Towards a Theory of Droplet-Mixing Graphs in Microfluidics

In this work, we study the problem of fluid mixing in microfluidic chips. The motivation for studying this problem comes from the process of sample preparation for chemical, biological, medical and environmental experiments, which often require preparation of fluid mixtures with desired concentrations. We assume that fluids are manipulated in discrete units called droplets. The input set of droplets consist of two distinct fluids: the reactant, which is the fluid of interest, and the buffer fluid that is used to dilute it. The goal is to produce a target set of droplets with prespecified reactant concentrations. In the model we study, the mixing process in a microfluidic chip can be abstractly represented as a mixing graph. A mixing graph is a collection of micro-mixers (nodes) connected by micro-channels (edges) that converts an input set of droplets I into a set of output droplets T, by applying a sequence of 1:1 mixing operations. This graph may also produce some waste, which are superfluous droplets of fluid not used in the target set. Computational complexity of most natural questions regarding such mixing graphs remain open. For example, it is not even known whether it is decidable for a given target set to be produced without waste. Current work in the literature contains only heuristic approaches that compute mixing graphs while attempting to optimize certain objectives, including minimizing waste, reactant usage, the depth of the graphs, and more.Our first contribution is an efficient algorithm for computing mixing graphs for single-droplet targets. Our algorithm produces significantly less waste than state-of-the-art algorithms in an experimental comparison. We also provide a bound on its worst-case performance that is significantly better than those for earlier algorithms. Our second result concerns the variant of the problem where the objective is to design a mixing graph that perfectly mixes a collection of input droplets with arbitrary concentrations. We provide a complete characterization of input sets for which such graphs exist, and an efficient algorithm to construct these graphs. In addition, we provide several other results about properties of mixing graphs and the computational complexity of computing mixing graphs of fixed depth

A NEW CONDUCTIVE MEMBRANE-BASED MICROFLUIDIC PLATFORM FOR ELECTROKINETIC APPLICATIONS

Micro-total-analysis-system (uTAS), a technology branches from the broader concept, microfluidics, has emerged as a powerful tool for many biological and chemical applications. uTAS typically features sample-to-answer designs, minute sample assumption and short processing time, which are highly desired in point-of-care diagnostics or high-throughput chemical analysis. Despite a large number of microfluidic devices reported with the uTAS concept, most designs were detection and sensitivity focused, ignored the necessary sample preparation steps. In recent years, the increasing demand for chip automation has boosted research efforts on sample preparation. Electric force serves as one of the most applicable tools among on-chip sample processing techniques due to its portable and easy-integrating nature. To date, research has yielded a large number of designs utilizing electric field as a driving force, also known as electrokinetics, for on-chip sample processing, such as sample purification, enrichment, mixing and sorting. One biggest issue researchers countered using electric field is undesired surface reactions that may cause Faradaic reactions, electrode corrosion, and contaminations. While several microfluidic platforms have been developed to address this issue, there are still growing efforts to create new micro-design that are capable of providing sufficient electric field with improved stability, portability, and robustness. This thesis seeks to address the electrokinetic-based on-chip sample preparation issue in two aspects, continuity and flow control, which represent two main challenges of on-chip sample preparation: a limited capability to continuously process samples and lacking necessary modules for precise flow control under large extent chip integration. We first developed a new electrokinetic platform with integrated conductive membranes to effectively generate a uniform three-dimensional electric field inside microfluidic channels. The new design also has proved superiorities in avoiding surface reactions, improving portability, and reducing the fabrication cost. We then solved the continuity issue with a free flow electrophoresis device created from the platform. The free flow nature of the device allows for continuous sample throughput while adding electric field perpendicularly offers additional manipulating factors. Utilizing the newly developed free flow electrokinetic chip, we have successfully demonstrated two common on-chip sample processing functions: parallel separation and sample enrichment. On the other hand, the flow control issue is tackled by creating essential on-chip control modules under microfluidic setting. We have designed several microfluidic units with the platform to facilitate on-chip flow regulation, including micro-pumps, a sample injector, a local flow meter and a potential automatic control panel. All the flow control modules can be directly integrated into any soft lithography based sample processing modules without affecting the original designs, which significantly eases the integration difficulty. The ultimate goal of this research shall lead to a microfluidic platform that can perform essential on-chip sample pretreatments in a continuous manner and allows need-based customization. The platform shall be easily integrated with essential power functions and feedback mechanisms for automatic flow control, which offer a possibility to real highly integrated portable devices. Eventually, we can build the real uTAS by combining the platform with our real-time biosensor and turning it into a sample-to-answer uTAS. In the first chapter of this thesis, a general background correlated to my research work is provided. The introduction includes the uTAS concept and its related technologies, explains the increasing demand for on-chip sample preparation techniques, and discusses current sample process modules using electrokinetic force. It leads to Chapter 2, where I summarize the current electrokinetic-based microfluidic platforms developed to address the surface reaction issue. Then we propose the new platform along with a theoretical model to characterize this design. An extensive comparison between available designs follows to demonstrate the advantages of this new platform, including the comparison specifically focusing on surface reactions. A detailed fabrication process flow is demonstrated in the end, showing how to fabricate this new platform design using one -step photolithography. Then the thesis splits into two parallel blocks, corresponding to the two challenges of on-chip sample preparation. The continuity challenge is addressed on the first block, chapter 3, where free flow electrophoresis device is presented and followed by two demonstrations of on-chip sample pretreatment functions: mixture separation and molecule enrichment. The second block of this thesis discusses the importance of on-chip flow control and the main obstacles that current technologies struggle with. Essential modules for on-chip flow control, such as electro-osmotic pumps, fluid regulation, sample injection techniques, pressure and flow meters, will be demonstrated in chapter 4-6, respectively. In conclusion, I will summarize all my previous research work and how to sketch the big picture of on-chip sample preparation with this platform. The results shall provide guidelines and inspirations for future on-chip sample preparation research

