Zhiyun Zhang

Bio: Zhiyun Zhang is an academic researcher from Northwest A&F University. The author has contributed to research in topics: Surface modification & Methacrylate. The author has an hindex of 4, co-authored 4 publications receiving 276 citations. Previous affiliations of Zhiyun Zhang include Laboratory of Molecular Biology.

Atomic force microscope study of tumor cell membranes following treatment with anti-cancer drugs

Abstract: Integrity of the cell membrane is a basic requirement for maintaining the biological characteristics of a cell. In this study, changes in the morphology and ultrastructure of HeLa (human cervical carcinoma), HepG2 (human hepatocellular liver carcinoma), and C6 (rat glioma) cells were studied by atomic force microscopy (AFM) both before and after treatment with the anti-cancer drugs, colchicine or cytarabine. In response to both drugs, the microstructure of the cell membrane of all three cell types displayed similar changes; that is, with increases in drug concentration and reaction time, the degree of morphological changes on the surface of cell membrane increased. These changes included increases in the fluctuation of the surface components of the cell membrane, increase in shrinkage, or even the appearance of pores. Cell viability was maintained, as determined by optical microscope observation of gross cell morphology and by MTT assay results. Analysis of the cell membrane root-mean-square (RMS) roughness showed that under the action of colchicine and cytarabine, RMS values for the cell membranes of all three tumor cell types were positively correlated to the drug concentration and reaction time. This research has great significance for the visual diagnosis of early stage apoptosis in tumor cells in response to anti-cancer drugs, as well as in the studies on the interaction between drugs and cells. The use of AFM can be a rapid and sensitive visual method for studying the interaction between cells and drug.

Surface modification of PDMS by surface-initiated atom transfer radical polymerization of water-soluble dendronized PEG methacrylate.

Abstract: The current paper reports the synthesis of a highly hydrophilic, antifouling dendronized poly(3,4,5-tris(2-(2-(2-hydroxylethoxy)ethoxy)ethoxy)benzyl methacrylate) (PolyPEG) brush using surface initiated atom transfer radical polymerization (SI-ATRP) on PDMS substrates. The PDMS substrates were first oxidized in H 2 SO 4 /H 2 O 2 solution to transform the Si–CH 3 groups on their surfaces into Si–OH groups. Subsequently, a surface initiator for ATRP was immobilized onto the PDMS surface, and PolyPEG was finally grafted onto the PDMS surface via copper-mediated ATRP. Various characterization techniques, including contact angle measurements, attenuated total reflection infrared spectroscopy, and X-ray photoelectron spectroscopy, were used to ascertain the successful grafting of the PolyPEG brush onto the PDMS surface. Furthermore, the wettability and stability of the PDMS–PolyPEG surface were examined by contact angle measurements. Anti-adhesion properties were investigated via protein adsorption, as well as bacterial and cell adhesion studies. The results suggest that the PDMS–PolyPEG surface exhibited durable wettability and stability, as well as significantly anti-adhesion properties, compared with native PDMS surfaces. Additionally, our results present possible uses for the PDMS–PolyPEG surface as adhesion barriers and anti-fouling or functional surfaces in biomedical applications.

High-throughput microfluidic system for long-term bacterial colony monitoring and antibiotic testing in zero-flow environments.

Abstract: In this study, a high-throughput microfluidic system is presented. The system is comprised of seven parallel channels. Each channel contains 32 square-shaped microchambers. After simulation studies on samples loaded into the microchambers, and the solute exchange between the microchambers and channels, the long-term culture of Escherichia coli (E. coli) HB101 in the microchambers is realized. Using the principle that l -arabinose ( l -Ara) can induce recombinant E. coli HB101 pGLO to synthesize green fluorescent protein (GFP), the real-time analysis of GFP expression in different initial bacterial densities is performed. The results demonstrate that higher initial loading densities of the bacterial colony cause bacterial cell to enter log-phase proliferation sooner. High or low initial loading densities of the bacterial cell suspension induce the same maximum growth rates during the log-phase. Quantitative on-chip analysis of tetracycline and erythromycin inhibition on bacterial cell growth is also conducted. Bacterial morphology changes during antibiotic treatment are observed. The results show that tetracycline and erythromycin exhibit different inhibition activities in E. coli cells. Concentrations of 3 μg/mL tetracycline can facilitate the formation of long filamentous bacteria with the average length of more than 50 μm. This study provides an on-chip framework for bacteriological research in a high-throughput manner and the development of recombinant bacteria-based biosensors for the detection of specific substances.

