Interaction between tumor and endothelial cells could affect tumor growth and progression and induce drug resistance during cancer therapy. Investigation of tumor–endothelial cell interaction involves cell coculture, protein detection, and analysis of drug metabolites, which are complicated and time-consuming. In this work, we present an integrated microfluidic device with three individual components (cell coculture component, protein detection component, and pretreatment component for drug metabolites) to probe the interaction between tumor and endothelial cells. Cocultured cervical carcinoma cells (CaSki cells) and human umbilical vein endothelial cells (HUVECs) show higher resistance to chemotherapeutic agents than single-cultured cells, indicated by higher cell viability, increased expression of angiogenic proteins, and elevated level of paclitaxel metabolites under coculture conditions. This integrated microfluidic platform with multiple functions facilitates understanding of the interaction between tumor and endothelial cells, and it may become a promising tool for drug screening within an engineered tumor microenvironment.

In response to environmental variations, living cells need to arrange the conformational changes of macromolecules to achieve the specific biofunctions. Inspired by natural molecular machines, artificial macromolecular assemblies with controllable nanostructures and environmentally responsive functions can be designed. By assembling macromolecular nanostructures with noble metal nanoparticles, environmental information could be significantly amplified and modulated. However, manufacturing dynamic plasmonic nanostructures that are efficiently responsive to different stimuli is still a challenging task. Here we demonstrate a stimulus-responsive plasmonic nanosystem based on DNA origami-organized gold nanorods (GNRs). L-shaped GNR dimers were assembled on rhombus-shaped DNA origami templates. The geometry and chiral signals of the GNR nanoarchitectures respond to multiple stimuli, including glutathione reduction, restriction enzyme action, pH change, or photoirradiation. While the glutathione reduction or restriction enzyme caused irreversible changes in the plasmonic circular dichroism (CD) signals, both pH and light irradiation triggered reversible changes in the plasmonic CD. Our system transduces external stimuli into conformational changes and circular dichroism responses in near-infrared (NIR) wavelengths. By this approach, programmable optical reporters for essential biological signals can be fabricated.Keywords: DNA origami; gold nanorod; plasmonic chiral nanostructure; self-assembly; Stimulus-responsive;

We report an ultrasensitive, quantitative, and rapid bioluminescent immunosensor (ABS) for point-of-care testing (POCT) of the disease biomarker in clinical samples using double enzymes including alkaline phosphatase (ALP) and luciferase. In the presence of the biomarker, the ALP attached on the surface of immuno-nanocomplex dephosphorylates adenine triphosphate (ATP), subsequently inhibiting the ATP–luciferin–luciferase bioluminescent reaction. The highly sensitive response of ATP (picomolar level) allows for ultrasensitive detection of biomarker via the effective change of the bioluminescence intensity through ALP- and luciferase-catalyzed reactions, which can be quantitatively determined by a portable ATP detector. This ABS fulfills the criteria for POCT that performs sensitive (femtomolar level of biomarkers) and quantitative measurement quickly (less than 1 h) with minimal equipment (portable detector).

Exosomes, molecular cargos secreted by almost all mammalian cells, are considered as promising biomarkers to identify many diseases including cancers. However, the small size of exosomes (30–200 nm) poses serious challenges in their isolation from complex media containing a variety of extracellular vesicles (EVs) of different sizes, especially in small sample volumes. Here we present a viscoelasticity-based microfluidic system to directly separate exosomes from cell culture media or serum in a continuous, size-dependent, and label-free manner. Using a small amount of biocompatible polymer as the additive in the media to control the viscoelastic forces exerted on EVs, we are able to achieve a high separation purity (>90%) and recovery (>80%) of exosomes. The proposed technique may serve as a versatile platform to facilitate exosome analyses in diverse biochemical applications.Keywords: exosomes; microfluidics; microvesicles; separation; viscoelasticity;

