Microfluidic platforms integrated with nano-sensors for point-of-care bioanalysis.

Microfluidic technology provides a portable, cost-effective, and versatile tool for point-of-care (POC) bioanalysis because of its associated advantages such as fast analysis, low volumes of reagent consumption, and high portability. Along with microfluidics, the application of nanomaterials in biosensing has attracted lots of attention due to their unique physical and chemical properties for enhanced signal modulation such as signal amplification and signal transduction for POC bioanalysis. Hence, an enormous number of microfluidic devices integrated with nano-sensors have been developed for POC bioanalysis targeting low-resource settings. Herein, we review recent advances in POC bioanalysis on nano-sensor-based microfluidic platforms. We first briefly summarized the different types of cost-effective microfluidic platforms, followed by a concise introduction to nanomaterial-based biosensors. Then, we highlighted the application of microfluidic platforms integrated with nano-sensors for POC bioanalysis. Finally, we discussed the current limitations and perspective trends of the nano-sensor-based microfluidic platforms for POC bioanalysis.

Integration and Quantitative Visualization of 3,3',5,5'-Tetramethylbenzidine-Probed Enzyme-Linked Immunosorbent Assay-like Signals in a Photothermal Bar-Chart Microfluidic Chip for Multiplexed Immunosensing.

The photothermal effect shows significant promise for various biomedical applications but is rarely exploited for microfluidic lab-on-a-chip bioassays. Herein, a photothermal bar-chart microfluidic immunosensing chip, with the integration of the conventional 3,3',5,5'-tetramethylbenzidine (TMB)-probed enzyme-linked immunosorbent assay (ELISA)-like system, was developed based on exploiting the photothermal pumping technique for visual bar-chart microfluidic immunosensing. Both the sandwich ELISA-like system and the photothermal pumping protocol were integrated into a single photothermal bar-chart chip. On-chip immunocaptured iron oxide nanoparticles catalyzed the oxidation of the chromogenic substrate, TMB, to produce a sensitive photothermal and chromogenic dual-functional probe, oxidized TMB. As the result of heat generation and the subsequent production of elevating vapor pressure in the sealed microfluidic environment, the on-chip near-infrared laser-driven photothermal effect of the probe served as a dose-dependent pumping force to drive the multiplexed quantitative display of the immunosensing signals as visual dye bar charts. Prostate-specific antigen as a model analyte was tested at a limit of detection of 1.9 ng·mL-1, lower than the clinical diagnostic threshold of prostate cancer. This work presents a new perspective for microfluidic integration and multiplexed quantitative bar-chart visualization of the conventional TMB-probed ELISA signals possibly by means of an affordable handheld laser pointer in a lab-on-a-chip format.

Detector-Free Photothermal Bar-Chart Microfluidic Chips (PT-Chips) for Visual Quantitative Detection of Biomarkers.

The volumetric bar-chart microfluidic chips (V-Chips) driven by chemical reaction-generated gas provide a promising platform for point-of-care (POC) visual biomarker quantitation. However, multiple limitations are encountered in conventional V-Chips, such as costly and complex chip fabrication, complicated chip assembly, and imprecise controllability of gas production. Herein, we introduced nanomaterial-mediated photothermal effects to V-Chips, and for the first time developed a new type of V-Chip, photothermal bar-chart microfluidic chip (PT-Chip), for visual quantitative detection of biochemicals without any bulky and costly analytical instruments. Immunosensing signals were converted to visual readout signals via photothermal effects, the on-chip bar-chart movements, enabling quantitative biomarker detection on a low-cost polymer hybrid PT-Chip with on-chip scale rulers. Four different human serum samples containing a prostate-specific antigen (PSA) as a model analyte were detected simultaneously using the PT-Chip, with a limit of detection of 2.1 ng/mL, meeting clinical diagnostic requirements. Although no conventional signal detectors were used, it achieved comparable detection sensitivity to absorbance measurements with a microplate reader. The PT-Chip was further validated by testing human whole blood without the color interference problem, demonstrating the good analytical performance of our method even in complex matrices and thus the potential to fill the gap in current clinical diagnostics that is incapable of testing whole blood. This new PT-Chip driven by nanomaterial-mediated photothermal effects opens a new horizon of microfluidic platforms for instrument-free diagnostics at the point-of-care.

