Nanjing Hao

Roles of particle size, shape and surface chemistry of mesoporous silica nanomaterials on biological systems

The successful application of mesoporous silica nanomaterials (MSNs) in biomedical fields requires careful consideration of their spatial dimensions, biofunctionality, specific cellular uptake efficiency, biocompatibility and targeting delivery efficacy. A deep understanding of the interactions between MSNs and biological systems is thus of significant importance. To this end, over the past few decades, studies aimed at synthesis of MSNs with controlled size, shape and surface chemistry properties and exploring the roles of these properties on in vitro and in vivo biological performance have been conducted. These studies provide new and foundational information for engineering the next generation of mesoporous silica-based nanoscale devices. This review highlights the current progress on the controlled synthesis of size, shape and surface chemistry tuneable MSNs, emphasises the roles of size, shape and surface chemistry on biological systems with a special focus on the direct comparison studies, and discusses the emerging design paradigm for building mesoporous silica-based particulate systems.

Microfluidic Screening of Circulating Tumor Biomarkers toward Liquid Biopsy

The development of early and personalized diagnostic protocol with rapid response and high accuracy is considered the most promising avenue to advance point-of-care testing for tumor diagnosis and therapy. Given the growing awareness of the limitations of conventional tissue biopsy for gathering tumor information, considerable interest has recently been aroused in liquid biopsy. Among a myriad of analytical approaches proposed for liquid biopsy, microfluidics-based separation and purification techniques possess merits of high throughput, low samples consumption, high flexibility, low cost, high sensitivity, automation capability and enhanced spatio-temporal control. These characteristics endow microfluidics to serve as an emerging and promising tool in tumor diagnosis and prognosis by identifying specific circulating tumor biomarkers. In this review, we will put our focus on three key categories of circulating tumor biomarkers, namely, circulating tumor cells (CTCs), circulating exosomes, and circulating nucleic acids (cNAs), and discuss the significant roles of microfluidics in the separation and analysis of circulating tumor biomarkers. Recent advances in microfluidic separation and analysis of CTCs, exosomes, and cNAs will be highlighted and tabulated. Finally, the current challenges and future niches of using microfluidic techniques in the separation and analysis of circulating tumor biomarkers will be discussed.

Microfluidics-mediated self-template synthesis of anisotropic hollow ellipsoidal mesoporous silica nanomaterials

ABSTRACT Herein, a facile strategy was firstly developed to synthesize ellipsoidal mesoporous silica nanomaterials (MSNs) with well-ordered parallel channels along the short axis. A miniaturized microfluidic device with spiral-shaped channels was then chosen as a straightforward and general platform to produce the corresponding hollow counterparts of MSNs under mild conditions. Such reaction process carried out in a microfluidic system was further demonstrated to be more rapid and efficient than a conventional batch method under equivalent experimental conditions. The evolution of hollow structure can be well tuned by flow rates (i.e. etching time), providing a new paradigm for rational design and engineering of anisotropic nanostructures. GRAPHICAL ABSTRACT IMPACT STATEMENT This study developed a straightforward and general microfluidic platform to produce hollow nanostructures, providing new routes for rational design and engineering of functional nanomaterials.

Biomimetic hierarchical walnut kernel-like and erythrocyte-like mesoporous silica nanomaterials: Controllable synthesis and versatile applications

We developed a facile and controllable strategy to fabricate biomimic walnut kernel-like mesoporous silica nanomaterial (WMSN) and erythrocyte-like mesoporous silica nanomaterial (EMSN). The former possesses unique multi-shell hollow structure and surface wrinkles while the latter has special multi-stack structure and bowl-shaped depression. These hierarchical materials with distinct structures can be finely tuned by changing the molar ratios of two surfactants, cetyltrimethylammonium bromide and 11-mercaptoundecanoic acid. The mechanism of structural formation through intermolecular interactions was revealed and validated experimentally. The promising potential applications of WMSN and EMSN in adsorption, cellular imaging, drug delivery, and cancer theranostics were further identified.