Microdevices and Microsystems for Cell Manipulation

Microfabricated devices and systems capable of micromanipulation are well-suited for the manipulation of cells. These technologies are capable of a variety of functions, including cell trapping, cell sorting, cell culturing, and cell surgery, often at single-cell or sub-cellular resolution. These functionalities are achieved through a variety of mechanisms, including mechanical, electrical, magnetic, optical, and thermal forces. The operations that these microdevices and microsystems enable are relevant to many areas of biomedical research, including tissue engineering, cellular therapeutics, drug discovery, and diagnostics. This Special Issue will highlight recent advances in the field of cellular manipulation. Technologies capable of parallel single-cell manipulation are of special interest

Lab-on-a-Chip Fabrication and Application

The necessity of on-site, fast, sensitive, and cheap complex laboratory analysis, associated with the advances in the microfabrication technologies and the microfluidics, made it possible for the creation of the innovative device lab-on-a-chip (LOC), by which we would be able to scale a single or multiple laboratory processes down to a chip format. The present book is dedicated to the LOC devices from two points of view: LOC fabrication and LOC application

Micro/nanofluidic and lab-on-a-chip devices for biomedical applications

Micro/Nanofluidic and lab-on-a-chip devices have been increasingly used in biomedical research [1]. Because of their adaptability, feasibility, and cost-efficiency, these devices can revolutionize the future of preclinical technologies. Furthermore, they allow insights into the performance and toxic effects of responsive drug delivery nanocarriers to be obtained, which consequently allow the shortcomings of two/three-dimensional static cultures and animal testing to be overcome and help to reduce drug development costs and time [2–4]. With the constant advancements in biomedical technology, the development of enhanced microfluidic devices has accelerated, and numerous models have been reported. Given the multidisciplinary of this Special Issue (SI), papers on different subjects were published making a total of 14 contributions, 10 original research papers, and 4 review papers. The review paper of Ko et al. [1] provides a comprehensive overview of the significant advancements in engineered organ-on-a-chip research in a general way while in the review presented by Kanabekova and colleagues [2], a thorough analysis of microphysiological platforms used for modeling liver diseases can be found. To get a summary of the numerical models of microfluidic organ-on-a-chip devices developed in recent years, the review presented by Carvalho et al. [5] can be read. On the other hand, Maia et al. [6] report a systematic review of the diagnosis methods developed for COVID-19, providing an overview of the advancements made since the start of the pandemic. In the following, a brief summary of the research papers published in this SI will be presented, with organs-on-a-chip, microfluidic devices for detection, and device optimization having been identified as the main topics.info:eu-repo/semantics/publishedVersio