•The SA-B-HRP nanocomplex is an effective signal amplification system in MIS.•MIS has been developed for detection of PCT and IL-6 simultaneously.•The LOD for PCT and IL-6 by MIS are 48.9 pg mL−1 and 1.0 pg mL−1, respectively.•MIS has successfully detected PCT and IL-6 simultaneously in serum samples.Simultaneous, sensitive and quantitative detection of biomarkers in infectious disease is crucial for guiding antimicrobial treatment and predicting prognosis. This work reported an ultrasensitive and quantitative microfluidic immunoassay combined with the streptavidin-biotin-peroxidase (SA-B-HRP) nanocomplex-signal amplification system (MIS) to detect two inflammatory biomarkers, procalcitonin (PCT, for discriminating bacterial infections from nonbacterial infections) and interleukin-6 (IL-6, for monitoring the kinetics of infectious disease) simultaneously. The amplification system was based on the one step self-assembly of SA and B-HRP to form the SA-B-HRP nanocomplex, which effectively amplified the chemiluminescent signals. The linear ranges for PCT and IL-6 detections by MIS were 250–1.28 × 105 pg mL−1 and 5–1280 pg mL−1, and the limit of detection (LOD) were 48.9 pg mL−1 and 1.0 pg mL−1, respectively, both of which were significantly improved compared with microfluidic immunoassays without amplification system (MI). More importantly, PCT and IL-6 in human serum could be simultaneously detected in the same run by MIS, which could greatly improve the detection efficiency and reduce the cost. Given the advantages of high sensitivity, multiplex and quantitative detection, MIS could be potentially applied for detection of biomarkers at low concentration in clinical diagnosis.Download high-res image (267KB)Download full-size image

Carbon deposition is an undesired side product, significantly inhibiting chemical reactions as well as leading to performance degradation. To efficiently prevent carbon deposition, the underlying mechanism needs to be elucidated. In this work, we have employed Raman spectroscopy to characterize the formed carbon deposits under different conditions inside a high temperature furnace heating system with a built-in U-shape quartz tube. The formation of graphite/amorphous carbon deposition was related to the temperature-dependent diffusion rate of carbon atoms, as well as the surface state of stainless steel. These investigations would help reduce unnecessary carbon deposition not only in ethylene but also in other industrial productions such as fuel cells.

The microfluidic passive control of microparticles largely relies on the hydrodynamic effects of the carrier media such as Newtonian fluids and viscoelastic fluids. Yet the viscoelastic/Newtonian interfacial effect has been scarcely investigated, especially for high-resolution particle separation. Here we report a microfluidic co-flow of Newtonian (water or PBS) and viscoelastic fluids (PEO) for the size-dependent separation of microparticles. The co-flow condition generates a stable viscoelastic/Newtonian interface, giving rise to the wall-directed elastic lift forces that compete with the center-directed lift forces, and efficiently hinders the migration of microparticles from the Newtonian to the viscoelastic fluid in a size-dependent manner. An almost complete separation of a binary mixture of 1 μm and 2 μm polystyrene particles is achieved by the co-flow of water and a very dilute PEO solution (100 ppm), whereas the sole use of water or PEO could not lead to an efficient separation. This co-flow microfluidic system is also applied for the separation of Staphylococcus aureus (1 μm) from platelets (2–3 μm) with >90% efficiencies and purities.

Microfluidic platforms capable of automated, rapid, sensitive, and quantitative detection of biomarkers from patient samples could make a major impact on clinical or point-of-care (POC) diagnosis. In this work, we realize an automated diagnostic platform composed of two main components: (1) a disposable, self-contained, and integrated microfluidic chip and (2) a portable instrument that carries out completely automated operations. To demonstrate its potential for real-world application, we use injection molding for mass fabrication of the main components of disposable microfluidic chips. The assembled three-layered chip with on-chip mechanical valves for fluid control consists of (1) a top silicone fluidic layer with embedded zigzag microchannels, reagent reservoirs and a negative pressure port, (2) a middle tinfoil layer with patterned antibody/antigen stripes, and (3) a bottom silicone substrate layer with waste reservoirs. The versatility of the microfluidics-based system is demonstrated by implementation of a chemiluminescence immunoassay for quantitative detection of C-reactive protein (CRP) and testosterone in real clinical samples. This lab-on-a-chip platform with features of quantitation, portability and automation provides a promising strategy for POC diagnosis.

