Portable in situ temperature-dependent spectroscopy on a low-cost microfluidic platform integrated with a battery-powered thermofoil heater.

A low-cost microfluidic platform integrated with a flexible heater was developed for in situ temperature-dependent spectroscopic measurement at the point of care. After verifying the system by comparing on-chip spectroscopic measurement of methylene blue with the conventional spectroscopy, we demonstrated its applications in temperature-dependent absorption spectroscopy of a model biomolecule, curcumin. The system is portable, battery-powered and requires ultra-low volumes of analytes, which is highly suitable for point-of-care characterization.

Ultrasensitive detection of acephate based on carbon quantum dot-mediated fluorescence inner filter effects.

Acephate is an organophosphorus pesticide (OP) that is widely used to control insects in agricultural fields such as in vegetables and fruits. Toxic OPs can enter human and animal bodies and eventually lead to chronic or acute poisoning. However, traditional enzyme inhibition and colorimetric methods for OPs detection usually require complicated detection procedures and prolonged time and have low detection sensitivity. High-sensitivity monitoring of trace levels of acephate residues is of great significance to food safety and human health. Here, we developed a simple method for ultrasensitive quantitative detection of acephate based on the carbon quantum dot (CQD)-mediated fluorescence inner filter effect (IFE). In this method, the fluorescence from CQDs at 460 nm is quenched by 2,3-diaminophenazine (DAP) and the resulting fluorescence from DAP at 558 nm is through an IFE mechanism between CQDs and DAP, producing ratiometric responses. The ratiometric signal I558/I460 was found to exhibit a linear relationship with the concentration of acephate. The detection limit of this method was 0.052 ppb, which is far lower than the standards for acephate from China and EU in food safety administration. The ratiometric fluorescence sensor was further validated by testing spiked samples of tap water and pear, indicating its great potential for sensitive detection of trace OPs in complex matrixes of real samples.

A microfluidic fully paper-based analytical device integrated with loop-mediated isothermal amplification and nano-biosensors for rapid, sensitive, and specific quantitative detection of infectious diseases.

Bacterial meningitis, an infection of the membranes (meninges) and cerebrospinal fluid (CSF) surrounding the brain and spinal cord, is one of the major causes of death and disability worldwide. Higher case-fatality rates and short survival times have been reported in developing countries. Hence, a quick, straightforward, and low-cost approach is in great demand for the diagnosis of meningitis. In this research, a microfluidic fully paper-based analytical device (µFPAD) integrated with loop-mediated isothermal amplification (LAMP) and ssDNA-functionalized graphene oxide (GO) nano-biosensors was developed for the first time for a simple, rapid, low-cost, and quantitative detection of the main meningitis-causing bacteria, Neisseria meningitidis (N. meningitidis). The results can be successfully read within 1 hour with the limit of detection (LOD) of 6 DNA copies per detection zone. This paper device also offers versatile functions by providing a qualitative diagnostic analysis (i.e., a yes or no answer), confirmatory testing, and quantitative analysis. These features make the presented µFPAD capable of a simple, highly sensitive, and specific diagnosis of N. meningitis. Furthermore, this microfluidic approach has great potential in the rapid detection of a wide variety of different other pathogens in low-resource settings.

Immunotherapy discovery on tumor organoid-on-a-chip platforms that recapitulate the tumor microenvironment.

Cancer immunotherapy has achieved remarkable success over the past decade by modulating patients' own immune systems and unleashing pre-existing immunity. However, only a minority of cancer patients across different cancer types are able to benefit from immunotherapy treatment; moreover, among those small portions of patients with response, intrinsic and acquired resistance remains a persistent challenge. Because the tumor microenvironment (TME) is well recognized to play a critical role in tumor initiation, progression, metastasis, and the suppression of the immune system and responses to immunotherapy, understanding the interactions between the TME and the immune system is a pivotal step in developing novel and efficient cancer immunotherapies. With unique features such as low reagent consumption, dynamic and precise fluid control, versatile structures and function designs, and 3D cell co-culture, microfluidic tumor organoid-on-a-chip platforms that recapitulate key factors of the TME and the immune contexture have emerged as innovative reliable tools to investigate how tumors regulate their TME to counteract antitumor immunity and the mechanism of tumor resistance to immunotherapy. In this comprehensive review, we focus on recent advances in tumor organoid-on-a-chip platforms for studying the interaction between the TME and the immune system. We first review different factors of the TME that recent microfluidic in vitro systems reproduce to generate advanced tools to imitate the crosstalk between the TME and the immune system. Then, we discuss their applications in the assessment of different immunotherapies' efficacy using tumor organoid-on-a-chip platforms. Finally, we present an overview and the outlook of engineered microfluidic platforms in investigating the interactions between cancer and immune systems, and the adoption of patient-on-a-chip models in clinical applications toward personalized immunotherapy.

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.

Aptamer-functionalized metal-organic frameworks (MOFs) for biosensing.

