Tian Hang

Microfluidic Fabrication of Colloidal Nanomaterials-Encapsulated Microcapsules for Biomolecular Sensing

Implantable sensors that detect biomarkers in vivo are critical for early disease diagnostics. Although many colloidal nanomaterials have been developed into optical sensors to detect biomolecules in vitro, their application in vivo as implantable sensors is hindered by potential migration or clearance from the implantation site. One potential solution is incorporating colloidal nanosensors in hydrogel scaffold prior to implantation. However, direct contact between the nanosensors and hydrogel matrix has the potential to disrupt sensor performance. Here, we develop a hollow-microcapsule-based sensing platform that protects colloidal nanosensors from direct contact with hydrogel matrix. Using microfluidics, colloidal nanosensors were encapsulated in polyethylene glycol microcapsules with liquid cores. The microcapsules selectively trap the nanosensors within the core while allowing free diffusion of smaller molecules such as glucose and heparin. Glucose-responsive quantum dots or gold nanorods or heparin-responsive gold nanorods were each encapsulated. Microcapsules loaded with these sensors showed responsive optical signals in the presence of target biomolecules (glucose or heparin). Furthermore, these microcapsules can be immobilized into biocompatible hydrogel as implantable devices for biomolecular sensing. This technique offers new opportunities to extend the utility of colloidal nanosensors from solution-based detection to implantable device-based detection.

Physical activation of innate immunity by spiky particles

Microbial biochemicals have been indicated as the primary stimulators of innate immunity, the first line of the body’s defence against infections. However, the influence of topological features on a microbe’s surface on immune responses remains largely unknown. Here we demonstrate the ability of TiO2 microparticles decorated with nanospikes (spiky particles) to activate and amplify the immune response in vitro and in vivo. The nanospikes exert mechanical stress on the cells, which results in potassium efflux and inflammasome activation in macrophages and dendritic cells during phagocytosis. The spiky particles augment antigen-specific humoral and cellular immune responses in the presence of monophosphoryl lipid A and elicit protective immunity against tumour growth and influenza viral infection. The study offers insights into how surface physical cues can tune the activation of innate immunity and provides a basis for engineering particles with increased immunogenicity and adjuvanticity.Spikes on the surface of TiO2 microparticles, mimicking the nanotopological structures found on pathogens, boost the immune response in animal models and can be used to enhance the immunogenic effect of vaccines and adjuvants.

Nanospikes-mediated Anomalous Dispersities of Hydropobic Micro-objects and their Application for Oil Emulsion Cleaning

Many fields of applications require dispersion of hydrophobic particles in water, which is traditionally achieved by using surfactants or amphiphilic molecules to modify particle surfaces. However, surfactants or amphiphilic molecules may disturb the native solution or particles’ surface hydrophobicity, limiting extended applications such as oil emulsion cleaning. Recently one example of 2 μm-size polystyrene microparticles covered with ZnO nanospikes has been shown to exhibit excellent dispersity in water in spite of surface hydrophobicity. Whether this anomalous dispersion phenomenon was applicable to other hydrophobic microparticle systems was still unclear and its application scope was limited. Here the anomalous dispersities of different hydrophobic spiky micro-objects were systematically explored. The results show that the anomalous dispersion phenomenon was universally observed on different hydrophobic spiky micro-objects including different hydrophobic coating, particle sizes, material compositions and core particle morphologies. In addition, the spiky micro-objects displayed anomalous dispersity in water without compromising surface hydrophobicity, and their applications for oil spills absorption and oil emulsion cleaning were demonstrated. This work offers unique insight on the nanospikes-mediated anomalous dispersion phenomenon of hydrophobic micro-object and potentially extends its applicability and application scopes.

