionally, this thesis explores the development and integration of robust, high-performance microfluidic components—such as interconnectors, micromixers, microvalves, and microelectrodes—into the developed microfluidic platforms. The integrated Teflon microfluidic film chips demonstrate their utility in flow chemistry applications, such as photochemical synthesis. The first section introduces Teflon-based microfluidic devices fabricated using a cost-effective approach. These Teflon microfluidic film chips leverage the advantages of Teflon materials and thin film structures, offering exceptional chemical resistance, high transparency, flexibility, and efficient heat transfer. A robust chip-to-world interface is established through the development of adhesive-free, solvent-resistant interconnectors; and the easy integration and functionalization of microvalves for fluid manipulation was demonstrated. As a proof of concept, the versatility and enhanced performance of Teflon microfluidic film chips in flow chemistry are validated through an on-chip photochemical reaction. The second section presents a simplified and scalable fabrication method for whole-Teflon microfluidic film devices. This method provides a scalable, cost-effective solution for producing film-based Teflon microfluidic devices with enhanced production efficiency and commercialization potential. The resulting devices are significantly thinner and more flexible, capable of covering large areas with extended microchannels. Various chip configurations, including 3D microfluidic networks and multiple inlets, are achievable. Microelectrodes are easily integrated into the Teflon film chips for electrochemical applications. The favorable properties of these film chips for flow chemistry applications, such as efficient heat transfer, waterproofing, and air impermeability, are demonstrated. The third section reports a 3D micromixer based on the splitting–stretching–recombination (SSR) of streams to facilitate molecular diffusion, effectively mixing solutions with low Reynolds numbers (0.01–10). The micromixer fabrication involves two-photon polymerization (2PP) 3D printing and soft lithography, offering high resolution and reproducibility. The micromixer features a highly compact design and can be easily integrated into microfluidic platforms. It achieves high mixing efficiency for low-Re solutions (flow rates ≤60 μL/min) with a mixing volume smaller than 20 nL, and the complete mixing time is in the range of milliseconds. The device maintains high performance with highly viscous solutions and solutions containing macromolecules and nano-sized colloids.</p
Point-of-care pathogen detection based on isothermal amplification methods
No full textThe identification of pathogenic organism is essential to the prevention and distinguish the problems connected with health and safety. The growing public concern over the spread of the disease and the tough legislation in food industry made the failure to detect an infection might cause dreadful consequences. People are looking forward to obtaining the analytical results as soon as possible, the traditional pathogen detection protocol spend up to 6 to 10 days to yield an answer. Such long period is dissatisfactory, and many experts have geared their efforts towards the rapid, sensitivity methods. The availability of modern detection platforms plays a key role in the speed and accuracy of monitoring, surveillance, and quantitative infectious biological agent, and has a major influence on enacts regulations to promote the best practices to prevent pathophoresis. In the past four years, my studies were basically focused on developing convenient and effective isothermal amplification based methods for rapid pathogen detection and combining different techniques for nucleic acid quantitative analysis. On the basis of developed isothermal amplification detection technique, I explored its applications in POCT device, which exhibited great potentials in the electricity-free and equipment–free pathogen detection in field. Also, microfluidic technology minimized the POCT device with the help of novel valve design. In the first chapter, an overview of POCT device for nucleic acid analysis devices including their significance, current advances and challenges are present. In the rest chapters, I present the research projects completed during my PhD study, including development of real-time recombinase polymerase amplification (RPA) assay for rapid detection of Herpes simplex virus-1 (HSV-1) in human tears, POCT in the field: a hand-powered and sample-in-answer-out device (HASDE) for nucleic acid detection without the requirement of electrical supply and extra equipment and a new paradigm for valve design in microfluidic chip for the facile isothermal sample-in-answer-out nucleic acid identification.</p
A highly efficient microfluidic particles removal device with staggered herringbone micromixers
No full textParticulate matter (PM) has caused a significant challenge to our daily life. The effect included severe air pollution, the health threat, and climate change by absorbing and scattering solar radiation. Due to the mechanism of the traditional filter, they cannot achieve the high removal efficiency and the low air pressure drop simultaneously, which dramatically limits our daily life and industrial production. In pollution analysis, the current method requested to select the specific filter for the target analyte and then collect the sample over several weeks. Therefore, we only analyze partial components without real-time information. My MPhil studies mainly focused on exploring portable, easy transportation and storage, combined with the high removal efficiency and the low-pressure drop microfluidic device for the PM particle collection and composition analysis. Based on a typical mixer of the microfluidic device, I adopted it as the main component in the PM collector to capture the PM particles. Also, the performance of the chip is further optimized by the surface modification and the nanoparticle filler. I give a general overview of the microfluidic chips, including their significance, materials, fabrication techniques, components, and their application in environmental analysis. In the rest chapters, I presented the research projects completed during my MPhil study, including the device's design, simulating the expected result by COMSOL, measured its practical performance by liquid and solid particles. Then I also proved its potential in the whole function on-site sample collection and composition analysis by increasing its thermal stability.</p
