A New Hybrid Lead-Free Metal Halide Piezoelectric for Energy Harvesting and Human Motion Sensing.

Hybrid organic-inorganic piezoelectrics have attracted attention due to their simple synthesis, mechanical flexibility, and designability, which have promising application potential in flexible sensing and self-powered energy harvesting devices. Although some hybrid piezoelectrics are discovered, most of their structures are limited by the perovskite-type and often contain lead. Herein, the synthesis, structure, and piezoelectric properties of a new hybrid lead-free metal halide, (BTMA)2 CoBr4 (BTMA = benzyltrimethylammonium) are reported. The experimental and theoretical results demonstrate that this material simply composed of [CoBr4 ]2- tetrahedra and BTMA+ cations exhibits significant piezoelectricity (d22 = 5.14, d25 = 12.40 pC N-1 ), low Young's and shear moduli (4.11-17.56 GPa; 1.86-7.91 GPa). Moreover, the (BTMA)2 CoBr4 /PDMS (PDMS = polydimethylsiloxane) composite thin films are fabricated and optimized. The 10% (BTMA)2 CoBr4 /PDMS-based flexible devices show attractive performance in energy harvesting with an open-circuit voltage of 19.70 V, short-circuit current of 4.24 µA, and powder density of 11.72 µW cm-2 , catching up with those of piezoelectric ceramic composites. Meanwhile, these film devices show excellent capability in accurately sensing human body motions, such as finger bending and tapping. This work demonstrates that (BTMA)2 CoBr4 and related piezoelectric lead-free halides can be promising molecular materials in modern energy and sensing applications.

Different Types of Circulatory Inflammatory Biomarkers Associated with Cerebral Arterial Atherosclerosis and Dolichoectasia.

BACKGROUND: Although inflammation is found to be related to arteriopathy pathogenesis, it is yet to be determined the distinct correlations of specific inflammatory biomarker types contributing to different cerebral large vessel diseases. We aimed to investigate the association between multiple inflammatory biomarkers and cerebral atherosclerosis and dolichoectasia in a community-based sample. METHODS: A total of 960 participants of the Shunyi study were included. A panel of 14 circulatory inflammatory biomarkers was assessed and then grouped in three sets as systemic, endothelial-related, and media-related inflammation, based on underlying different inflammatory cascades. Intracranial atherosclerotic stenosis (ICAS), dolichoectasia estimated by magnetic resonance angiography, and carotid plaques estimated by ultrasound were also performed. RESULTS: Endothelial-related inflammatory group was related to the presence of ICAS (R2 = 0.215, p = 0.024) and carotid plaques (R2 = 0.342, p = 0.013). Backward stepwise elimination showed that E-selectin was prominent (ß = 0.67, 95% CI: 0.54-0.85, p = 0.001; ß = 0.79, 95% CI: 0.68-0.93, p = 0.005). Systemic inflammatory group was associated with an increased basilar artery diameter (R2 = 0.051, p < 0.001), and backward stepwise elimination showed that IL-6 was prominent (ß = 0.07, 95% CI: 0.03-0.11, p < 0.001). CONCLUSION: Different types of inflammatory biomarkers were associated with atherosclerosis and dolichoectasia, respectively, implying dissimilar inflammatory processes. Further confirming of their distinct anti-inflammatory roles as potential therapeutic targets is warrant.

Coupling a droplet generator with conventional ESI-MS for quantitative analysis of small-volume samples.

Quantitative mass spectrometric analysis of small-volume samples (e.g., < 1 µL) has been a challenge mainly due to the difficulties with sample handling and its injection into the system for analysis. Herein we report a microfluidic analytical platform coupling a droplet generator with conventional electrospray ionization-mass spectrometry (ESI-MS) that enables multiple analyses of a µL-sized sample with sensitivity and repeatability. In an analysis by droplet generator-assisted ESI-MS (DG-ESI-MS), a sample of µL volume is pulled into a sampling capillary and its equal nL-sized portions are generated by a droplet generator and analyzed by ESI-MS at time intervals of choice. The droplet generator is made of PMMA sheets by laser engraving conveniently and at a low cost. In a study to achieve effective ESI-MS detection of water-in-oil droplets, it's found that the problem of MS signal suppression by oil can be solved by using an appropriate organic carrier with ESI-enhancing additives. The proposed DG-ESI-MS method has linear calibration curves for both adenine and phenylalanine with LODs at the sub-µM level. Application of the present analytical platform for monitoring substrate concentration changes in an enzymatic reaction solution of 3 µL is demonstrated.

