Magnetic nanochain integrated microfluidic biochips.
ABSTRACT: Microfluidic biochips hold great potential for liquid analysis in biomedical research and clinical diagnosis. However, the lack of integrated on-chip liquid mixing, bioseparation and signal transduction presents a major challenge in achieving rapid, ultrasensitive bioanalysis in simple microfluidic configurations. Here we report magnetic nanochain integrated microfluidic chip built upon the synergistic functions of the nanochains as nanoscale stir bars for rapid liquid mixing and as capturing agents for specific bioseparation. The use of magnetic nanochains enables a simple planar design of the microchip consisting of flat channels free of common built-in components, such as liquid mixers and surface-anchored sensing elements. The microfluidic assay, using surface-enhanced Raman scattering nanoprobes for signal transduction, allows for streamlined parallel analysis of multiple specimens with greatly improved assay kinetics and delivers ultrasensitive identification and quantification of a panel of cancer protein biomarkers and bacterial species in 1??l of body fluids within 8?min.
Project description:To synthesize multi-component nanochains, we developed a simple 'one-pot' synthesis, which exhibited high yield and consistency. The nanochains particles consist of parent nanospheres chemically linked into a higher-order, chain-like assembly. The one-pot synthesis is based on the addition of two types of parent nanospheres in terms of their surface chemical functionality (e.g., decorated with PEG-NH2 or PEG-COOH). By reacting the two types of parent nanospheres at a specific ratio (?2?:?1) for a short period of time (?30 min) under rigorous stirring, nanochains were formed. For example, we show the synthesis of iron oxide nanochains with lengths of about 125 nm consisting of 3-5 constituting nanospheres. The chain-like shaped nanoparticle possessed a unique ability to target and rapidly deposit on the endothelium of glioma sites via vascular targeting. To target and image invasive brain tumors, we used iron oxide nanochains with the targeting ligand being the fibronectin-targeting peptide CREKA. Overexpression of fibronectin is strongly associated with the perivascular regions of glioblastoma multiforme and plays a critical role in migrating and invasive glioma cells. In mice with invasive glioma tumors, 3.7% of the injected CREKA-targeted nanochains was found in gliomas within 1 h. Notably, the intratumoral deposition of the nanochain was ?2.6-fold higher than its spherical variant. Using MR imaging, the precise targeting of nanochains to gliomas provided images with the exact topology of the disease including their margin of infiltrating edges and distant invasive sites.
Project description:Despite advancements in surgery and radiotherapy, the aggressive forms of brain tumors, such as gliomas, are still uniformly lethal with current therapies offering only palliation complicated by significant toxicities. Gliomas are characteristically diffuse with infiltrating edges, resistant to drugs and nearly inaccessible to systemic therapies due to the brain-tumor barrier. Currently, aggressive efforts are underway to further understand brain-tumor's microenvironment and identify brain tumor cell-specific regulators amenable to pharmacologic interventions. While new potent agents are continuously becoming available, efficient drug delivery to brain tumors remains a limiting factor. To tackle the drug delivery issues, a multicomponent chain-like nanoparticle has been developed. These nanochains are comprised of iron oxide nanospheres and a drug-loaded liposome chemically linked into a 100-nm linear, chain-like assembly with high precision. The nanochain possesses a unique ability to scavenge the tumor endothelium. By utilizing effective vascular targeting, the nanochains achieve rapid deposition on the vascular bed of glioma sites establishing well-distributed drug reservoirs on the endothelium of brain tumors. After reaching the target sites, an on-command, external low-power radiofrequency field can remotely trigger rapid drug release, due to mechanical disruption of the liposome, facilitating widespread and effective drug delivery into regions harboring brain tumor cells. Integration of the nanochain delivery system with the appropriate combination of complementary drugs has the potential to unfold the field and allow significant expansion of therapies for the disease where success is currently very limited. WIREs Nanomed Nanobiotechnol 2016, 8:678-695. doi: 10.1002/wnan.1387 For further resources related to this article, please visit the WIREs website.