Ultrafast Synthesis of Multifunctional Submicrometer Hollow Silica Spheres in Microfluidic Spiral Channels

We demonstrate a facile and ultrafast approach for the synthesis of multifunctional submicrometer hollow silica spheres (smHSSs) using microfluidic spiral channels with enhanced mixing performance, introduced by the transverse Dean flows cross the channel as a result of centrifugal effects. Formation of smHSSs is initiated by the hydrolysis of tetraethyl orthosilicate (TEOS) at the interface of two laminar reactant flows. Complete mixing of the flows further facilitates the subsequent condensation of hydrolyzed TEOS, which builds up the shell layer of smHSSs. The average size of the as-synthesized smHSSs is 804.7 nm, and the thickness of the shell layer is ~20 nm. Multifunctional smHSSs integrated with proteins, fluorescent dyes, quantum dots, and magnetic nanoparticles can be further produced via this general platform. Their applications in cell imaging, organic dye adsorption, and drug delivery are examined.

Microfluidic synthesis of functional inorganic micro-/nanoparticles and applications in biomedical engineering

ABSTRACT Engineered micro-/nanoparticles of various physicochemical properties play significant roles in biomedical engineering from biosensing, in vivo imaging, in vitro diagnosis, drug delivery to therapy. Compared to conventional batch synthesis, microfluidics-based synthesis enables precise reaction control, enhanced mixing, and rapid chemical reactions, allowing for the flow synthesis of particles in a controllable, sustainable, and costsaving manner that is attractive to industry. This review focuses on the recent advances of using microfluidic devices for the flow synthesis of inorganic micro-/nanoparticles with specific properties and their practical applications. We highlight the principle and the merits of emerging microfluidic techniques over conventional methods, discuss chemical reactions performed in the microfluidic reactors, summarize and tabulate strategies for the flow synthesis of inorganic particles, and provide the established applications of materials from these microfluidic systems. The challenges, opportunities, and future perspectives of microfluidics in the synthesis and applications of inorganic micro-/nanoparticles are furthermore discussed.

Microfluidics-enabled rapid manufacturing of hierarchical silica-magnetic microflower toward enhanced circulating tumor cells screening

The emergence of microfluidic techniques provides new opportunities for chemical synthesis and biomedical applications. Herein, we first develop a microfluidics-based flow and sustainable strategy to synthesize hierarchical silica-magnetic microflower with unique multilayered structure for the efficient capture of circulating tumor cells through our engineered microfluidic screening chip. The production of microflower materials can be realized within 94 milliseconds and a yield of nearly 5 grams per hour can be achieved. The enhanced bioaccessibility of such a multilayered microflower towards cancer cells (MCF-7 and MDA-MB-231) is demonstrated, and the cancer cell capture efficiency of this hierarchical immunomagnetic system in clinical blood samples is significantly increased compared with a standard CellSearch™ assay. These findings bring new insights for engineering functional micro-/nanomaterials in liquid biopsy.

Tunable Buckled Beams with Mesoporous PVDF-TrFE/SWCNT Composite Film for Energy Harvesting

By incorporating mesoporous piezoelectric materials and tuning mechanical boundary conditions a simple beam structure can significantly take advantage of limited mechanical displacements for energy harvesting. Specifically, we employed a mesoporous PVDF-TrFE composite thin film mixed with single-wall carbon nanotubes to improve the formation of the crystalline phase in this piezoelectric polymer. The film was then patterned on a thin buckled beam to form a compact energy harvester, which was used to study the effects of two boundary conditions, including the end rotation angle and the location of a mechanical stop along the beam. We carefully designed controlled experiments using mesoporous PVDF-TrFE film and PVDF-TrFE/SWCNT composite films, both of which were tested under two cases of boundary conditions, namely, the rotation of the end angle and the addition of a mechanical stop. The voltage and current of the energy harvester under these two boundary conditions were, respectively, increased by approximately 160.1% and 200.5% compared to the results of its counterpart without imposing any boundary conditions. Thereby, our study offers a promising platform for efficiently powering implantable and wearable devices for harnessing energy from the human body which would otherwise have been wasted.