Ligand fishing based on tubular microchannel modified with monoamine oxidase B for screening of the enzyme's inhibitors from Crocus sativus and Edgeworthia gardneri.

A novel strategy of performing ligand fishing with enzyme-modified open tubular microchannel was proposed for screening bioactive components present in medicinal plants. Monoamine oxidase B was immobilized onto the surface of the microchannel for the first time to specifically extract its ligands when the plant's extracts solution flows through the channel. The thermal and the storage stability of immobilized monoamine oxidase B were significantly enhanced after immobilization. Crocin I and Ⅱ were extracted from Crocus sativus, and tiliroside was extracted from Edgeworthia gardneri. All the three compounds were inhibitors of the enzyme with the half-maximal inhibitory concentration values of 26.70 ±â€¯0.91, 19.88 ±â€¯2.78, and 15.65 ± 0.85 µM, respectively. The enzyme inhibition kinetics and molecular docking were investigated. This is the first report on the inhibitory effects of tiliroside and crocin Ⅱ. The novel ligand fishing method proposed in this work possesses advantages of rapidness, high efficiency, and tiny sample consumption compared to routine ligand fishing, with promising potential for screening active natural products in complex mixtures.

3D parametric surface planar topological guide plate to create a PMSG for the emergency endovascular repair of an aortic arch aneurysm.

A 69-year-old male patient was admitted by 10 h severe chest pain. Computed tomography angiography showed a 7.3 cm aneurysm of the aortic arch. We used a three-dimensional parametric surface planar topological guide plate to prepare a guide plate in 40 min. The plate was used to localize the opening of the aortic arch branches on table to create a physician-modified stent graft (PMSG). The aneurysm was successfully repaired by the triple inner branched PMSG, with no endoleak and all the branched arteries patency in follow-up. This technique could not only make accurate fenestration but also meet the need for emergency surgery.

One-dimensional cobalt oxide nanotubes with rich defect for oxygen evolution reaction.

For the electrochemcial hydrogen production, the oxygen evolution reaction (OER) is a pivotal half-reaction in water splitting. However, OER suffers sluggish kinetics and high overpotential, leading to the increase of overall energy consumption and decrease of the energy efficiency. In this work, high-quality cobalt oxide porous nanotubes (Co3O4-PNTs) are easily obtained by simple self-template approach. One-dimensional (1D) porous structure provides the large specific surface area, enough abundant active atoms and effective mass transfer. In addition, Co3O4-PNTs also own self-stability of 1D architecture, benefitting the their durability for electrocatalytic reaction. Thus, Co3O4-PNTs with optimal annealing temperature and time reveal the attractive alkaline OER performance (Tafel slope of 56 mV dec-1and 323 mV overpotential at 10 mA cm-2), which outperform the Co3O4nanoparticles and benchmark commercial RuO2nanoparticles. Furthermore, Co3O4-PNTs also exhibit excellent OER durability for least 10 h at the 10 mA cm-2. Overall, Co3O4-PNTs with low cost can be serve as a highly reactive and economical catalyst for OER.

Lower normal free thyroxine is associated with a higher risk of metabolic syndrome: a retrospective cohort on Chinese population.

BACKGROUND: Recently, the relationship between thyroid hormones (THs) across the euthyroid ranges and metabolic syndrome (MetS) has been widely discussed. This study aimed to present specific cutoff values of THs to assess the association between THs and MetS in a euthyroid cohort. METHODS: Data of 2694 subjects, aged 18-80 years, who attended health examination in Xi'an Electric Power Central Hospital from April 2011 to December 2015 were collected and analyzed. The first cohort enrolled 929 participants (followed up by 2221 person-years totally) to assess correlations between serum thyrotropin (TSH), triiodothyronine (T3), thyroxine (T4) levels and MetS. The second cohort included 698 participants (followed up by 1709 person-years totally) to evaluate relationships between serum free triiodothyronine (FT3), free thyroxine (FT4) levels and MetS. MetS was defined according to the criteria of the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) scientific statements of 2009. Euthyroidism was defined as serum TSH, FT3 and FT4 levels within the reference ranges without taking any thyroid medication. RESULTS: The cutoff values for TSH, T3, T4, FT3 and FT4 were 2.0mIU/L, 1.9 nmol/L, 117 nmol/L, 4.3 pmol/L and 16 pmol/L, respectively. Participants were categorized into two groups according to cutoff values: the lower-THs group and the higher-THs group. There was no significant difference in the risk of MetS between two groups in TSH, T3, T4 and FT3. The incidence of MetS was significantly higher in lower-FT4 group than higher-FT4 group (1.00 vs 0.622 (0.458, 0.846), P = 0.002). The lower-FT4/higher-TSH group had the highest hazard ratios of MetS. (2.131vs 1.0 (1.380,3.291), P = 0.006). CONCLUSIONS: Lower normal FT4 (FT4 ≤ 16.0 pmol/L) is an independent risk factor for MetS, and lower normal thyroid function (TSH > 2.0 mIU/L and FT4 ≤ 16.0 pmol/L) is associated with a higher risk of developing MetS.