•Point-of-care testing of nucleic acids greatly improves health monitoring and prevents outbreak of infectious diseases.•Portable platforms without complicated equipment or laborious operations allow for POCT in resource-limited settings.•Recent advances in diagnostics of nucleic acids in POC formats are reviewed.•The microfluidics-based techniques, including on-chip sample preparation, amplification, and signal read-out, are discussed.Nucleic acid detection offers critical information in diagnosing pathogen infection and monitoring disease treatment. Point-of-care testing (POCT), with ideal characteristics such as rapidness, user-friendly, sensitivity, specificity, and robustness, has drawn wide attention, especially in resource-poor settings where lack the healthcare infrastructure. Accompanied by the development of microfluidic technologies and new amplification methods, POCT of nucleic acids greatly improves health monitoring and prevents outbreak of infectious diseases. This review summarizes recent advances in diagnostics of nucleic acids in POC formats, and discusses challenges associated with POCT of nucleic acids.

The controlled synthesis of functional nanoparticles with tunable structures and properties has been extensively investigated for cancer treatment and diagnosis. Among a variety of methods for fabrication of nanoparticles, microfluidics-based synthesis enables enhanced mixing and precise fluidic modulation inside microchannels, thus allowing for the flow-mediated production of nanoparticles in a controllable manner. This review focuses on recent advances of using microfluidic devices for the synthesis of drug-loaded nanoparticles with specific characteristics (such as size, composite, surface modification, structure and rigidity) for enhanced cancer treatment and diagnosis as well as to investigate the bio-nanoparticle interaction. The discussion on microfluidics-based synthesis may shed light on the rational design of functional nanoparticles for cancer-related pharmaceutical applications.

We report a nonspecific organelle-targeting strategy through one-step microfluidic fabrication and screening of a library of surface charge- and lipid components/ratios-varied lipid shell–polymer core nanoparticles. Different from the common strategy relying on the use of organelle-targeted moieties conjugated onto the surface of nanoparticles, here, we program the distribution of hybrid nanoparticles in lysosomes or mitochondria by tuning the lipid components/ratios in shell. Hybrid nanoparticles with 60% 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 20% 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) can intracellularly target mitochondria in both in vitro and in vivo models. While replacing DOPE with the same amount of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), the nanoparticles do not show mitochondrial targeting, indicating an incremental effect of cationic and fusogenic lipids on lysosomal escape which is further studied by molecular dynamics simulations. This work unveils the lipid-regulated subcellular distribution of hybrid nanoparticles in which target moieties and complex synthetic steps are avoided.

We demonstrate a microfluidic-based indirect competitive chemiluminescence enzyme immunoassay (MIC) for multiple, sensitive, reliable and rapid detection of testosterone in human serum and urine samples. As MIC can detect biomarkers in a cost-effective and easy-to-operate manner, it may have great potential for clinical diagnosis and point-of-care testing (POCT).

One-step, quantitative and rapid detection of microRNA (miRNA) in tumor cells or tissues can provide critical information for clinical diagnosis and cancer treatment. In this work, we develop a magnetic relaxation switch sensing (MRS)-based miRNA sensor using magnetic microparticle (1 μm in diameter, MM1000)-DNA probe-magnetic nanoparticle (30 nm in diameter, MN30) conjugates (MM1000-DNA-MN30). In the presence of target miRNA, DSN enzyme selectively cleaves the DNA tether after miRNA/DNA hybridization to release MN30 and leaves the miRNA intact to lead to the declustering of more MN30 than before. In contrast to conventional MRS by measuring the change of transverse relaxation time (ΔT2) induced by the aggregation or dissociation of magnetic particles in the presence of target, we use the cleaved MN30 from conjugates as the direct readout of ΔT2, which is more sensitive and stable. This MRS-based assay allows for one-step detection of 5 fM of miR-21 in urine samples, quantification of miR-21 from 100 cancer cells, and differentiation of the expression of miR-21 in tumor and surrounding tissues. The merits of this assay, rapidity, ability for quantitation, high sensitivity, and one-step operation, ensure a promising future in diagnostic technology.Keywords: detection; magnetic nanoparticles; magnetic relaxation switch; miRNA; tumor