Photocatalyzed surface modification of poly(dimethylsiloxane) with polysaccharides and assay of their protein adsorption and cytocompatibility.

Abstract: An improved approach for the surface modification of poly(dimethylsiloxane) (PDMS) using carboxymethyl cellulose (CMC), carboxymethyl β-1,3-dextran (CMD), and alginic acid (AA) was investigated. The PDMS substrates were first oxidized in a H2SO4/H2O2 solution to transform the Si−CH3 groups on their surfaces into Si−OH groups. Then methacrylate groups were grafted onto the substrates through a silanization reaction using 3-(trimethoxysilyl)propyl methacrylate. Sequentially, cysteamine was conjugated onto the silanized surfaces by the reaction between the thiol and methacrylate groups under 254 nm UV exposure. Afterward, the amino-terminated PDMS substrates were sequentially reacted with CMC, CMD, and AA in the presence of N-hydroxysuccinimide and 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide, resulting in the grafting of polysaccharides onto PDMS surfaces. The composition and chemical state of the modified surfaces were characterized by X-ray photoelectron spectroscopy (XPS). In addition, the stability a...

Advantages and challenges of microfluidic cell culture in polydimethylsiloxane devices.

Abstract: Culture of cells using various microfluidic devices is becoming more common within experimental cell biology. At the same time, a technological radiation of microfluidic cell culture device designs is currently in progress. Ultimately, the utility of microfluidic cell culture will be determined by its capacity to permit new insights into cellular function. Especially insights that would otherwise be difficult or impossible to obtain with macroscopic cell culture in traditional polystyrene dishes, flasks or well-plates. Many decades of heuristic optimization have gone into perfecting conventional cell culture devices and protocols. In comparison, even for the most commonly used microfluidic cell culture devices, such as those fabricated from polydimethylsiloxane (PDMS), collective understanding of the differences in cellular behavior between microfluidic and macroscopic culture is still developing. Moving in vitro culture from macroscopic culture to PDMS based devices can come with unforeseen challenges. Changes in device material, surface coating, cell number per unit surface area or per unit media volume may all affect the outcome of otherwise standard protocols. In this review, we outline some of the advantages and challenges that may accompany a transition from macroscopic to microfluidic cell culture. We focus on decisive factors that distinguish macroscopic from microfluidic cell culture to encourage a reconsideration of how macroscopic cell culture principles might apply to microfluidic cell culture.

Advances in microfluidic materials, functions, integration, and applications.