Photothermal Microfluidic Sensing Platform Using Near-Infrared Laser-Driven Multiplexed Dual-Mode Visual Quantitative Readout.

The application of different sensing principles in microfluidic devices opens up further possibilities for the development of point-of-care testing (POCT). Herein, the photothermal sensing principle is introduced in microfluidic paper-based analytical devices (µPADs) to develop a photothermal microfluidic sensing platform using near-infrared (NIR) laser-driven multiplexed dual-mode visual quantitative readout. Prussian blue (PB) as the analyte-associated photothermal agent was in situ synthesized in thermoresponsive poly(N-isopropylacrylamide) hydrogels to serve as the on-chip photothermal sensing element. The NIR laser-driven photothermal effect of PB triggered not only on-chip dose-dependent heat generation but also phase transition-induced dye release from the hydrogels, simultaneously enabling both thermal image- and distance-based dual-mode visual quantitative readout of the analyte concentration in a multiplexed manner. Both the on-chip temperature elevation value of the hydrogels and the traveling distance of released dye solutions were proportional to the concentration of PB. With the detection of silver ions in environmental water as a proof-of-concept study, the photothermal µPAD can detect silver ions at a concentration as low as 0.25 µM with high selectivity and satisfactory accuracy. The photothermal microfluidic sensing platform holds great potential for POCT with promising integratability and broad applicability, owing to the combination of synergistic advantages of the photothermal sensing principle, µPADs, and photothermally responsive hydrogels.

Exploration of Nanoparticle-Mediated Photothermal Effect of TMB-H2O2 Colorimetric System and Its Application in a Visual Quantitative Photothermal Immunoassay.

The exploration of new physical and chemical properties of materials and their innovative application in different fields are of great importance to advance analytical chemistry, material science, and other important fields. Herein, we, for the first time, discovered the photothermal effect of an iron oxide nanoparticles (NPs)-mediated TMB (3,3',5,5'-tetramethylbenzidine)-H2O2 colorimetric system, and applied it toward the development of a new NP-mediated photothermal immunoassay platform for visual quantitative biomolecule detection using a thermometer as the signal reader. Using a sandwich-type proof-of-concept immunoassay, we found that the charge transfer complex of the iron oxide NPs-mediated one-electron oxidation product of TMB (oxidized TMB) exhibited not only color changes, but also a strong near-infrared (NIR) laser-driven photothermal effect. Hence, oxidized TMB was explored as a new sensitive photothermal probe to convert the immunoassay signal into heat through the near-infrared laser-driven photothermal effect, enabling simple photothermal immunoassay using a thermometer. Based on the new iron oxide NPs-mediated TMB-H2O2 photothermal immunoassay platform, prostate-specific antigen (PSA) as a model biomarker can be detected at a concentration as low as 1.0 ng·mL-1 in normal human serum. The discovered photothermal effect of the colorimetric system and the developed new photothermal immunoassay platform open up a new horizon for affordable detection of disease biomarkers and have great potential for other important material and biomedical applications of interest.

Association between polymorphisms of glucocorticoid receptor genes and asthma: A meta-analysis.

