"Plug and Play" logic gate construction based on chemically triggered fluorescence switching of gold nanoparticles conjugated with Cy3-tagged aptamer.

Gold nanoparticles (AuNPs) conjugated with Cy3-tagged aptamer which can specifically recognize chloramphenicol (CAP) (referred to as AuNPs-AptCAP) are described. CAP can trigger the configuration change of CAP binding aptamer, and thus switching the fluorescence of AuNPs-AptCAP through changing the efficiency of the fluorescence resonance energy transfer (FRET) system with Cy3 as donors and AuNPs as recipients. AuNPs-AptCAP exhibits a linear range of CAP concentrations from 26.

Facile synthesis and functionalization of color-tunable Ln-doped KGdF nanoparticles on a microfluidic platform.

Hyaluronic acid (HA)-functionalized lanthanide-doped KGdF nanoparticles were synthesized through two steps on a microfluidic platform. This microfluidic synthesis method allows better control of experimental conditions with lower labor and energy input than traditional beaker synthesis methods for large-scale production of nanoparticles with higher uniformity. First, Ln-doped KGdF nanoparticles were ultrafast (in minutes) and continuously synthesized using a four-inlets microfluidic chip at room temperature.

Recent advances in microfluidic technology for manipulation and analysis of biological cells (2007-2017).

The pivotal role of microfluidic technology in life science and biomedical research is now widely recognized. Indeed, microfluidics as a research tool is unparalleled in terms of its biocompatibility, robustness, efficient reagent consumption, and controlled fluidic, surface, and structure environments. The controlled environments are essential in assessing the complex behavior of cells in response to microenvironmental cues.

A ratiometric fluorescent core-shell nanoprobe for sensing and imaging of zinc(II) in living cell and zebrafish.

A zinc(II)-responsive ratiometric fluorescent core-shell nanoprobe (referred to as QPNPs) is described. It consist of an optimized combination of an internal reference dye (TBAP) encapsulated in the core, and a Zn(II)-specific indicator dye (PEIQ) in the shell. The nanoprobe was synthesized via single-step graft copolymerization induced by tert-butyl hydroperoxide at 80 °C.

A fast and low-cost microfabrication approach for six types of thermoplastic substrates with reduced feature size and minimized bulges using sacrificial layer assisted laser engraving.

Since polydimethylsiloxane (PDMS) is notorious for its severe sorption to biological compounds and even nanoparticles, thermoplastics become a promising substrate for microdevices. Although CO laser engraving is an efficient method for thermoplastic device fabrication, it accompanies with poor bonding issues due to severe bulging and large feature size determined by the diameter of laser beam. In this study, a low-cost microfabrication method is proposed by reversibly sealing a 1 mm thick polymethylmethacrylate (PMMA) over an engraving substrate to reduce channel feature size and minimize bulges of laser engraved channels.

Controllable synthesis of functional nanoparticles by microfluidic platforms for biomedical applications - a review.

Nanoparticles have drawn significant attention in biomedicine due to their unique optical, thermal, magnetic and electrical properties which are highly related to their size and morphologies. Recently, microfluidic systems have shown promising potential to modulate critical stages in nanosynthesis, such as nucleation, growth and reaction conditions so that the size, size distribution, morphology, and reproducibility of nanoparticles are optimized in a high throughput manner. In this review, we put an emphasis on a decade of developments of microfluidic systems for engineering nanoparticles in various applications including imaging, biosensing, drug delivery, and theranostic applications.

Deposition of gadolinium onto the shell structure of micelles for integrated magnetic resonance imaging and robust drug delivery systems.

Selective deposition of Gd(iii) ions onto the shell structure of complex micelles was achieved to yield Gd decorated hybrid micelles for integrated magnetic resonance imaging and drug delivery. The complex micelles were engineered by the hydrophilic-hydrophobic self-assembly of two kinds of amphiphilic polymers, pluronic F127 and a peptide-amphiphile (PA), via a facile, environmentally benign strategy. These core-shell complex micelles provide a robust multifunctional platform for theranostic applications.

Grafting polyethylenimine with quinoline derivatives for targeted imaging of intracellular Zn(2+) and logic gate operations.

In this study, a highly sensitive and selective fluorescent Zn(2+) probe which exhibited excellent biocompatibility, water solubility, and cell-membrane permeability, was facilely synthesized in a single step by grafting polyethyleneimine (PEI) with quinoline derivatives. The primary amino groups in the branched PEI can increase water solubility and cell permeability of the probe PEIQ, while quinoline derivatives can specifically recognize Zn(2+) and reduce the potential cytotoxicity of PEI. Basing on fluorescence off-on mechanism, PEIQ demonstrated excellent sensing capability towards Zn(2+) in absolute aqueous solution, where a high sensitivity with a detection limit as low as 38.