A New One-Pot Fluorescence Derivatization Strategy for Highly Sensitive MicroRNA Analysis.

MicroRNAs (miRNAs) modulate the expression of over 30 % of mammalian genes during development and apoptosis, and abnormal expression of miRNAs may lead to a range of human pathologies. Therefore, analysis of miRNAs is valuable for disease diagnostics. In this work, a novel one-pot fluorescence derivatization strategy was developed for miRNA analysis. The mechanism of the derivatization reaction was explored by using instrumental methods, including liquid chromatography, fluorescence spectroscopy, and mass spectrometry. Highly fluorescent N6 -ethenoadenine (ϵ-adenine) was formed and detached from the miRNA sequence through the reaction of adenine in nucleic acids with 2-chloroacetaldehyde (CAA) at 100 °C. This is the first experimental evidence that the cooperation of formed ϵ-adenine and water-mediated hydrogen-bond interaction between the proton at the 2'- and the oxyanion at 3'-positions stabilized the oxocarbenium significantly, which makes the depurination and derivatization of miRNA highly effective. Based on this derivatization strategy, a facile and sensitive high-performance liquid chromatography method was developed for quantitative assay of miRNAs. In combination with magnetic solid-phase extraction (MSPE), the HPLC method was shown to be useful for the determination of microRNAs at sub-picomolar level in serum samples.

Mass spectrometric quantification of microRNAs in biological samples based on multistage signal amplification.

This work describes a novel method for quantification of miRNAs based on multistage signal amplification (MSA) and liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The multistage signal amplification involves hybridization enrichment of miRNA targets with a DNA probe-magnetic bead conjugate, target recycling amplification with a duplex-specific nuclease, and acid hydrolysis of the reporter molecules producing free nucleobases. Nucleobases thus generated are quantified by LC-ESI-MS/MS with specificity and repeatability. Taking miR-21 as the model target, biological samples such as serum and cell cultures were analyzed by using the present protocol. The analytical results indicate that facile and cost-effective quantifications of miRNA targets can be achieved by using the popular LC-ESI-MS/MS technique, and very importantly, without an isolation of total RNAs from the sample prior to the quantitative assay. The assay for miR-21 detection had a linear calibration curve in the range from 0.2 pM to 0.25 nM with a limit of detection of 60 fM. Analysis of MCF-7 cells treated with toremifene (a potent inhibitor of breast cancer cell growth) revealed that the content of miRNA-21 decreased by ca. 50%, and the decrease was dose-dependent.

Fast quantification of free amino acids in food by microfluidic voltage-assisted liquid desorption electrospray ionization-tandem mass spectrometry.

A method based on microfluidic voltage-assisted liquid desorption electrospray ionization-tandem mass spectrometry (VAL-DESI-MS/MS) has been developed for fast quantification of free amino acids in food. Food extracts were transferred to the microfluidic platform and analyzed by liquid desorption ESI-MS/MS. Deuterated aspartic acid (i.e., 2,2,3-d3-Asp) was used as internal standard for analysis. The method had linear calibration curves with r2 values > 0.998. Limits of detection were at the level of sub µM for the amino acids tested, i.e., glutamic acid (Glu), arginine (Arg), tyrosine (Tyr), tryptophan (Trp), and phenylalanine (Phe). To validate the proposed method in food analysis, extracts of Cordyceps fungi were analyzed. Amino acid contents were found in the range from 0.63 mg/g (Tyr in Cordyceps sinensis) to 4.44 mg/g (Glu in Cordyceps militaris). Assay repeatability (RSD) was ≤ 5.2% for all the five amino acids measured in all the samples analyzed. Recovery was found in the range from 95.8 to 105.1% at two spiking concentrations of 0.250 mg/g and 1.00 mg/g. These results prove that the proposed microfluidic VAL-DESI-MS/MS method offers a quick and convenient means of quantifying free amino acids with accuracy and repeatability. Therefore, it may have potential in food analysis for nutritional and quality assessment purposes. Graphical abstract.