Recent studies have evaluated the associations between polymorphisms of glucocorticoid receptor genes and asthma. However, the conclusions of these studies are conflicting. The objective of this meta-analysis was to clarify the association between all known polymorphisms of glucocorticoid receptor genetic loci and susceptibility to asthma, based on existing reports. We conducted a meta-analysis of the association between glucocorticoid receptor polymorphisms (NR3C1) and asthma risk. A systematical literature search was performed in PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), and Cochrane Library until January 15, 2018. The odds ratio (OR), 95% confidence interval (CI), and P value were calculated using Mantel-Haenszel statistics under the allele, homozygote, heterozygote, dominant, or recessive models. P values of less than 0.05 were considered to represent statistically significant associations between glucocorticoid receptor gene polymorphisms and asthma. All statistical analyses were done using the "meta" package (version 4.9-0) of R version 3.4.3 and RStudio version 1.0.44. A total of fourteen studies, reported via ten articles from online databases were included in our meta-analysis. For BclI (from eight studies), a significant association was detected in the allele model, homozygote model, and recessive model (C versus G: OR (95% CI) = 0.63 (0.40-0.97), CC versus GG: OR (95% CI) = 0.41(0.17-0.97), CC versus GC + GG: OR (95% CI) = 0.54(0.34-0.88)), but not in the heterozygote model or the dominant model. For ER22/23EK (from four studies), TthIII1 (from two studies), no significant association was found for any genetic model. After subgroup analyses by age, significant associations were observed for the allele model, homozygote model, dominant model and recessive model for BclI in adults. The ER22/23EK and TthIII1 polymorphisms were not found to be associated with susceptibility to ASTHMA; however, the BclI polymorphisms were significantly associated with ASTHMA in adults.

Cost-effective and sensitive colorimetric immunosensing using an iron oxide-to-Prussian blue nanoparticle conversion strategy.

The development of new sensitive, cost-effective and user-friendly colorimetric bioassays is in increasing demand to meet the requirement of modern clinical diagnostics and field detection. Herein, a novel iron oxide-to-Prussian blue (PB) nanoparticle (NP) conversion strategy was developed and applied to sensitive colorimetric immunosensing of cancer biomarkers. In a typical sandwich-type immunosensing system, the captured spherical antibody-conjugated iron oxide NPs were transformed into cubic PB NPs, which exhibited a highly visible blue color with high molar extinction coefficients. Hence, a new colorimetric immunosensing strategy was developed as a result of this low cost and simple transformation process. Without the aid of any complex nanoparticle stabilizing ligands and signal amplification processes, prostate-specific antigen as a model analyte can be detected at a concentration as low as 1.0 ng mL(-1) by the naked eye with good reliability for detection of real human serum samples. This is the first attempt to develop and apply the iron oxide-to-PB NP colorimetric conversion strategy for immunosensing, and shows great promise for the development of new sensitive, cost-effective and user-friendly colorimetric bioassays in various bioanalytical applications, especially in low-resource settings.

Biomarker detection for disease diagnosis using cost-effective microfluidic platforms.

Early and timely detection of disease biomarkers can prevent the spread of infectious diseases, and drastically decrease the death rate of people suffering from different diseases such as cancer and infectious diseases. Because conventional diagnostic methods have limited application in low-resource settings due to the use of bulky and expensive instrumentation, simple and low-cost point-of-care diagnostic devices for timely and early biomarker diagnosis is the need of the hour, especially in rural areas and developing nations. The microfluidics technology possesses remarkable features for simple, low-cost, and rapid disease diagnosis. There have been significant advances in the development of microfluidic platforms for biomarker detection of diseases. This article reviews recent advances in biomarker detection using cost-effective microfluidic devices for disease diagnosis, with the emphasis on infectious disease and cancer diagnosis in low-resource settings. This review first introduces different microfluidic platforms (e.g. polymer and paper-based microfluidics) used for disease diagnosis, with a brief description of their common fabrication techniques. Then, it highlights various detection strategies for disease biomarker detection using microfluidic platforms, including colorimetric, fluorescence, chemiluminescence, electrochemiluminescence (ECL), and electrochemical detection. Finally, it discusses the current limitations of microfluidic devices for disease biomarker detection and future prospects.

Magnetic Prussian blue nanoparticles for targeted photothermal therapy under magnetic resonance imaging guidance.