Nanocrystalline cellulose (NCC) is a kind of natural biopolymers with merits of large surface area, high specific strength and unique optical properties. This report shows that NCC can serve as the substrate, allowing glucose to reduce Tollen’s reagent to produce silver nanoparticles (AgNPs) at room temperature. The generation of AgNPs is affected by the factors such as the concentrations of silver ions, NCC and glucose, as well as the different reaction temperatures. The AgNPs with NCC are applied for the development of a visual, quantitative, nonenzymatic and high-sensitive assay for glucose detection in serum. This assay is also used for monitoring the concentration change of glucose in medium during cell culture. For the antibacterial activity, the minimal inhibitory concentration (MIC) of the generated AgNPs with NCC is much lower than that of commercial AgNPs, attributed to the good dispersion of AgNPs with the presence of NCC. As NCC exhibits unique advantages including green, stable, inexpensive, and abundant, the NCC-based generation of AgNPs may find promising applications in clinical diagnosis, environmental monitoring, and the control of bacteria.

The doping of biocompatible nanomaterials into ultrahigh molecular weight polyethylene (UHMWPE) to improve the biocompatibility and reduce the wear debris is of great significance to prolonging implantation time of UHMWPE as the bearing material for artificial joints. This study shows that UHMWPE can form a composite with nanocrystalline cellulose (NCC, a hydrophilic nanosized material with a high aspect ratio) by ball-milling and hot-pressing. Compared to pure UHMWPE, the NCC/UHMWPE composite exhibits improved tribological characteristics with reduced generation of wear debris. The underlying mechanism is related to the weak binding between hydrophilic NCC and hydrophobic UHMWPE. The hydrophilic, rigid NCC particles tend to detach from the UHMWPE surface during friction, which could move with the rubbing surface, serve as a thin lubricant layer, and protect the UHMWPE substrate from abrasion. The biological safety of the NCC/UHMWPE composite, as tested by MC3T3-E1 preosteoblast cells and macrophage RAW264.7 cells, is high, with significantly lower inflammatory responses/cytotoxicity than pure UHMWPE. The NCC/UHMWPE composite therefore could be a promising alternative to the current UHMWPE for bearing applications.Keywords: artificial joint; debris; friction; nanocrystalline cellulose; ultrahigh molecular weight polyethene;

Viscoelastic microfluidics becomes an efficient and label-free hydrodynamic technology to enrich and separate micrometer-scale particles, including blood cells, circulating tumor cells, and bacteria. However, the manipulation of nanoscale particles by viscoelastic microfluidics remains a major challenge, because the viscoelastic force acting on the smaller particle decreases dramatically. In contrast to the commonly used polymer solutions of high molecular weight, herein we utilize the aqueous solutions of poly(ethylene oxide) (PEO) of low molecular weight with minimized shear thinning but sufficient elastic force for high-quality focusing and separation of various nanoparticles. The focusing efficiencies of 100 nm polystyrene (PS) nanoparticles and λ-DNA molecules are 84% and 85%, respectively, in a double spiral microchannel, without the aid of sheath flows. Furthermore, we demonstrate the size-based viscoelastic separation of two sets of binary mixtures—100/2000 nm PS particles and λ-DNA molecules/blood platelets—all achieving separation efficiencies of >95% in the same device. Our proposal technique would be a promising approach for enrichment/separation of the nanoparticles encountered in applications of analytical chemistry and nanotechnology.

•MTNT enables high-throughput detection of both DNA and RNA from crude samples.•MTNT has an excellent sensitivity and specificity, with the LOD of 2 copies.•MTNT can detect mRNA from as few as 2 cancer cells without complicated procedures.We develop a micro-pipette tip-based nucleic acid test (MTNT) for high-throughput sample-to-answer detection of both DNA and RNA from crude samples including cells, bacteria, and solid plants, without the need of sample pretreatment and complex operation. MTNT consists of micro-pipette tips and embedded solid phase nucleic acid extraction membranes, and fully integrates the functions of nucleic acid extraction from crude samples, loop-mediated isothermal amplification (LAMP) of nucleic acids, and visual readout of assays. The total assaying time for DNA or RNA from a variety of crude samples ranges from 90 to 160 min. The limit of detection (LOD) of MTNT is 2 copies of plasmids containing the target nucleic acid fragments of Ebola virus, and 8 CFU of Escherichia coli carrying Ebola virus-derived plasmids. MTNT can also detect CK-19 mRNA from as few as 2 cancer cells without complicated procedures such as RNA extraction and purification. We further demonstrate MTNT in a high-throughput format using an eight-channel pipette and a homemade mini-heater, with a maximum throughput of 40 samples. Compared with other point-of-care (POC) nucleic acid tests (NAT), MTNT could assay both DNA and RNA directly from liquid (cells/bacteria/blood) or solid (plant) samples in a straightforward, sensitive, high-throughput, and containment-free manner, suggesting a considerable promise for low-cost and POC NAT in remote areas.