Design of Multiple Logic Gates Based on Chemically Triggered Fluorescence Switching of Functionalized Polyethylenimine.

In this study, two new functionalized polyethylenimine (PEI), PEIR and PEIQ, have been synthesized by covalently conjugating rhodamine 6G (R6G) or 8-chloroacetyl-aminoquinoline (CAAQ) and have been investigated for their sensing capabilities toward metal ions and anions basing on fluorescence on-off and off-on mechanisms. When triggered by protons, metal ions, or anions, functionalized PEIs can behave as a fluorescence switch, leading to a multiaddressable system. Inspired by these results, functionalized PEI-based logic systems capable of performing elementary logic operations (YES, NOT, NOR, and INHIBIT) and integrative logic operations (OR + INHIBIT) have been constructed by observing the change in the fluorescence with varying the chemical inputs such as protons, metal ions, and anions.

Synthesis, characterization and biomedical application of multifunctional luminomagnetic core-shell nanoparticles.

It has been well-established that nanomaterials provide a robust framework into which two or more functional moieties can be integrated to offer multifunctional and synergetic applications. We report here the facile synthesis and systematical investigation of the luminomagnetic core-shell nanoparticles (NPs) with the magnetic Fe3O4 core coated with a silica shell incorporating fluorescent [Ru(bpy)3](2+). The luminomagnetic NPs were monodisperse and spherical in shape with a diameter of 60±10 nm.

A microfluidic linear node array for the study of protein-ligand interactions.

We have developed a microfluidic device for the continuous separation of small molecules from a protein mixture and demonstrated its practical use in the study of protein-ligand binding, a crucial aspect in drug discovery. Our results demonstrated dose-dependent binding between bovine serum albumin (BSA) and its small-molecule site marker, Eosin Y (EY), and found that the binding reached a plateau when the BSA : EY ratio was above 1, which agreed with the eosin binding capacity of BSA reported in literature. By streamline control using a combination of two fundamental building blocks (R and L nodes) with a microdevice operated at a high flow rate (up to 1300 μL h(-1)), a solution barrier was created to "filter" off protein/protein-ligand complexes such that the small unbound molecules were isolated and quantified easily.

Discovery of a benzofuran derivative (MBPTA) as a novel ROCK inhibitor that protects against MPP⁺-induced oxidative stress and cell death in SH-SY5Y cells.

Parkinson disease (PD) is a neurodegenerative disease with multifactorial etiopathogenesis. The discovery of drug candidates that act on new targets of PD is required to address the varied pathological aspects and modify the disease process. In this study, a small compound, 2-(5-methyl-1-benzofuran-3-yl)-N-(5-propylsulfanyl-1,3,4-thiadiazol-2-yl) acetamide (MBPTA) was identified as a novel Rho-associated protein kinase inhibitor with significant protective effects against 1-methyl-4-phenylpyridinium ion (MPP(+))-induced damage in SH-SY5Y neuroblastoma cells.

A novel dual-emission ratiometric fluorescent nanoprobe for sensing and intracellular imaging of Zn2+.

The integration of unique characteristics of nanomaterials with highly specific recognition elements, such as biomolecules and organic molecules, are the foundation of many novel nanoprobes for bio/chemical sensing and imaging. In the present report, branched polyethylenimine (PEI) was grafted with 8-chloroacetyl-aminoquinoline to synthesize a water-soluble and biocompatible quinoline-based Zn(2+) probe PEIQ. Then the PEIQ was covalently conjugated to [Ru(bpy)3](2+)-encapsulated SiNPs to obtain the ratiometric fluorescence nanoprobe which exhibits a strong fluorescence emission at 600 nm and a negligible fluorescence emission at 500 nm in the absence of Zn(2+) upon a single wavelength excitation.

Single layer linear array of microbeads for multiplexed analysis of DNA and proteins.

In this study, a microfluidic platform was developed to generate single layer, linear array of microbeads for multiplexed high-throughput analysis of biomolecules. The microfluidic device is comprised of eight microbead-trapping units, where microbeads were immobilized in a linear array format by the exertion of a negative pressure in the control channel connected to each sieving microstructure. Multiplexed assays were achieved by using a mixture of different spectrally-encoded microbeads functionalized with specific probes, followed by on-chip reaction and detection.

Microfluidics study of intracellular calcium response to mechanical stimulation on single suspension cells.

A microfluidic microdevice was developed to exert mechanical stimulation on an individual suspension cell for mechanosensation research. In this microfluidic chip, an individual cell was isolated from a population of cells, and trapped in a microchannel with a compressive component made of a deflectable membrane. The mechanosensation of HL60 cells (leukemic cells) was studied using this chip, and the results showed that mechanical stimulations could trigger extracellular calcium to flow into HL60 cells through ion channels on cell membranes.