This paper reported a core-shell nanotheranostic agent by growing Prussian blue (PB) nanoshells of 3-6 nm around superparamagnetic Fe3O4 nanocores for targeted photothermal therapy of cancer under magnetic resonance imaging (MRI) guidance. Both in vitro and in vivo experiments proved that the Fe3O4@PB core-shell nanoparticles showed significant contrast enhancement for T2-weighted MRI with the relaxivity value of 58.9 mM(-1)·s(-1). Simultaneously, the composite nanoparticles exhibited a high photothermal effect under irradiation of a near-infrared laser due to the strong absorption of PB nanoshells, which led to more than 80% death of HeLa cells with only 0.016 mg·mL(-1) of the nanoparticles with the aid of the magnetic targeting effect. Using tumor-bearing nude mice as the model, the near-infrared laser light ablated the tumor effectively in the presence of the Fe3O4@PB nanoparticles and the tumor growth inhibition was evaluated to be 87.2%. Capabilities of MRI, magnetic targeting, and photothermal therapy were thus integrated into a single agent to allow efficient MRI-guided targeted photothermal therapy. Most importantly, both PB and Fe3O4 nanoparticles were already clinically approved drugs, so the Fe3O4@PB nanoparticles as a theranostic nanomedicine would be particularly promising for clinical applications in the human body due to the reliable biosafety.

M6A modification promotes blood-brain barrier breakdown during cerebral ischemia/reperfusion injury through increasing matrix metalloproteinase 3 expression.

Blood-brain barrier (BBB) breakdown is a critical event in cerebral ischemia-reperfusion (I/R) injury, and matrix metalloproteinases (MMPs), which are proteolytic enzymes, play essential roles in BBB breakdown through degrading the extracellular matrix. N6-Methyladenosine (m6A), the most common and reversible mRNA modification, has an important role in the progression of cerebral I/R injury. However, whether m6A is related to BBB breakdown and MMPs expression in cerebral I/R injury is still not clear. In this study, we explored the potential effects of m6A modification on BBB breakdown in cerebral I/R injury and its underlying mechanisms using mice subjected to transient middle cerebral artery occlusion and reperfusion (MCAO/R), and mouse brain endothelial cells treated with oxygen-glucose deprivation and reoxygenation (OGD/R). We find that MMP3 expression is highly expressed and positively associated with the m6A writer CBLL1 (Cbl proto-oncogene like 1) in cerebral I/R injury in vivo and in vitro. Furthermore, MMP3 mRNA occurs m6A modification in mouse brain endothelial cells, and the m6A modification level of MMP3 mRNA is significantly increased in cerebral I/R injury. Moreover, inhibition of m6A modification reduces MMP3 expression and ameliorates BBB breakdown in cerebral I/R in vivo and in vitro. In conclusion, m6A modification promotes BBB breakdown in cerebral I/R injury through increasing MMP3 expression, indicating that m6A may be a potential therapeutic target for cerebral I/R injury.

Nitrocellulose membranes in situ grown with Prussian blue nanoparticles as stable nanozyme pads for colorimetric detection of dopamine.

Prussian blue (PB) is a typical peroxidase mimic with simple preparation, low cost and high eco-friendliness, but it still has drawbacks of poor stability (e.g., decomposition in aqueous dispersions) and intrinsic optical interference (e.g., high extinction coefficient over a wide wavelength range) in colorimetric assays. Herein, we used nitrocellulose (NC) membranes as synthesis hosts of PB nanoparticles (NPs) to develop a new type of three-dimensional (3D) porous nanozyme pad. By means of an in situ synthesis route, PB NPs were uniformly grown on the surfaces of the fiber scaffolds with desirable stability, which also avoided signal interference from PB NPs owing to the easy handling of the pads in a quantitative solid state. The pads showed significant peroxidase-mimicking activity toward the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) with the output of colorimetric signals. Based on the reduction of oxidized TMB (oxTMB) by dopamine (DA), the pads were exploited for simple and quantitative colorimetric detection of DA with a limit of detection (LOD) of 0.59 µM and a satisfactory accuracy for analysis of real human urine samples. This is the first attempt at exploiting NC membranes as the synthesis hosts to develop nanozyme pads, which solves the above drawbacks of traditional PB-based peroxidase mimics and has promise for various colorimetric bioanalyses, given the structural benefits of NC membranes and their broad applications in biosensors.