Abstract: Microfluidics consist of microfabricated structures for liquid handling, with cross-sections in the 1–500 μm range, and small volume capacity (fL-nL) Capillary tubes connected with fittings,1 although utilizing small volumes, are not considered microfluidics for the purposes of this paper since they are not microfabricated Likewise, millifluidic systems, made by conventional machining tools, are excluded due to their larger feature sizes (>500 μm) Though micromachined systems for gas chromatography were introduced in the 1970’s,2 the field of microfluidics did not gain much traction until the 1990’s3 Silicon and glass were the original materials used, but then the focus shifted to include polymer substrates, and in particular, polydimethylsiloxane (PDMS) Since then the field has grown to encompass a wide variety of materials and applications The successful demonstration of electrophoresis and electroosmotic pumping in a microfluidic device provided a nonmechanical method for both fluid control and separation4 Laser induced fluorescence (LIF) enabled sensitive detection of fluorophores or fluorescently labeled molecules The expanded availability of low-cost printing allowed for cheaper and quicker mask fabrication for use in soft lithography5 Commercial microfluidic systems are now available from Abbott, Agilent, Caliper, Dolomite, Micralyne, Microfluidic Chip Shop, Micrux Technologies and Waters, as a few prominent examples For a more thorough description of the history of microfluidics, we refer the reader to a number of comprehensive, specialized reviews,3, 6–11 as well as a more general 2006 review12 The field of microfluidics offers many advantages compared to carrying out processes through bulk solution chemistry, the first of which relates to a lesson taught to every first-year chemistry student Simply stated, diffusion is slow! Thus, the smaller the distance required for interaction, the faster it will be Smaller channel dimensions also lead to smaller sample volumes (fL-nL), which can reduce the amount of sample or reagents required for testing and analysis Reduced dimensions can also lead to portable devices to enable on-site testing (provided the associated hardware is similarly portable) Finally, integration of multiple processes (like labeling, purification, separation and detection) in a microfluidic device can be highly enabling for many applications Microelectromechanical systems (MEMS) contain integrated electrical and mechanical parts that create a sensor or system Applications of MEMS are ubiquitous, including automobiles, phones, video games and medical and biological sensors13 Micro-total analysis systems, also known as labs-on-a-chip, are the chemical analogue of MEMS, as integrated microfluidic devices that are capable of automating multiple processes relevant to laboratory sciences For example, a typical lab-on-a-chip system might selectively purify a complex mixture (through filtering, antibody capture, etc), then separate target components and detect them Microfluidic devices consist of a core of common components Areas defined by empty space, such as reservoirs (wells), chambers and microchannels, are central to microfluidic systems Positive features, created by areas of solid material, add increased functionality to a chip and can consist of membranes, monoliths, pneumatic controls, beams and pillars Given the ubiquitous nature of negative components, and microchannels in particular, we focus here on a few of their properties Microfluidic channels have small overall volumes, laminar flow and a large surface-to-volume ratio Dimensions of a typical separation channel in microchip electrophoresis (μCE) are: 50 μm width, 15 μm height and 5 cm length for a volume of 375 nL Flow in these devices is normally nonturbulent due to low Reynolds numbers For example, water flowing at 20°C in the above channel at 1 μL/min (222 cm/s) results in a Reynolds number of ~05, where <2000 is laminar flow Since flow is nonturbulent, mixing is normally diffusion-limited Small channel sizes also have a high surface-to-volume ratio, leading to different characteristics from what are commonly found in bulk volumes The material surface can be used to manipulate fluid movement (such as by electroosmotic flow, EOF) and surface interactions For a solution in contact with a charged surface, a double layer of charge is created as oppositely charged ions are attracted to the surface charges This electrical double layer consists of an inner rigid or Stern Layer and an outer diffuse layer An electrostatic potential known as the zeta potential is formed, with the magnitude of the potential decreasing as distance from the surface increases The electrical double layer is the basis for EOF, wherein an applied voltage causes the loosely bound diffuse layer to move towards an electrode, dragging the bulk solution along Charges on the exposed surface also exert a greater influence on the fluid in a channel as its size decreases Larger surface-to-volume ratios are more prone to nonspecific adsorption and surface fouling In particular, non-charged and hydrophobic microdevice surfaces can cause proteins in solution to denature and stick We focus our review on advances in microfluidic systems since 2008 In doing this, we occasionally must cover foundational work in microfluidics that is considerably less recent We do not focus on chemical synthesis applications of microfluidics although it is an expanding area, nor do we delve into lithography, device fabrication or production costs Our specific emphasis herein is on four areas within microfluidics: properties and applications of commonly used materials, basic functions, integration, and selected applications For each of these four topics we provide a concluding section on opportunities for future development, and at the end of this review, we offer general conclusions and prospective for future work in the field Due to the considerable scope of the field of microfluidics, we limit our discussion to selected examples from each area, but cite in-depth reviews for the reader to turn to for further information about specific topics We also refer the reader to recent comprehensive reviews on advances in lab-on-a-chip systems by Arora et al10 and Kovarik et al14