Screen printing of solder resist as master substrates for fabrication of multi-level microfluidic channels and flask-shaped microstructures for cell-based applications.

Although silicon technology can be adopted for the fabrication of microfluidic devices with high precision, the capital and operating costs for such technology is often prohibitively expensive. In recent years, many alternative methods have been advocated to reduce the cost of microfabrication but often with reduced qualities in many important features, such as channel resolution, surface smoothness and aspect ratio. In this study, we have developed a microfabrication method that retains high channel quality and aspect ratio by exploring a rarely used solder resist material in combination with screen printing technique to generate masters where PDMS-based microfluidic devices could be fabricated by replica molding from the masters.

Multienzyme-nanoparticles amplification for sensitive virus genotyping in microfluidic microbeads array using Au nanoparticle probes and quantum dots as labels.

A novel microfluidic device with microbeads array was developed and sensitive genotyping of human papillomavirus was demonstrated using a multiple-enzyme labeled oligonucleotide-Au nanoparticle bioconjugate as the detection tool. This method utilizes microbeads as sensing platform that was functionalized with the capture probes and modified electron rich proteins, and uses the horseradish peroxidase (HRP)-functionalized gold nanoparticles as label with a secondary DNA probe. The functionalized microbeads were independently introduced into the arrayed chambers using the loading chip slab.

Integrated sieving microstructures on microchannels for biological cell trapping and droplet formation.

We have developed a single step microfabrication method to prepare constriction microstructures on a PCB master by controlling the etching time of two microchannels separated by a finite distance that is easily attainable using imagesetters widely available in the printing industry. PDMS replica of the constriction structures present sieving microstructures (microsieves) that could be used for size-dependent trapping of microspheres, biological cells and the formation of water-in-oil droplets.

Whole gene amplification and protein separation from a few cells.

Despite the growing interest to explore untapped microbial gene and protein diversity, no single platform has been able to acquire both gene and protein information from just a few cells. We present a microfluidic system that simultaneously performs on-chip capillary electrophoresis for protein analysis and whole genome amplification (WGA), and we demonstrate this by doing both for the same cohort of cyanobacterial cells. This technology opens avenues for studying protein profiles of precious environmental microbial samples and simultaneously accessing genomic information based on WGA.

Particle sorting using a porous membrane in a microfluidic device.

Porous membranes have been fabricated based on the development of the perforated membrane mold [Y. Luo and R. N.

Real-time monitoring of suspension cell-cell communication using an integrated microfluidics.

For the first time, we have developed a microfluidic device for on-chip monitoring of suspension cell-cell communication from stimulated to recipient HL-60 cells. A deformable PDMS membrane was developed as a compressive component to perform cell entrapment and exert different modes of mechanical stimulation. The number of cells trapped by this component could be modulated by flushing excessive cells towards the device outlet.

Patterned growth of vertically aligned silicon nanowire arrays for label-free DNA detection using surface-enhanced Raman spectroscopy.

Patterning is of paramount importance in many areas of modern science and technology. As a good candidate for novel nanoscale optoelectronics and miniaturized molecule sensors, vertically aligned silicon nanowire (SiNW) with controllable location and orientation is highly desirable. In this study, we developed an effective procedure for the fabrication of vertically aligned SiNW arrays with micro-sized features by using single-step photolithography and silver nanoparticle-induced chemical etching at room temperature.

A microfluidic device with microbead array for sensitive virus detection and genotyping using quantum dots as fluorescence labels.

In this study, a novel microfluidic device with microbead array was developed and sensitive genotyping of HBV was demonstrated using quantum dot as labels. This device was assembled by using two PDMS slabs featured with different microstructures and channel depths for the construction of a functional region comprising a chamber array and a single sampling microchannel. Since the chamber array and its sampling channel are of different channel depths and are bonded face-to-face, weir structures are generated to confine the microbeads which could be addressed using the microfluidic channel.

Microfluidic formation of single cell array for parallel analysis of Ca2+ release-activated Ca2+ (CRAC) channel activation and inhibition.

High-throughput single cell analysis is required for understanding and predicting the complex stochastic responses of individual cells in changing environments. We have designed a microfluidic device consisting of parallel, independent channels with cell-docking structures for the formation of an array of individual cells. The microfluidic cell array was used to quantify single cell responses and the distribution of response patterns of calcium channels among a population of individual cells.

3-D streamline steering by nodes arrayed in an entangled microfluidic network.

A vital part of microfluidic designs is to impose control over fluid streamlines by microscale structures. In this paper, we describe a method to control streamline steering through different microfluidic entangled networks. These networks were constructed by stacking two distinguishable layers of microchannels face-to-face.