The Ligament Advanced Reinforcement System (LARS) has been considered as a promising graft for ligament reconstruction. To improve its biocompatibility and effectiveness on new bone formation, we modified the surface of a polyethylene terephthalate (PET) ligament with nanoscale silica using atom transfer radical polymerization (ATRP) and silica polymerization. The modified ligament is tested by both in vitro and in vivo experiments. Human osteoblast testing in vitro exhibits an ∼21% higher value in cell viability for silica-modified grafts compared with original grafts. Animal testing in vivo shows that there is new formed bone in the case of a nanoscale silica-coated ligament. These results demonstrate that our approach for nanoscale silica surface modification on LARS could be potentially applied for ligament reconstruction.

Inertial microfluidics has emerged as an important tool for manipulating particles and cells. For a better design of inertial microfluidic devices, we conduct 3D direct numerical simulations (DNS) and experiments to determine the complicated dependence of focusing behaviour on the particle size, channel aspect ratio, and channel Reynolds number. We find that the well-known focusing of the particles at the two centers of the long channel walls occurs at a relatively low Reynolds number, whereas additional stable equilibrium positions emerge close to the short walls with increasing Reynolds number. Based on the numerically calculated trajectories of particles, we propose a two-stage particle migration which is consistent with experimental observations. We further present a general criterion to secure good focusing of particles for high flow rates. This work thus provides physical insight into the multiplex focusing of particles in rectangular microchannels with different geometries and Reynolds numbers, and paves the way for efficiently designing inertial microfluidic devices.

This work develops a high-throughput, high-efficiency and straightforward microfluidic blotting method for analyzing proteins and nucleic acids. Sample solutions containing antibodies (for protein detection) or hybridization probes (for nucleic acid detection) are introduced into the parallel, serpentine microchannels to specifically recognize the immobilized targets on the substrate, achieving the identification of multiple targets in multiple samples simultaneously. The loading control, molecular weight markers, and antigen/antibody titration are designed and integrated into the microfluidic chip, thus allowing for the quantification of proteins and nucleic acids. Importantly, we could easily distinguish the adjacent blotting bands inside parallel microchannels, which may be difficult to achieve in conventional blotting. The small dimensions of microfluidic channels also help to reduce the amount of probing molecules and to accelerate the biochemical reaction. Our microfluidic blotting could bypass the steps of blocking and washing, further reducing the operation time and complexity.

Multiplexed assay of analytes is of great importance for clinical diagnostics and other analytical applications. Barcode-based bioassays with the ability to encode and decode may realize this goal in a straightforward and consistent manner. We present here a microfluidic barcoded chip containing several sets of microchannels with different widths, imitating the commonly used barcode. A single barcoded microchip can carry out tens of individual protein/nucleic acid assays (encode) and immediately yield all assay results by a portable barcode reader or a smartphone (decode). The applicability of a barcoded microchip is demonstrated by human immunodeficiency virus (HIV) immunoassays for simultaneous detection of three targets (anti-gp41 antibody, anti-gp120 antibody, and anti-gp36 antibody) from six human serum samples. We can also determine seven pathogen-specific oligonucleotides by a single chip containing both positive and negative controls.

