We introduce a microfluidic system for simultaneously measuring single cell mass and cell cycle progression over multiple generations. We use this system to obtain over 1,000 hours of growth data from mouse lymphoblast and pro-B-cell lymphoid cell lines. Cell lineage analysis revealed a decrease in the growth rate variability at the G1/S phase transition, which suggests the presence of a growth rate threshold for maintaining size homeostasis.

Direct observation of mammalian cell growth and size regulation

Nano-drug delivery systems (NDDS) are functional drug-loaded nanocarriers extensively applied in the healthcare and pharmaceutical areas. Recently, microfluidics has been demonstrated as one of the most promising techniques to fabricate high-performance NDDS with uniform morphology, size and size distribution, reduced batch-to-batch variations and controllable drug delivering capacity. Here, a brief review of the microfluidic-mediated NDDS is presented. The fundamentals of microfluidics are first interpreted with an emphasis on the fluid characteristics, design and materials for microfluidic devices. Then a comprehensive and in-depth depiction of the microfluidic-mediated fabrications of controllable NDDS with well-tailored internal structures and integrated functions for controlled encapsulation and drug release are categorized and reviewed, with particular descriptions about the underlying formation mechanisms. Afterwards, recently appreciated representative applications of the microfluidic-mediated NDDS for delivering multiple drugs are systematically summarized. Finally, conclusions and perspectives on further advancing the microfluidic-mediated NDDS toward more powerful and versatile platforms for therapeutic applications are discussed.

Microfluidic-mediated nano-drug delivery systems: from fundamentals to fabrication for advanced therapeutic applications

Microfluidics has become recognized as a powerful platform technology with a wide range of applications in various fields, such as biology, biomedicine, chemistry and environment To achieve higher performance, microfluidic devices are required to have superior optical transparency; mechanical, chemical and thermal stability; as well as easy design and fabrication All of these requirements make glass as an attractive and ideal material for the fabrication of microfluidic devices due to its excellent characteristics in optical, mechanical, thermal, electrical and chemical aspects in comparison to other materials (eg, silicon and polydimethylsiloxane) In order to give preliminary guidance for researchers from different backgrounds, we provide a comprehensive overview of the fabrication methods for glass-based microfluidic devices as well as various applications based on different types of glass This review takes into account recent advances in the fabrication of microfluidics, such as, liquid glass and ultra-thin glass, so as to provide a full understanding of the latest research trend in this area Finally, some remaining challenges facing the field are summarized, and potential prospects for future work with an emphasis on both emerging techniques are discussed

Glass based micro total analysis systems: Materials, fabrication methods, and applications

Organic-based flexible thermoelectric generators: from materials to devices

Organic-based flexible thermoelectric generators: From materials to devices

Glass is a common material used in various microsystems including sensors, actuators, and microfluidic devices due to its extraordinary properties. However, lack of flexibility and elasticity limits its potential for further applications. To solve this issue, thinning the thick glass plate to a few microns is a solution. However, conventional methods for thinning thick glass plates are complex, risky, time-consuming, and difficult for implementation at the laboratory level. This paper reports an efficient and convenient fabrication method for an independent ultra-thin glass sheet (UTGS) (≤ 3 μm, the world’s thinnest) by utilizing a weight-controlled load-assisted (WCL-assisted) thermal stretching. Unlike other methods requiring a full melting of the glass material, the key point of the proposed method is using a WCL to precisely stretch a commercial thick glass plate to achieve the desired glass sheet thickness. To fabricate UTGSs of the desired thicknesses, experimental conditions including temperatures (630°C–700°C), cooling times (1.5 h–2.5 h), and weights of loads (1 g–9 g) were investigated. Furthermore, the potential advantage of using the fabricated UTGS for indicator applications in micro-systems was proven by fabricating a pressure indicator having higher sensitivity than presently available devices. For the same working conditions, the maximum sensitivity of the new indicator was improved by 86.8 % compared with the sensitivity previously obtained.