A Low-Frequency MEMS Magnetoelectric Antenna Based on Mechanical Resonance.

Antenna miniaturization technology has been a challenging problem in the field of antenna design. The demand for antenna miniaturization is even stronger because of the larger size of the antenna in the low-frequency band. In this paper, we consider MEMS magnetoelectric antennas based on mechanical resonance, which sense the magnetic fields of electromagnetic waves through the magnetoelectric (ME) effect at their mechanical resonance frequencies, giving a voltage output. A 70 µm diameter cantilever disk with SiO2/Cr/Au/AlN/Cr/Au/FeGaB stacked layers is prepared on a 300 µm silicon wafer using the five-masks micromachining process. The MEMS magnetoelectric antenna showed a giant ME coefficient is 2.928 kV/cm/Oe in mechanical resonance at 224.1 kHz. In addition, we demonstrate the ability of this MEMS magnetoelectric antenna to receive low-frequency signals. This MEMS magnetoelectric antenna can provide new ideas for miniaturization of low-frequency wireless communication systems. Meanwhile, it has the potential to detect weak electromagnetic field signals.

Nomogram for Predicting Overall Survival in Acral Lentiginous Melanoma: A Population-based Study.

BACKGROUND: The objective of this study was to establish a nomogram for predicting the overall survival (OS) of patients with acral lentiginous melanoma (ALM). MATERIALS AND METHODS: The study sample was selected from 1785 patients diagnosed with ALM from 2004 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database, and R software was used to divide patients into the training cohort and validation cohort at a ratio of 7: 3. Stepwise selection method in the Cox regression model was used in the training cohort to select predictive variables to construct the nomogram, and model validation parameters were used in the validation cohort to evaluate the performance of the nomogram. RESULTS: The nomogram showed that age at diagnosis had the greatest impact on OS in patients with ALM, followed by AJCC stage, surgical treatment, SEER stage, sex, race, and marital status. The index of concordance, area under the receiver operating characteristic curve, calibration plots, net reclassification improvement, integrated discrimination improvement, and decision curve analysis demonstrate the good performance of this nomogram. CONCLUSION: The prognostic value of the nomogram is superior to that of the AJCC staging system alone, and it helps clinicians to better predict 3-, 5-, and 8-year OS in patients with ALM.

Multiplexed tri-mode visual outputs of immunoassay signals on a clip-magazine-assembled photothermal biosensing disk.

The photothermal biosensing principle is of increasing interest for point-of-care detection, but has rarely been applied in portable analytical devices in a lab-on-a-chip format. Herein, a photothermally responsive poly (methyl methacrylate) (PMMA)/paper hybrid disk (PT-Disk) was developed as a novel photothermal immunoassay device with the integration of a clip-magazine-assembled photothermal biosensing strategy. The PT-Disk consisted of a dissociative thermoresponsive hydrogel-loaded clip unit where the sandwich-type immunoreaction with an iron oxide-to-Prussian blue nanoparticle (PB NP) conversion took place and a magazine bearer for the rotational clip assembly and visual signal outputs. Upon laser irradiation of the clip-magazine-assembled PT-Disk, on-chip photothermal effect of PB NPs triggered both dose-dependent temperature elevation and the subsequent release of dye solutions from the central clip unit to surrounding magazine-bearing paper channels as the result of phase transition of the hydrogels, realizing multiplexed thermal image- and distance-based visual quantitative signal outputs in combination with the preliminary colorimetric readout on the PT-Disk. Using the multiplexed tri-mode signal outputs, the PT-Disk can quantify prostate specific antigen with limits of detection of 1.4-2.8 ng mL-1. This is the first attempt to apply the photothermal biosensing principle in portable PMMA/paper-based analytical devices, which offers not only versatile on-chip visual quantitative signal outputs, but also the implementation of the photothermal biosensing principle in a lab-on-a-chip format.