Single-Pixel Imaging with Origami Pattern Construction.

Single-pixel compressive imaging can recover images from fewer measurements, offering many benefits especially for the imaging modalities where array detection is unavailable. However, the widely used random projections fail to explore internal relations between coding patterns and image reconstruction. Here, we propose a single-pixel imaging method based on a deterministic origami pattern construction that can lead to a more accurate pattern ordering sequence and better imaging quality. It can decrease the sampling ratio, closer to the upper bounds. The experimental realization of this approach is a big step forward towards practical applications.

[Meta Analysis of Risks of Cardiocerebral Vascular Events in Patients with Primary Biliary Cholangitis].

To systematically evaluate the risks of cardiocerebral vascular events in patients with primary biliary cholangitis(PBC). Methods We carried out a Meta analysis by RevMan 5.3 software to investigate literatureon the risk of cardiocerebral vascular events in patients with PBC and controls. Results Compared with non-PBC controls,PBC patients had significantly higher risk of coronary events(RR=1.56,P=0.0002);however,the risk of cerebrovascular events showed no significant difference between these two groups(RR=1.01,P=0.94).Subgroup analysis demonstrated a significantly lower risk of transient ischemic attack or carotid stenosis in PBC patients(RR=0.63,P=0.03);however,there was no significant difference in the risk of stroke(RR=1.11,P=0.40). Conclusion Patients with PBC have an increased risk of coronary events but may have a lower risk of transient ischemic attack or carotid stenosis.

Quantification of MicroRNAs by Coupling Cyclic Enzymatic Amplification with Microfluidic Voltage-Assisted Liquid Desorption Electrospray Ionization Mass Spectrometry.

Quantitative assay of microRNAs (miRNAs) with mass spectrometric detection currently suffers from two major disadvantages, i.e., being insufficient in sensitivity and requiring an extraction or chromatographic separation prior to MS detection. In this work, we developed a facile and sensitive assay of targeted miRNAs based on the combination of cyclic enzymatic amplification (CEA) with microfluidic voltage-assisted liquid desorption electrospray ionization tandem mass spectrometry (VAL-DESI-MS/MS). The single-stranded DNA (ssDNA) probe was designed to have a sequence complementary to the miRNA target with an extension of a two-base nucleotide fragment (i.e., CpC) at the 3'-position as MS signal reporter, thus being easy to prepare and high in stability. In the proposed CEA-VAL-DESI-MS/MS assay, an ssDNA probe was added to a sample solution, forming a DNA-miRNA hybrid. Duplex-specific nuclease (DSN) was then added to cleave specifically the DNA probe in the heteroduplex strands. As the hybridization-cleavage cycle repeated itself for many rounds, a large quantity of CpC molecules was produced that was quantified by VAL-DESI-MS/MS with accuracy and specificity. miRNA-21 was tested as the model target. The assay had a linear calibration equation in the range from 2.5 pM to 1.0 nM with a limit of detection of 0.25 pM. Determination of miRNA-21 in cellular samples was demonstrated. miRNA-21 was found to be 95.3 ± 13.95 amol ( n = 3) in 100 mouse peritoneal macrophages with a recovery of 94.2 ± 2.6% ( n = 3). Interestingly, analysis of exosomes secreted from these cells revealed that exposure of the cells to chemical stimuli caused a 3-fold increase in exosomal level of miRNA-21. The results suggest that the proposed assay may provide an accurate and cost-effective means for quantification of targeted miRNAs in biomedical samples.

Rapid quantification of aloin A and B in aloe plants and aloe-containing beverages, and pharmaceutical preparations by microchip capillary electrophoresis with laser induced fluorescence detection.

A microchip capillary electrophoresis coupled with laser induced fluorescence detection method for the fast determination of aloin was developed and comprehensively applied for the quantification of aloin A and B present in seven aloe plant species, 42 aloin-containing crude drugs, ten aloe pharmaceutical preparations, and four aloe gel-containing functional foods. The excitation and emission wavelengths for detection of both aloins were set at 473 and 520 nm, respectively. Sample analysis on a 35 mm length of glass microchip channel was completed within 40 s. An interference study indicated that the other main anthraquinones present in the samples did not interrupt with the target aloins detection, demonstrating the good selectivity of this method. It is demonstrated that this method is fast, facile, and specific for determination of aloin A and B from matrix samples which can be applied to the quality control of a wide varieties of aloe species and aloe-derived products.