We develop an inertial-based microfluidic cell sorter combined with an integrated membrane filter, allowing for size-based, label-free, and high-efficiency separation and enrichment of circulating tumor cells (CTCs) in whole blood. The cell sorter is composed of a double spiral microchannel that hydrodynamically focuses and separates large CTCs from small blood cells. The focused CTCs with the equilibrium position around the midline of microchannel are further captured and enriched by a membrane filter (pore size of 8 μm) attached at the middle outlet. This integrated microfluidic device can process 1 mL of whole blood containing spiked tumor cells (A549, human lung adenocarcinoma epithelial cell line) within 15 min, with the capture efficiency of 74.4% at the concentration as low as tens of A549 cells per mL of whole blood. This microfluidic cell sorter is further adopted for isolation of CTCs from peripheral blood samples of patients with metastatic lung cancer. The immunostaining and CK-19 mRNA detection are applied for identification of captured CTCs, showing that our method can detect 90% of metastatic lung cancer patients before therapy, whereas the commercially used system can only detect 40% of the same patients. We also use the expression of CK-19 mRNA from captured CTCs as an indicator for monitoring the therapeutic efficiency, which correlates well with X-ray computed tomography (CT) assessment of the disease.

We report a sensing methodology that combines magnetic separation (MS) and magnetic relaxation switching (MS-MRS) for one-step detection of bacteria and viruses with high sensitivity and reproducibility. We first employ a magnetic field of 0.01 T to separate the magnetic beads of large size (250 nm in diameter) from those of small size (30 nm in diameter) and use the transverse relaxation time (T2) of the water molecules around the 30 nm magnetic beads (MB30) as the signal readout of the immunoassay. An MS-MRS sensor integrates target enrichment, extraction, and detection into one step, and the entire immunoassay can be completed within 30 min. Compared with a traditional MRS sensor, an MS-MRS sensor shows enhanced sensitivity, better reproducibility, and convenient operation, thus providing a promising platform for point-of-care testing.Keywords: homogeneous immunosensor; magnetic bead; magnetic relaxation switch; magnetic separation; one-step detection;

The functionalized lipid shell of hybrid nanoparticles plays an important role for improving their biocompatibility and in vivo stability. Yet few efforts have been made to critically examine the shell structure of nanoparticles and its effect on cell–particle interaction. Here we develop a microfluidic chip allowing for the synthesis of structurally well-defined lipid-polymer nanoparticles of the same sizes, but covered with either lipid-monolayer-shell (MPs, monolayer nanoparticles) or lipid-bilayer-shell (BPs, bilayer nanoparticles). Atomic force microscope and atomistic simulations reveal that MPs have a lower flexibility than BPs, resulting in a more efficient cellular uptake and thus anticancer effect than BPs do. This flexibility-regulated cell–particle interaction may have important implications for designing drug nanocarriers.Keywords: drug deliver; interfaces; lipids; microfluidics; nanostructures;

Electrospinning technology underwent rapid development in recent years, which can be used for fabricating electrospun fibers with different morphologies and multidimensional structures. These fibers are widely applied in medical diagnosis, tissue engineering, replica molding and other applications. Here we review the recent advances in the electrospinning technology, especially technical progress in fabricating electrospun fibers and assemblies with multidimensional structures, and the biomedical applications of these fibers.

In this paper, we present a simple but efficient biomimetic method to encapsulate laccase on mesoporous silica-modified electrospun (ES) ultrafine fibers. Because of the mild immobilization conditions (room temperature, aqueous condition), the encapsulated laccase retained a high activity of 94%. Because of the protection from the silica layer, the laccase worked efficiently at 60 °C and retained a long-term activity in the presence of proteinase K. After recycling for 10 times the laccase still preserved 96% of its original reactivity. More remarkably, the immobilized laccase on fibers could completely recover its activity after thermal denature, while the free laccase permanently lost the activity. We also demonstrated that the laccase on silica-coated fibers exhibited an enhanced decolorization capability of Brilliant Blue KN-R (BBKN-R) as compared to the free laccase, showing its great potential for industrial applications.