Project description:Glioblastoma multiforme is generally recalcitrant to current surgical and local radiotherapeutic approaches. Moreover, systemic chemotherapeutic approaches are impeded by the blood-tumor barrier. To circumvent limitations in the latter area, we developed a multicomponent, chain-like nanoparticle that can penetrate brain tumors, composed of three iron oxide nanospheres and one drug-loaded liposome linked chemically into a linear chain-like assembly. Unlike traditional small-molecule drugs or spherical nanotherapeutics, this oblong-shaped, flexible nanochain particle possessed a unique ability to gain access to and accumulate at glioma sites. Vascular targeting of nanochains to the ?v?3 integrin receptor resulted in a 18.6-fold greater drug dose administered to brain tumors than standard chemotherapy. By 2 hours after injection, when nanochains had exited the blood stream and docked at vascular beds in the brain, the application of an external low-power radiofrequency field was sufficient to remotely trigger rapid drug release. This effect was produced by mechanically induced defects in the liposomal membrane caused by the oscillation of the iron oxide portion of the nanochain. In vivo efficacy studies conducted in two different mouse orthotopic models of glioblastoma illustrated how enhanced targeting by the nanochain facilitates widespread site-specific drug delivery. Our findings offer preclinical proof-of-concept for a broadly improved method for glioblastoma treatment.
Project description:Cancerous cells and the tumor microenvironment are among key elements involved in cancer development, progression, and resistance to treatment. In order to tackle the cells and the extracellular matrix, we herein propose the use of a class of silica-coated iron oxide nanochains, which have superior magnetic responsiveness and can act as efficient photothermal agents. When internalized by different cancer cell lines and normal (non-cancerous) cells, the nanochains are not toxic, as assessed on 2D and 3D cell culture models. Yet, upon irradiation with near infrared light, the nanochains become efficient cytotoxic photothermal agents. Besides, not only do they generate hyperthermia, which effectively eradicates tumor cells in vitro, but they also locally melt the collagen matrix, as we evidence in real-time, using engineered cell sheets with self-secreted extracellular matrix. By simultaneously acting as physical (magnetic and photothermal) effectors and chemical delivery systems, the nanochain-based platforms offer original multimodal possibilities for prospective cancer treatment, affecting both the cells and the extracellular matrix.
Project description:Proteins are macromolecules with characteristic structures and biological functions. It is extremely challenging to obtain protein microtube structures through self-assembly as proteins are very complex and flexible. Here we present a strategy showing how a specific protein, ADP-ribosyl cyclase, helically self-assembles from monomers into hexagonal nanochains and further to highly ordered crystalline microtubes. The structures of protein nanochains and consequently self-assembled superlattice were determined by X-ray crystallography at 4.5 A resolution and imaged by scanning electron microscopy. The protein initially forms into dimers that have a fixed size of 5.6 nm, and then, helically self-assembles into 35.6 nm long hexagonal nanochains. One such nanochain consists of six dimers (12 monomers) that stack in order by a pseudo P6(1) screw axis. Seven nanochains produce a series of large-scale assemblies, nanorods, forming the building blocks for microrods. A proposed aging process of microrods results in the formation of hollow microstructures. Synthesis and characterization of large scale self-assembled protein microtubes may pave a new pathway, capable of not only understanding the self-assembly dynamics of biological materials, but also directing design and fabrication of multifunctional nanobuilding blocks with particular applications in biomedical engineering.
Project description:Understanding the thermodynamic behavior and growth kinetics of colloidal nanoparticles (NPs) is essential to synthesize materials with desirable structures and properties. In this paper, we present specific uncapped Te colloidal NPs obtained through laser ablation of Te in various protic or aprotic solvents. At ambient temperature and pressure, the uncapped Te NPs spontaneously exhibited analogous evolution and growth of "nanoparticle-nanochain-agglomerate-microsphere" in different solvents. The distinctive growth kinetics of the formation of nanochains strongly depended on the polarity and dielectric constant of solvent molecules. The growth rate of agglomerates and microspheres was closely related to the zeta potential of the colloidal solution of Te nanochains and the average size of Te agglomerates. Furthermore, the resulting uncapped Te NPs and Te nanochains displayed a prominent size-dependent and structure-inherited chemical reductive ability. These findings provide insights into the growth of active uncapped nanoparticles in various dispersion media. This study also provides an alternative route in designing novel nanostructures of alloys, telluride, and functional composites using Te as a unique reactive precursor.