Well-Aligned Au/TiO2 Nanorods by Magnetron Sputtering with Enhanced Photocatalytic Properties.

In this work, we demonstrate the feasibility of preparing Au/TiO2 nanorods via a dc magnetron sputtering at room temperature and heat-treatment at 500 °C in air for 2 h. The heat treatment leads to the migration of Au atoms into TiO2 nanofilm to form Au/TiO2 nanorods with Au nanoparticles embedded in the TiO2 nanorods of anatase phase. The Au nanoparticles in the TiO2 nanorods suppress the charge recombination. These Au/TiO2 nanorods showed high absorption and intensive response to the visible light and had improved photocatalytic properties in comparison with pure TiO2 nanoparticles formed by using similar method.

Late-onset cobalamin C deficiency Chinese sibling patients with neuropsychiatric presentations.

The Cobalamin C deficiency (cblC), characterized with elevated methylmalonic acidemia and homocystinuria in plasma, is an inborn error of cobalamin metabolism. The late-onset cblC siblings patients were rarely reported. In this study, we analyzed the clinical presentations and treatment outcomes of late-onset cblC in Chinese sibling patients with neuropsychiatric presentations. The clinical data of four pairs of Chinese patients were retrospectively analyzed. Serum homocysteine, urine organic acids measurements, neuroimaging exams and gene analysis were carried out in all patents. Patients were reevaluated after treatments with cobalamin, folate, betaine, L-carnitine and compound vitamin B. The mean age at disease onset was 13.7 (range 2-19) years. The neuropsychiatric disturbances including cognitive decline (3/8), psychiatric disturbances (4/8), gait instability (2/8), lower extremity weakness and numbness (3/8) and thromboembolic events (1/8). Two patients suffered nephropathy. The mean serum homocysteine when patients were diagnosed was 109.4 (range 69.5-138) µM/L. The abnormal radioimaging included scoliosis by X-ray (5/6), cerebral atrophy (4/6) and spinal cord atrophy (3/6) by MRI scan. Three pairs of siblings showed heterozygous mutations of MMACHC gene including c.482G > A (4/6), c.354G > C (2/6), c.570insT (2/6), c.445_446del (2/6) and c.656_4658del (2/6). The other two siblings showed homozygous mutation with c.452A > G in MMACHC gene. After treatments, the psychiatric symptoms were obviously relieved in all the patients. In Chinese siblings with late-onset cblC, the main clinic manifestation and abnormal radioimaging were cognitive decline and cerebral atrophy respectively. The most common gene mutation was c.482G > A of MMACHC gene. The patients responded well to the treatments.

Spectroscopic investigation of the anticancer alkaloid piperlongumine binding to human serum albumin from the viewpoint of drug delivery.

Piperlongumine (PL) is a very promising natural agent with a high potential for cancer treatment. To overcome the poor water solubility of PL, there is a need to develop a novel water-soluble formulation in which PL is non-covalently bound to human serum albumin (HSA). PL binding to HSA was studied by various spectroscopic techniques under simulated physiological conditions. Spectroscopic evidence showed that the interaction of PL with HSA could form a PL-HSA complex. The binding constant (Ka ) values increased with increasing temperature, and a similar dependence was observed for the number of binding sites (n) values. The number of PL molecules bound to HSA reached 8.1 when the temperature was raised to 308 K. Thermodynamic calculation results suggested that the binding reaction occurred spontaneously but was an entropy-driven process, and hydrophobic forces played a major role in stabilizing the complex. Furthermore, PL binding induced conformational and microenvironmental changes in HSA. Displacement studies indicated that PL and warfarin had separate binding regions in site I. Therefore, it would be possible to develop a novel water-soluble formulation involving PL and HSA. This study may provide some valuable information in terms of improving the poor water solubility of PL.

Direct Analysis of Biofluids by Mass Spectrometry with Microfluidic Voltage-Assisted Liquid Desorption Electrospray Ionization.