Beyond solid-state lighting: Miniaturization, hybrid integration, and applications og GaN nano- and micro-LEDs

Gallium Nitride (GaN) light-emitting-diode (LED) technology has been the revolution in modern lighting. In the last decade, a huge global market of efficient, long-lasting and ubiquitous white light sources has developed around the inception of the Nobel-price-winning blue GaN LEDs. Today GaN optoelectronics is developing beyond lighting, leading to new and innovative devices, e.g. for micro-displays, being the core technology for future augmented reality and visualization, as well as point light sources for optical excitation in communications, imaging, and sensing. This explosion of applications is driven by two main directions: the ability to produce very small GaN LEDs (microLEDs and nanoLEDs) with high efficiency and across large areas, in combination with the possibility to merge optoelectronic-grade GaN microLEDs with silicon microelectronics in a fully hybrid approach. GaN LED technology today is even spreading into the realm of display technology, which has been occupied by organic LED (OLED) and liquid crystal display (LCD) for decades. In this review, the technological transition towards GaN micro- and nanodevices beyond lighting is discussed including an up-to-date overview on the state of the art

Non-covalent interactions in organotin(IV) derivatives of 5,7-ditertbutyl- and 5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine as recognition motifs in crystalline self- assembly and their in vitro antistaphylococcal activity

Non-covalent interactions are known to play a key role in biological compounds due to their stabilization of the tertiary and quaternary structure of proteins [1]. Ligands similar to purine rings, such as triazolo pyrimidine ones, are very versatile in their interactions with metals and can act as model systems for natural bio-inorganic compounds [2]. A considerable series (twelve novel compounds are reported) of 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp) and 5,7-diphenyl- 1,2,4-triazolo[1,5-a]pyrimidine (dptp) were synthesized and investigated by FT-IR and 119Sn M\uf6ssbauer in the solid state and by 1H and 13C NMR spectroscopy, in solution [3]. The X-ray crystal and molecular structures of Et2SnCl2(dbtp)2 and Ph2SnCl2(EtOH)2(dptp)2 were described, in this latter pyrimidine molecules are not directly bound to the metal center but strictly H-bonded, through N(3), to the -OH group of the ethanol moieties. The network of hydrogen bonding and aromatic interactions involving pyrimidine and phenyl rings in both complexes drives their self-assembly. Noncovalent interactions involving aromatic rings are key processes in both chemical and biological recognition, contributing to overall complex stability and forming recognition motifs. It is noteworthy that in Ph2SnCl2(EtOH)2(dptp)2 \u3c0\u2013\u3c0 stacking interactions between pairs of antiparallel triazolopyrimidine rings mimick basepair interactions physiologically occurring in DNA (Fig.1). M\uf6ssbauer spectra suggest for Et2SnCl2(dbtp)2 a distorted octahedral structure, with C-Sn-C bond angles lower than 180\ub0. The estimated angle for Et2SnCl2(dbtp)2 is virtually identical to that determined by X-ray diffraction. Ph2SnCl2(EtOH)2(dptp)2 is characterized by an essentially linear C-Sn-C fragment according to the X-ray all-trans structure. The compounds were screened for their in vitro antibacterial activity on a group of reference staphylococcal strains susceptible or resistant to methicillin and against two reference Gramnegative pathogens [4] . We tested the biological activity of all the specimen against a group of staphylococcal reference strains (S. aureus ATCC 25923, S. aureus ATCC 29213, methicillin resistant S. aureus 43866 and S. epidermidis RP62A) along with Gram-negative pathogens (P. aeruginosa ATCC9027 and E. coli ATCC25922). Ph2SnCl2(EtOH)2(dptp)2 showed good antibacterial activity with a MIC value of 5 \u3bcg mL-1 against S. aureus ATCC29213 and also resulted active against methicillin resistant S. epidermidis RP62A