Project description:Localized surface plasmon resonance (LSPR) offers a valuable opportunity to improve the efficiency of photocatalysts. However, plasmonic enhancement of photoconversion is still limited, as most of metal-semiconductor building blocks depend on LSPR contribution of isolated metal nanoparticles. In this contribution, the concept of collective excitation of embedded metal nanoparticles is demonstrated as an effective strategy to enhance the utilization of plasmonic energy. The contribution of Au-nanochain to the enhancement of photoconversion is 3.5 times increase in comparison with that of conventional isolated Au nanoparticles. Experimental characterization and theoretical simulation show that strongly coupled plasmonic nanostructure of Au-nanochain give rise to highly intensive electromagnetic field. The enhanced strength of electromagnetic field essentially boosts the formation rate of electron-hole pair in semiconductor, and ultimately improves photocatalytic hydrogen evolution activity of semiconductor photocatalysts. The concept of embedded coupled-metal nanostructure represents a promising strategy for the rational design of high-performance photocatalysts.
Project description:Carbon-encapsulated LiFePO<sub>4</sub> (LFP) nanochains were prepared as a cathode material for lithium batteries by sol-gel method using citric acid as the carbon source. The prepared LFP/C material is characterized by structural, morphological, and electrochemical characterization. LFP/C shows an orthorhombic olivine structure with "<i>Pnma</i>" space group having an average particle size of 50 nm. The uniform distribution of LFP particles coated by the carbon matrix as a nanochain array has been analyzed by scanning electron microscopy and transmission electron microscopy analysis of the sample. The electrochemical performance of the LFP/C nanochain has been analyzed using galvanostatic cycling, cyclic voltammetry, and impedance analysis of the assembled batteries. The sol-gel-derived LFP/C nanochain exhibits better capacity and electrochemical reversibility in line with the literature results. The high-temperature conductivity profile of the sample has been recorded from room temperature to 473 K using impedance analysis of the sample. The transport dynamics have been analyzed using the dielectric and modulus spectra of the sample. A maximum conductivity up to 6.74 × 10<sup>-4</sup> S cm<sup>-1</sup> has been obtained for the samples at higher temperature (448 K). The nucleation and growth at higher temperature act as factors to facilitate the intermediate phase existence in the LiFePO<sub>4</sub> sample in which the phase change that occurs above 400 K gives irreversible electrochemical changes in the LFP/C samples.
Project description:Designing Pt-based alloy catalysts with multicomponent composition and a controllable structure is important to improve the utilization efficiency of precious metals and catalytic activity, but it still face a lot of challenges for simple preparation. Herein, we used insulin amyloid fibrils as templates and their own one-dimensional spiral structure to synthesize Pt-Rh-Pd ternary alloy nanochains under mild conditions. The prepared Pt-Rh-Pd alloy nanochains (NCs) have uniform diameter, and the particle size is only 2 nm. This ultrafine structure increases the specific surface area of the catalyst to a certain extent, and the synergistic effect of the three metals improves the catalytic performance. Compared with commercial Pt/C and binary Pt-Rh NCs, the as-presented Pt-Rh-Pd NCs show better methanol oxidation activity ability and stability against CO poisoning. The peak current density of front sweep is 1.48 mA cm<sup>-2</sup>, which is 1.7 times higher than that of commercial Pt/C (0.89 mA cm<sup>-2</sup>) and 1.4 times higher than that of the Pt-Rh NCs (1.07 mA cm<sup>-2</sup>), indicating great application potential as high-performance electrocatalysts in fuel cells.
Project description:An air venting element on microchannel, which can be controlled externally and automatically, was demonstrated for manipulating liquid plugs in microfluidic systems. The element's open and closed statuses correspond to the positioning and movement of a liquid plug in the microchannel. Positioning of multiple liquid plugs at an air venting element enabled the merging and mixing of the plugs. Besides these basic functions, other modes of liquid plug manipulations including plug partitioning, multiple plug mixing, and spacing adjustment between liquid plugs, were realized using combination of multiple elements. The structure, operation, and some functions of the element were demonstrated with a microfluidic chip application. The performances of the element including its failure modes, threshold flow rate, and structural optimization were also discussed.