Signal suppression by sample matrix in direct electrospray ionization-mass spectrometric (ESI-MS) analysis hampers its clinical and biomedical applications. We report herein the development of a microfluidic voltage-assisted liquid desorption electrospray ionization (VAL-DESI) source to overcome this limitation. Liquid DESI is achieved for the first time in a microfluidic format. Direct analysis of urine, serum, and cell lysate samples by using the proposed microfluidic VAL-DESI-MS/MS method to detect chemical compounds of biomedical interest, including nucleosides, monoamines, amino acids, and peptides is demonstrated. Analyzing a set of urine samples spiked with dihydroxyphenylalanine (DOPA) showed that the assay had a linear calibration curve with r2 value of 0.997 and a limit of detection of 0.055 µM DOPA. The method was applied to simultaneous quantification of nucleosides, that is, cytidine, adenosine, uridine, thymidine, and guanosine in cell lysates using 8-bromoadenosine as internal standard. Adenosine was found most abundant at 26.5 ± 0.57 nmol/106 cells, while thymidine was least at 3.1 ± 0.31 nmol/106 cells. Interestingly, the ratio of adenosine to deoxyadenosine varied significantly from human red blood cells (1.07 ± 0.06) to cancerous cells, including lymphoblast TK6 (0.52 ± 0.02), skin melanoma C32 (0.82 ± 0.04), and promyelocytic leukemia NB4 cells (0.38 ± 0.06). These results suggest that the VAL-DESI-MS/MS technique has a good potential in direct analysis of biofluids. Further, because of the simplicity in its design and operation, the proposed microfluidic liquid DESI source can be fabricated as a disposable device for point-of-care measurements.

Persistency of Enlarged Autolysosomes Underscores Nanoparticle-Induced Autophagy in Hepatocytes.

The diverse biological effects of nanomaterials form the basis for their applications in biomedicine but also cause safety issues. Induction of autophagy is a cellular response after nanoparticles exposure. It may be beneficial in some circumstances, yet autophagy-mediated toxicity raises an alarming concern. Previously, it has been reported that upconversion nanoparticles (UCNs) elicit liver damage, with autophagy contributing most of this toxicity. However, the detailed mechanism is unclear. This study reveals persistent presence of enlarged autolysosomes in hepatocytes after exposure to UCNs and SiO2 nanoparticles both in vitro and in vivo. This phenomenon is due to anomaly in the autophagy termination process named autophagic lysosome reformation (ALR). Phosphatidylinositol 4-phosphate (PI(4)P) relocates onto autolysosome membrane, which is a key event of ALR. PI(4)P is then converted into phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2 ) by phosphatidylinositol-4-phosphate 5-kinase. Clathrin is subsequently recruited by PI(4,5)P2 and leads to tubule budding of ALR. Yet it is observed that PI(4)P cannot be converted in nanoparticle-treated hepatocytes cells. Exogenous supplement of PI(4,5)P2 suppresses the enlarged autolysosomes in vitro. Abolishment of these enlarged autolysosomes by autophagy inhibitor relieves the hepatotoxicity of UCNs in vivo. The results provide evidence for disrupted ALR in nanoparticle-treated hepatocytes, suggesting that the termination of nanoparticle-induced autophagy is of equal importance as the initiation.

Microfluidic Platform with In-Chip Electrophoresis Coupled to Mass Spectrometry for Monitoring Neurochemical Release from Nerve Cells.

Chemical stimulus-induced neurotransmitter release from neuronal cells is well-documented. However, the dynamic changes in neurochemical release remain to be fully explored. In this work, a three-layered microfluidic chip was fabricated and evaluated for studying the dynamics of neurotransmitter release from PC-12 cells. The chip features integration of a nanoliter sized chamber for cell perfusion, pneumatic pressure valves for fluidic control, a microfluidic channel for electrophoretic separation, and a nanoelectrospray emitter for ionization in MS detection. Deploying this platform, a microchip electrophoresis-mass spectrometric method (MCE-MS) was developed to simultaneously quantify important neurotransmitters, including dopamine (DA), serotonin (5-HT), aspartic acid (Asp), and glutamic acid (Glu) without need for labeling or enrichment. Monitoring neurotransmitter release from PC-12 cells exposed to KCl (or alcohol) revealed that all four neurotransmitters investigated were released. Two release patterns were observed, one for the two monoamine neurotransmitters (i.e., DA and 5-HT) and another for the two amino acid neurotransmitters. Release dynamics for the two monoamine neurotransmitters was significantly different. The cells released DA most quickly and heavily in response to the stimulation. After exposure to the chemical stimulus for 4 min, the DA level in the perfusate from the cells was 86% lower than that at the beginning. Very interestingly, the cells started to release 5-HT in large quantities when they stopped releasing DA. These results suggest that DA and 5-HT are packaged into different vesicle pools and they are mobilized differently in response to chemical stimuli. The microfluidic platform proposed is proven useful for monitoring cellular release in biological studies.