Remotely tunable microfluidic platform driven by nanomaterial-mediated on-demand photothermal pumping.

The requirement of on-demand microfluidic pumps and instrument-free readout methods remains a major challenge for the development of microfluidics. Herein, a new type of microfluidic platform, an on-demand photothermal microfluidic pumping platform, has been developed using an on-chip nanomaterial-mediated photothermal effect as novel and remotely tunable microfluidic driving force. The photothermal microfluidic pumping performance can be adjusted remotely by tuning the irradiation parameters, without changing on-chip parameters or replacing enzymes or other reagents. In contrast to graphene oxide, Prussian blue nanoparticles with higher photothermal conversion efficiency were used as the model photothermal agent to demonstrate the proof of concept. The on-chip pumping distance is linearly correlated with both the irradiation time and the nanomaterial concentration. The applications of photothermal microfluidic pumping have been demonstrated in multiplexed on-chip transport of substances, such as gold nanoparticles, and visual quantitative bar-chart detection of cancer biomarkers without using specialized instruments. Upon contact-free irradiation using a laser pointer, a strong on-chip nanomaterial-mediated photothermal effect can serve as a robust and remotely tunable microfluidic pump in a PMMA/PDMS hybrid bar-chart chip to drive ink bars in a visual quantitative readout fashion. This is the first report on a photothermal microfluidic pumping platform, which has great potential for various microfluidic applications.

Spatiotemporally Controlled Multiplexed Photothermal Microfluidic Pumping under Monitoring of On-Chip Thermal Imaging.

Intelligent contactless microfluidic pumping strategies have been increasingly desirable for operation of lab-on-a-chip devices. Herein, we present a photothermal microfluidic pumping strategy for on-chip multiplexed cargo transport in a contactless and spatiotemporally controllable fashion based on the application of near-infrared laser-driven photothermal effect in microfluidic paper-based devices (µPDs). Graphene oxide (GO)-doped thermoresponsive poly(N-isopropylacrylamide)-acrylamide hydrogels served as the photothermally responsive cargo reservoirs on the µPDs. In response to remote contactless irradiation by an 808 nm laser, on-chip phase transition of the composite hydrogels was actuated in a switchlike manner as a result of the photothermal effect of GO, enabling robust on-chip pumping of cargoes from the hydrogels to predefined arrays of reaction zones. The thermal imaging technique was employed to monitor the on-chip photothermal pumping process. The microfluidic pumping performance can be spatiotemporally controlled in a quantitative way by remotely tuning the laser power, irradiation time, and GO concentration. The pumping strategy was exemplified by FeCl3 and horseradish peroxidase as the model cargoes to implement on-chip Prussian blue- and 3,3',5,5'-tetramethylbenzidine-based colorimetric reactions, respectively. Furthermore, multiplexed on-demand microfluidic pumping was achieved by flexibly adjusting the irradiation pathway and the microfluidic pattern. The new microfluidic pumping strategy shows great promise for diverse microfluidic applications due to its flexibility, high integratability into lab-on-a-chip devices, and contactless and spatiotemporal controllability.

Theaflavin alleviates inflammatory response and brain injury induced by cerebral hemorrhage via inhibiting the nuclear transcription factor kappa ß-related pathway in rats.