Surface-Initiated Controlled Radical Polymerization: State-of-the-Art, Opportunities, and Challenges in Surface and Interface Engineering with Polymer Brushes

Abstract: The generation of polymer brushes by surface-initiated controlled radical polymerization (SI-CRP) techniques has become a powerful approach to tailor the chemical and physical properties of interfaces and has given rise to great advances in surface and interface engineering. Polymer brushes are defined as thin polymer films in which the individual polymer chains are tethered by one chain end to a solid interface. Significant advances have been made over the past years in the field of polymer brushes. This includes novel developments in SI-CRP, as well as the emergence of novel applications such as catalysis, electronics, nanomaterial synthesis and biosensing. Additionally, polymer brushes prepared via SI-CRP have been utilized to modify the surface of novel substrates such as natural fibers, polymer nanofibers, mesoporous materials, graphene, viruses and protein nanoparticles. The last years have also seen exciting advances in the chemical and physical characterization of polymer brushes, as well as an ev...

PDMS with designer functionalities—Properties, modifications strategies, and applications

Abstract: Rapid progress in micro- and nanotechnologies such as lab-on-a-chip (microfluidic networks, sensors, actuators, and connectors), soft lithography (replica moulding, microcontact printing and affinity contact printing), and stretchable transparent electronics has strongly benefitted from high-performance polymers like poly(dimethyl)siloxane (PDMS) that are suited for high-fidelity microsystem construction and rapid prototyping. While basic PDMS has been a unique enabling material, recent progress in tailoring PDMS to specific requirements will render this material even more valuable in the future. Basic PDMS is elastic, transparent, biocompatible, gas-permeable, and forms conformal contact with surfaces. Surface modifications of PDMS, inducing properties such as hydrophilicity, electrical conductivity, anti-fouling, energy harvesting, and energy storage (supercapacitors) are of major interest. Bulk modifications can alter PDMS properties such as elasticity, electrical and thermal conductivity. Such bulk modified PDMS composite materials can be created by embedding free molecules (e.g., dyes), nanoparticles (graphene, carbon nanotubes, and various other of organic and inorganic nature) or microparticles, or by altering the composition of the prepolymers before polymerization. Both, surface and bulk modifications of PDMS open avenues to a multitude of tuneable characteristics optimized for a diverse set of applications ranging from integrated micro- (lab-on-a-chip) to macro-systems (biomedical devices and epidermal electronics). In microfluidic systems design exploiting modified PDMS, a key aspect of this review, the unique features of these materials permit rapid, easy, and reproducible construction without the need for elaborate facilities and trained personnel as compared to other materials like silicon. This review focuses on recent progress in modification strategies to alter deliberately PDMS surface and bulk properties, especially for microfluidic, biological, flexible electronics, e-skin, and self-healing applications.

Anti-fouling Coatings of Poly(dimethylsiloxane) Devices for Biological and Biomedical Applications

Abstract: Fouling initiated by nonspecific protein adsorption is a great challenge in biomedical applications, including biosensors, bioanalytical devices, and implants Poly(dimethylsiloxane) (PDMS), a popular material with many attractive properties for device fabrication in the biomedical field, suffers serious fouling problems from protein adsorption due to its hydrophobic nature, which limits the practical use of PDMS-based devices Effort has been made to develop biocompatible materials for anti-fouling coatings of PDMS In this review, typical nonfouling materials for PDMS coatings are introduced and the associated basic anti-fouling mechanisms, including the steric repulsion mechanism and the hydration layer mechanism, are described Understanding the relationships between the characteristics of coating materials and the accompanying anti-fouling mechanisms is critical for preparing PDMS coatings with desirable anti-fouling properties