A rapid self-healing host-guest supramolecular hydrogel : high mechanical strength and excellent biocompatibility for potential biomedical applications
No full textHydrogels are commonly used in tissue engineering due to their excellent biocompatibility, hydrophilicity, and tissue-like structure. They have shown good support as a primary material in the field of cartilage repair. However, further research and development have revealed some drawbacks and shortcomings of reported hydrogels in terms of mechanical strength and biocompatibility. It was seen that the mechanical behavior of hydrogels was not comparable to that of native tissues. To address the issue, a three-armed host-guest supramolecule (HGSM) was created through covalent cross-linking. This HGSM was then utilized to develop a novel hydrogel that incorporates supramolecular interactions along with covalent interactions into a cross-linked network. It results in a unique structure that enhances the mechanical properties of the hydrogel. The three-armed HGSM was prepared through effective supramolecular host-guest inclusion interactions between isocyanatoethyl acrylate-modified β-cyclodextrin (β-CD-AOI2) and acryloylated tetra-ethylene glycol-modified adamantane (A-TEG-Ad). The photo-crosslinking reaction was carried out under the photoactive compound ""irgacure"" to form a host-guest (HG) complex, subsequently, the supramolecular hydrogel was formed. The HGSM arms were further complexed with polyvinyl alcohol/chitosan (PVA/CS; PC) to form an interwoven polymeric network (HGSM-PC). It is worth noting that PC-impregnated hydrogels exhibit a wide temperature response range, flexibility, and sensitivity, making them suitable as tissue weight-bearing scaffolds. We found that the HGSM-PC had excellent robustness, fatigue resistance, self-healing properties, and reproducibility due to the covalent cross-linking that maintains its overall shape. This paper outlines the structural features and preparation methods of novel hydrogels that effectively heal and dissipate energy, preventing destructive fracture extension. The hydrogels exhibit higher strength and desired biocompatibility.</p
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
3D printing-replication microfabrication techniques and an integrated, individually-addressable microfluidic single-cell array chip
No full textThree-dimensional (3D) printing is an intriguing and facile material processing method that enables quick turnaround of complicated structures from concept to prototype. Different mechanism-based 3D printers have high demands for suitable material categories. In another aspect, microfluidic platforms offer the most important contributions to biological and chemical analysis due to the low sample consumption, small size, and high integration. The miniaturized size of microfluidic devices is particularly convenient in single-cell studies, which unveils cell heterogeneity related to a top human killer, cancer. Microfluidics benefit greatly from 3D printing for the rapid fabrication of molds, but the limitation of printable material categories impedes the creation of 3D microfluidic structures in desired materials. It would also be interesting to incorporate 3D structures in a single-cell study platform. There are three projects in my work, which are divided into two parts. One is to explore novel methods to fabricate complicated 3D structures in desired materials. Another is to build up an integrated and individually-addressable microfluidic single-cell array. In the first part, we demonstrated replicating 3D printed structures into functional materials by constructing a non-porous, heat-resistance nickel mold. Complicated structures with overhanging structures were reconstructed in polydimethylsiloxane (PDMS), paraffin, and polyacrylamide replicas. The method displays high fidelity and high resolution (< 1 μm). Moreover, we reduced the feature size of the 3D replica by electroless plating the interior of the nickel mold. The cost-effective electroless plating was further employed to deposit thick metal films in both PDMS microchannels and patterned PDMS sheets. The as-plated hollow nickel mold can be sacrificed to create Teflon chips; the freestanding microcomponents, such as microgears, can also be used in microelectromechanical systems (MEMS). We believe our 3D-replication methods can inspire other researchers to fabricate 3D structures in desired materials, whether unextrudable Teflon or rigid nickel, without direct 3D printing. In the second part, we constructed a microfluidic single-cell array chip that can realize addressable cell release at low cost. With rational geometric designs, we realized high cell capture efficiency (~90%) and release of a single cell in a 10 x 10 array. Asymmetric microelectrode pairs were devised to produce addressable electrolytic bubbles in the 10 x 10 microelectrode array (MEA). This platform combines passive and active manipulation techniques to control the motion of a single cell. We believe this device is promising to be coupled with a downstream single-cell module and form a cost-economical single-cell analysis platform.</p