OBJECTIVE: Intracerebral hemorrhage (ICH) is one of the most common acute cerebrovascular diseases with high mortality. Numerous studies have shown that inflammatory response played an important role in ICH-induced brain injury. Theaflavin (TF) extracted from black tea has various biological functions including anti-inflammatory activity. In this study, we investigated whether TF could inhibit ICH-induced inflammatory response in rats and explored its mechanism. MATERIALS AND METHODS: ICH rat models were induced with type VII collagenase and pretreated with TF by gavage in different doses (25 mg/kg-100 mg/kg). Twenty-four hours after ICH attack, we evaluated the rats' behavioral performance, the blood-brain barrier (BBB) integrity, and the formation of cerebral edema. The levels of reactive oxygen species (ROS) and inflammatory cytokines were examined by 2',7'-dichlorofluorescin diacetate and enzyme-linked immunosorbent assay. Nissl staining and transferase dUTP nick end labeling (TUNEL) were aimed to detect the neuron loss and apoptosis, the mechanism of which was explored by Western blot. RESULTS: It was found that in the pretreated ICH rats TF significantly alleviated the behavioral defects, protected BBB integrity, and decreased the formation of cerebral edema and the levels of ROS as well as inflammatory cytokines (including interleukin-1 beta [IL-1ß], IL-18, tumor nectosis factor-alpha, interferon-γ, transforming growth factor beta, and (C-X-C motif) ligand 1 [CXCL1]). Nissl staining and TUNEL displayed TF could protect against the neuron loss and apoptosis via inhibiting the activation of nuclear transcription factor kappa-ß-p65 (NF-κß-p65), caspase-1, and IL-1ß. We also found that phorbol 12-myristate 13-acetate, a nonspecific activator of NF-κß-p65, weakened the positive effect of TF on ICH-induced neural defects and neuron apoptosis by upregulating NF-κß-related signaling pathway. CONCLUSION: TF could alleviate ICH-induced inflammatory responses and brain injury in rats via inhibiting NF-κß-related pathway, which may provide a new way for the therapy of ICH.

Nanoparticle-mediated photothermal effect enables a new method for quantitative biochemical analysis using a thermometer.

A new biomolecular quantitation method, nanoparticle-mediated photothermal bioassay, using a common thermometer as the signal reader was developed. Using an immunoassay as a proof of concept, iron oxide nanoparticles (NPs) captured in the sandwich-type assay system were transformed into a near-infrared (NIR) laser-driven photothermal agent, Prussian blue (PB) NPs, which acted as a photothermal probe to convert the assay signal into heat through the photothermal effect, thus allowing sensitive biomolecular quantitation using a thermometer. This is the first report of biomolecular quantitation using a thermometer and also serves as the first attempt to introduce the nanoparticle-mediated photothermal effect for bioassays.

Controlled Drug Delivery Using Microdevices.

Therapeutic drugs administered systematically are evenly distributed to the whole body through blood circulation and have to cross many biological barriers before reaching the pathological site. Conventional drug delivery may make drugs inactive or reduce their potency as they may be hydrolyzed or degraded enzymatically and are rapidly excreted through the urinary system resulting in suboptimal concentration of drugs at the desired site. Controlled drug delivery aims to localize the pharmacological activity of the drug to the desired site at desired release rates. The advances made by micro/nanofluidic technologies have provided new opportunities for better-controlled drug delivery. Various components of a drug delivery system can be integrated within a single tiny micro/nanofluidic chip. This article reviews recent advances of controlled drug delivery made by microfluidic/nanofluidic technologies. We first discuss microreservoir-based drug delivery systems. Then we highlight different kinds of microneedles used for controlled drug delivery, followed with a brief discussion about the current limitations and the future prospects of controlled drug delivery systems.

Chitosan stabilized Prussian blue nanoparticles for photothermally enhanced gene delivery.

The lack of biosafety and insufficient delivery efficiency of gene-carriers are still obstacles to human gene therapy. This paper reported highly biocompatible chitosan (CS) functionalized Prussian blue (PB) nanoparticles (designated as CS/PB NPs) for photocontrollable gene delivery. The ultra-small size (∼3 nm), positive charge and high physiological stability of CS/PB NPs make it suitable to be a nonviral vector. In addition, CS/PB NPs could effectively convert the near infrared (NIR) light into heat due to its strong absorption in the NIR region, assisting the uptake of NPs by cells. Upon NIR light irradiation, CS/PB NPs showed superior gene transfection efficiency, much higher than that of free polyethylenimine (PEI). Both in vitro and in vivo experiments demonstrated that CS/PB NPs had excellent biocompatiblity. This work also encourages further exploration of the CS/PB NPs as a photocontrollable nanovector for combined photothermal and gene therapy.