This report describes a straightforward but robust tubing method for connecting polydimethylsiloxane (PDMS) microfluidic devices to external equipment. The interconnection is irreversible and can sustain a pressure of up to 4.5 MPa that is characterized experimentally and theoretically. To demonstrate applications of this high-pressure tubing technique, we fabricate a semicircular microfluidic channel to implement a high-throughput, size-controlled synthesis of poly(lactic-co-glycolic acid) (PLGA) nanoparticles ranging from 55 to 135 nm in diameter. This microfluidic device allows for a total flow rate of 410 mL h−1, resulting in enhanced convective mixing which can be utilized to precipitate small size nanoparticles with a good dispersion. We expect that this tubing technique would be widely used in microfluidic chips for nanoparticle synthesis, cell manipulation, and potentially nanofluidic applications.

This report demonstrates a straightforward, robust, multiplexed and point-of-care microcapillary-based loop-mediated isothermal amplification (cLAMP) for assaying nucleic acids. This assay integrates capillaries (glass or plastic) to introduce and house sample/reagents, segments of water droplets to prevent contamination, pocket warmers to provide heat, and a hand-held flashlight for a visual readout of the fluorescent signal. The cLAMP system allows the simultaneous detection of two RNA targets of human immunodeficiency virus (HIV) from multiple plasma samples, and achieves a high sensitivity of two copies of standard plasmid. As few nucleic acid detection methods can be wholly independent of external power supply and equipment, our cLAMP holds great promise for point-of-care applications in resource-poor settings.

This work develops an integrated microcapillary-based loop-mediated isothermal amplification (icLAMP) containing preloaded reagents and DNA extraction card, allowing for sample-to-answer screening of single nucleotide polymorphisms (SNPs) typing of the CYP2C19 gene from untreated blood samples with minimal user operation. With all reagents and the DNA extraction card preloaded inside the capillary, this icLAMP system can achieve on-site pretreatment, extraction, amplification, and detection of nucleic acids within 150 min, without the requirement for advanced instruments. As icLAMP technology carries many advantages such as disposability, easy operation, low cost, and reduced cross contamination and biohazard risks, we expect this system to have a great impact on point-of-care (POC) nucleic acid detection.

In this work, we fabricated polymeric fibrous scaffolds for bone tissue engineering using primary human osteoblasts (HOB) as the model cell. By employing one simple approach, electrospinning, we produced poly(lactic-co-glycolic acid) (PLGA) scaffolds with different topographies including microspheres, beaded fibers, and uniform fibers, as well as the PLGA/nanohydroxyapatite (nano-HA) composite scaffold. The bone-bonding ability of electrospun scaffolds was investigated by using simulated body fluid (SBF) solution, and the nano-HA in PLGA/nano-HA composite scaffold can significantly enhance the formation of the bonelike apatites. Furthermore, we carried out in vitro experiments to test the performance of electrospun scaffolds by utilizing both mouse preosteoblast cell line (MC 3T3 E1) and HOB. Results including cell viability, alkaline phosphatase (ALP) activity, and osteocalcin concentration demonstrated that the PLGA/nano-HA fibers can promote the proliferation of HOB efficiently, indicating that it is a promising scaffold for human bone repair.Keywords: biodegradable scaffold; electrospinning; human bone repair; hydroxyapatite; microstructure;

This work reports on a passive double spiral microfluidic device allowing rapid and label-free tumor cell separation and enrichment from diluted peripheral whole blood, by exploiting the size-dependent hydrodynamic forces. A numerical model is developed to simulate the Dean flow inside the curved geometry and to track the particle/cell trajectories, which is validated against the experimental observations and serves as a theoretical foundation for optimizing the operating conditions. Results from separating tumor cells (MCF-7 and Hela) spiked into whole blood indicate that 92.28% of blood cells and 96.77% of tumor cells are collected at the inner and the middle outlet, respectively, with 88.5% tumor recovery rate at a throughput of 3.33 × 107 cells min−1. We expect that this label-free microfluidic platform, driven by purely hydrodynamic forces, would have an impact on fundamental and clinical studies of circulating tumor cells.

Electrospinning technology underwent rapid development in recent years, which can be used for fabricating electrospun fibers with different morphologies and multidimensional structures. These fibers are widely applied in medical diagnosis, tissue engineering, replica molding and other applications. Here we review the recent advances in the electrospinning technology, especially technical progress in fabricating electrospun fibers and assemblies with multidimensional structures, and the biomedical applications of these fibers.