Fabrication of ultra-thin glass sheet by weight-controlled load-assisted precise thermal stretching

We demonstrated a self-driven chemical micropump powered by self-oscillating motions of synthetic polymer gel converting chemical energy into displacements of a thin polydimethylsiloxane (PDMS) sheet to produce a directional flow via micro check valves. The gel oscillations induced by the oscillatory Belousov-Zhabotinsky (BZ) reaction generate large volume change. To effectively exploit this volume change, gel bars were used as drivers. They were sandwiched by a fixed cover glass and a push-bar to communicate the expanding (pushing) force of the gel bars to the pumping chamber. At 25 °C, this gel micropump generated a 0.07 mN stroke force and a 0.28 μL/min positive net flow in the microchannel. Additionally, the flow rate of this gel micropump was increased as the temperature was raised from 20 to 30 °C. Compared to existing chemical micropumps, this gel-based micropump provides advantages of self-oscillating property, easy refueling and thermal controllability. This gel-based soft micropump would be used as wearable or medical devices exploiting the flexibility and quietness.

A chemical micropump actuated by self-oscillating polymer gel

Contactless particle manipulation based on a thermal field has shown great potential for biological, medical, and materials science applications. However, thermal diffusion from a high-temperature area causes thermal damage to bio-samples. Besides, the permanent bonding of a sample chamber onto microheater substrates requires that the thermal field devices be non-disposable. These limitations impede use of the thermal manipulation approach. Here, a novel manipulation platform is proposed that combines microheaters and an area cooling system to produce enough force to steer sedimentary particles or cells and to limit the thermal diffusion. It uses the one-time fabricated motherboard and an exchangeable sample chamber that provides disposable use. Sedimentary objects can be steered to the bottom center of the thermal field by combined thermal convection and thermophoresis. Single particle or cell manipulation is realized by applying multiple microheaters in the platform. Results of a cell viability test confirmed the method's compatibility in biology fields. With its advantages of biocompatibility for live cells, operability for different sizes of particles and flexibility of platform fabrication, this novel manipulation platform has a high potential to become a powerful tool for biology research.

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Area cooling enables thermal positioning and manipulation of single cells

We present an efficient fabrication technique for a glass microdome structure (GMDS) based on the microthermal expansion principle, by inflating the microcavities confined between two thin glass slides. This technique allows controlling the height, diameter, and shape of the GMDS with a uniformity under 5%. The GMDS has a high potential for the application of the microlens and lens array. This inflated hollow, thin glass structure is stable at extreme environments such as in strong acid and high temperature conditions. More importantly, the hollow microdome can be filled with liquid substances to further extend its applications. To verify our method, various GMDSs were fabricated under different process conditions, at different temperatures (540 °C–600 °C), microcavity diameters (300 μm–600 μm), glass thicknesses (120 μm–240 μm), and microcavity etching depths (25 μm–70 μm). The optical features of “empty” and “filled” microcavities were investigated. An empty microcavity functioned as a reducing lens (0.61×–0.9×) (meniscus lens), while a filled microcavity functioned as a magnifying lens (1.31×–1.65×) (biconvex lens). In addition, both lenses worked in strong acid (sulfuric acid) and high temperature (over 300 °C) conditions in which other materials of lenses cannot be used.

Thin glass micro-dome structure based microlens fabricated by accurate thermal expansion of microcavities

We report an on-chip single-cell multidirectional observation method by accurately control the ultra-thin glass chamber rotation angles over the microscope. This technique enables to establish the multidirectional visual accesses to the target cell that captured inside of the thin glass chamber. The ultra-thin glass chamber has advantages of highly transparent, compact, thin wall, less invasive and all-closed structures efficiently reduces the risks of contamination during the observation. The fabricated thin glass chambers diameters were different from 1.5 to 3.5 mm which formed on the 200 μm glass slides.

Yusufu Aishan

Papers

Fabrication of ultra-thin glass sheet by weight-controlled load-assisted precise thermal stretching

A chemical micropump actuated by self-oscillating polymer gel

Area cooling enables thermal positioning and manipulation of single cells

Thin glass micro-dome structure based microlens fabricated by accurate thermal expansion of microcavities

Accurate rotation of ultra-thin glass chamber for single-cell multidirectional observation