Nanospikes functionalization as a universal strategy to disperse hydrophilic particles in non-polar media

Dispersion of hydrophilic particles in non-polar media has many important applications yet remains difficult. Surfactant or amphiphilic functionalization was conventionally applied to disperse particles but is highly dependent on the particle/solvent system and may induce unfavorable effects and impact particle hydrophilic nature. Recently 2 μm size polystyrene microbeads coated with ZnO nanospikes have been reported to display anomalous dispersity in phobic media without using surfactant or amphiphilic functionalization. However, due to the lack of understanding whether this phenomenon was applicable to a wider range of conditions, little application has been derived from it. Here the anomalous dispersity phenomenons of hydrophilic microparticles covered with nanospikes were systematically assessed at various conditions including different particle sizes, material compositions, particle morphologies, solvent hydrophobicities, and surface polar groups. Microparticles were functionalized with nanospikes through hydrothermal route, followed by dispersity test in hydrophobic media. The results suggest nanospikes consistently prevent particle aggregation in various particle or solvent conditions, indicating the universal applicability of the anomalous dispersion phenomenons. This work provides insight on the anomalous dispersity of hydrophilic particles in various systems and offers potential application to use this method for surfactant-free dispersions.

Hollow Nanoneedle-Electroporation System To Extract Intracellular Protein Repetitively and Nondestructively

Techniques used to understand the dynamic expression of intracellular proteins are critical in both fundamental biological research and biomedical engineering. Various methods for analyzing proteins have been developed, but these methods require the extraction of intracellular proteins from the cells resulting in cell lysis and subsequent protein purifications from the lysate, which limits the potential of repetitive extraction from the same set of viable cells to track dynamic intracellular protein expression. Therefore, it is crucial to develop novel methods that enable nondestructive and repeated extraction of intracellular proteins. This work reports a hollow nanoneedle-electroporation system for the repeated extraction of intracellular proteins from living cells. Hollow nanoneedles with ∼450 nm diameter were fabricated by a material deposition and etching process, followed by integration with a microfluidic device. Long-lasting electrical pulses were coupled with the nanoneedles to permeate the cell membrane, allowing intracellular contents to diffuse into the microfluidic channels located below the cells via hollow nanoneedles. Using lactate dehydrogenase B (LDHB) as the model intracellular protein, the nanoneedle-electroporation system effectively and repeatedly extracted LDHB from the same set of cells at different time points, followed by quantitative analysis of LDHB via standard enzyme-linked immunosorbent assay. Our work demonstrated an efficient method to nondestructively probe intracellular protein levels and monitor the dynamic protein expression, with great potential to help understanding cell behaviors and functions.

TiO2 nanowire-templated hierarchical nanowire network as water-repelling coating

Extraordinary water-repelling properties of superhydrophobic surfaces make them novel candidates for a great variety of potential applications. A general approach to achieve superhydrophobicity requires low-energy coating on the surface and roughness on nano- and micrometre scale. However, typical construction of superhydrophobic surfaces with micro-nano structure through top-down fabrication is restricted by sophisticated fabrication techniques and limited choices of substrate materials. Micro-nanoscale topographies templated by conventional microparticles through surface coating may produce large variations in roughness and uncontrollable defects, resulting in poorly controlled surface morphology and wettability. In this work, micro-nanoscale hierarchical nanowire network was fabricated to construct self-cleaning coating using one-dimensional TiO2 nanowires as microscale templates. Hierarchical structure with homogeneous morphology was achieved by branching ZnO nanowires on the TiO2 nanowire backbones through hydrothermal reaction. The hierarchical nanowire network displayed homogeneous micro/nano-topography, in contrast to hierarchical structure templated by traditional microparticles. This hierarchical nanowire network film exhibited high repellency to both water and cell culture medium after functionalization with fluorinated organic molecules. The hierarchical structure templated by TiO2 nanowire coating significantly increased the surface superhydrophobicity compared to vertical ZnO nanowires with nanotopography alone. Our results demonstrated a promising strategy of using nanowires as microscale templates for the rational design of hierarchical coatings with desired superhydrophobicity that can also be applied to various substrate materials.