Fabricating balloon-like PDMS membranes for trapping C. elegans
No full textCaenorhabditis elegans is widely used as a model organism in biological research. A microfluidic chip with a gas channel layer and a PDMS membrane layer with hemispherical balloon arrays was proposed to address the trade-offs between reversible trapping and precise manipulation of C. elegans. The PDMS membranes with balloon structures were speculated to store more elastic potential energy, allowing for greater elastic deformation before rupture. When the air pressure was increased, the membrane was caused to inflate, trapping the worms in the depressions between the inflated sections. Compression molding was utilized to fabricate the PDMS balloon array, and the factors controlling membrane thickness, the thermal deformation phenomenon in compression molds, and the curing conditions of PDMS prepolymer were evaluated. Different PDMS-PDMS bonding methods were also assessed. Testing showed that the pneumatically actuated PDMS balloons could enable controlled balloon expansion but could not impede the movement of individual nematodes. This versatile platform is believed to provide a promising immobilization approach for C. elegans and potentially other model organisms. Further research is needed to improve the method, including the design of the gas channel and other combinations of upper and lower molds.</p
Optimization of HiPSCs differentiating into PPs and mechanism study of gene expression noise
No full textHuman induced pluripotent stem cells (hiPSCs) hold significant potential for cell replacement therapy due to their capacity to differentiate into various cell types. Pancreatic progenitors (PPs) are key intermediate cells in the differentiation of hiPSCs into pancreas cells. However, obtaining uniformly mature PPs remains challenging. Moreover, gene expression is also influenced by gene noise, which can result in stochastic gene expression and subsequent cell heterogeneity. Therefore, it is both essential to develop a universal platform for optimizing hiPSCs differentiation into PPs and to uncover the generation mechanisms of gene noise. In the first part, we established an hiPS cell line with four-reporter genes to monitor marker gene expression and developed a microwell array to mimic the in vivo environment. Based on these two achievements, we could track and analyze cells in real-time or in situ during differentiation. Finally, we successfully optimized the factor combination for hiPSCs differentiation into PPs in 3D environment and efficiently obtained homogeneous Pdx1+ pancreatic organoids. We believe this research can contribute to the development of cell replacement therapy for diabetes. In the second part, we established light-inducible cell lines and developed illumination devices. We observed large noise generated by amplitude modulation (AM) light with intermediate intensity, while this noise could be regulated by pulse-width modulation (PWM) light. We proposed that the noise was induced by the interaction of p65AD and CBP/p300. To validate this hypothesis, we conducted various experiments, including disrupting CBP/P300 HAT activities, assessing histone acetylation and chromatin accessibility through next-generation sequencing (NGS), and evaluating transcriptional noise via mRNA counts, and so on. All these experiments supported our hypothesis. Furthermore, we found that this hypothesis might be also universal in endogenous genes expression in mammalian cells. This research can offer a mechanism-based approach to modulate gene expression noise and is beneficial for studying cell-fate control.</p
Fabrication and applications of microfluidic systems on tumor organoids
No full textOrganoids serve as valuable biomedical models for investigating human diseases and conducting drug screening, despite limitations in cell type diversity, spatial organization, and microenvironment. They often display significant heterogeneity in morphology, cell distribution, and quantity due to the absence of precise physical and chemical control over the microenvironment, as well as the intricacy and imprecision of manual procedures. The integration of microfluidic technology can effectively address these challenges by facilitating the development of tumor organoids that mimic essential structural and functional aspects of target organs in vivo. Engineered systems approaches can be utilized to fabricate, regulate, and quantify organoids and their microenvironments, leveraging high-throughput automated manufacturing, operation, and monitoring of organoids with dynamic intelligent control to minimize heterogeneity and tailor the process for precision medicine. To achieve this objective, we propose a microfluidic chip capable of generating logarithmic step-wise concentrations in each layer, providing two types of drugs and 16 distinct drug concentration combinations for culture conditions. The biochemical composition of the microenvironment can be manipulated by imposing precise geometric constraints to establish and sustain concentration gradients. The identification and segregation of organoids based on their morphological characteristics are essential for organoid culture and analysis. We introduce a microfluidic device integrated with microvalves for fluid control to sort organoids using image processing algorithms and size-based confirmation. The suggested morphology-activated organoid sorting system offers numerous advantages, including label-free operation, high sample resolution, gentle handling of organoids, and the ability to trap organoids within the device. Furthermore, the system is compact, automated, highly sensitive, portable, easily integrable with other technologies, and provides real-time detection.</p
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