As a class of crystalline porous materials, metal-organic frameworks (MOFs) have attracted increasing attention. Due to the nanoscale framework structure, adjustable pore size, large specific surface area, and good chemical stability, MOFs have been applied widely in many fields such as biosensors, biomedicine, electrocatalysis, energy storage and conversions. Especially when they are combined with aptamer functionalization, MOFs can be utilized to construct high-performance biosensors for numerous applications ranging from medical diagnostics and food safety inspection, to environmental surveillance. Herein, this article reviews recent innovations of aptamer-functionalized MOFs-based biosensors and their bio-applications. We first briefly introduce different functionalization methods of MOFs with aptamers, which provide a foundation for the construction of MOFs-based aptasensors. Then, we comprehensively summarize different types of MOFs-based aptasensors and their applications, in which MOFs serve as either signal probes or signal probe carriers for optical, electrochemical, and photoelectrochemical detection, with an emphasis on the former. Given recent substantial research interests in stimuli-responsive materials and the microfluidic lab-on-a-chip technology, we also present the stimuli-responsive aptamer-functionalized MOFs for sensing, followed by a brief overview on the integration of MOFs on microfluidic devices. Current limitations and prospective trends of MOFs-based biosensors are discussed at the end.

Phenolic lipids as unique bioactive compounds: a comprehensive review on their multifunctional activity toward the prevention of Alzheimer's disease.

Phenolic lipids are multifunctional compounds which play an important biological role in the body. Their unique biologic functionality stems from their strong amphiphilic character which allows them to be incorporated in erythrocytes. Through membrane incorporation, these compounds exert their biological effects on neurons which are not modulated by hydrophilic compounds. These bioactive compounds are present in nature as secondary plant metabolites, and consequently their availability is limited, for dietary and medical purposes. In this review, the pathways and mechanisms associated with the pathogenesis of Alzheimer's disease will be described. In addition, the modulatory effects of phenolic lipids on these pathways and a list of several synthetic, semi synthetic and natural sources of phenolic lipids will be examined as having the potential to prevent or combat Alzheimer's disease.

Fusion of acoustic sensing and deep learning techniques for apple mealiness detection.

Mealiness in apple fruit can occur during storage or because of harvesting in an inappropriate time; it degrades the quality of the fruit and has a considerable role in the fruit industry. In this paper, a novel non-destructive approach for detection of mealiness in Red Delicious apple using acoustic and deep learning techniques was proposed. A confined compression test was performed to assign labels of mealy and non-mealy to the apple samples. The criteria for the assignment were hardness and juiciness of the samples. For the acoustic measurements, a plastic ball pendulum was used as the impact device, and a microphone was installed near the sample to record the impact response. The recorded acoustic signals were converted to images. Two famous pre-trained convolutional neural networks, AlexNet and VGGNet were fine-tuned and employed as classifiers. According to the result obtained, the accuracy of AlexNet and VGGNet for classifying the apples to the two categories of mealy and non-mealy apples was 91.11% and 86.94%, respectively. In addition, the training and classification speed of AlexNet was higher. The results indicated that the suggested method provides an effective and promising tool for assessment of mealiness in apple fruit non-destructively and inexpensively.

A low-cost microfluidic platform for rapid and instrument-free detection of whooping cough.

Whooping cough also called Pertussis is a highly contagious respiratory infection that affects all age populations. Given recent pertussis outbreaks, there is an urgent need for a point-of-care (POC) device for rapid diagnosis of pertussis. Herein, we report a low-cost microfluidic POC device integrated with loop-mediated isothermal amplification (LAMP) technique for the rapid and accurate diagnosis of pertussis. The 3D-printed bioanalyzer housed not only the biochip but also an in-house-developed portable and fully battery-powered heater for rapid POC detection of pertussis, without the need of external electricity. The fluorescence-based results could be rapidly visualized in about one hour by the naked eye without the need for any additional instrumentation. In addition, a simple centrifuge-free sample preparation process was optimized for the efficient lysis of pertussis samples and successfully used for direct detection of bacteria in nasopharyngeal samples. High sensitivity, with a limit of detection (LOD) of 5 DNA copies per LAMP zone, and high specificity were demonstrated. We envision that the microfluidic POC device can be used in various venues such as medical clinics, schools, and other low-resource settings for the fast detection of pertussis.

Recent advances in microfluidic platforms for single-cell analysis in cancer biology, diagnosis and therapy.

Understanding molecular, cellular, genetic and functional heterogeneity of tumors at the single-cell level has become a major challenge for cancer research. The microfluidic technique has emerged as an important tool that offers advantages in analyzing single-cells with the capability to integrate time-consuming and labour-intensive experimental procedures such as single-cell capture into a single microdevice at ease and in a high-throughput fashion. Single-cell manipulation and analysis can be implemented within a multi-functional microfluidic device for various applications in cancer research. Here, we present recent advances of microfluidic devices for single-cell analysis pertaining to cancer biology, diagnostics, and therapeutics. We first concisely introduce various microfluidic platforms used for single-cell analysis, followed with different microfluidic techniques for single-cell manipulation. Then, we highlight their various applications in cancer research, with an emphasis on cancer biology, diagnosis, and therapy. Current limitations and prospective trends of microfluidic single-cell analysis are discussed at the end.

Recent advances of controlled drug delivery using microfluidic platforms.

Conventional systematically-administered drugs distribute evenly throughout the body, get degraded and excreted rapidly while crossing many biological barriers, leaving minimum amounts of the drugs at pathological sites. Controlled drug delivery aims to deliver drugs to the target sites at desired rates and time, thus enhancing the drug efficacy, pharmacokinetics, and bioavailability while maintaining minimal side effects. Due to a number of unique advantages of the recent microfluidic lab-on-a-chip technology, microfluidic lab-on-a-chip has provided unprecedented opportunities for controlled drug delivery. Drugs can be efficiently delivered to the target sites at desired rates in a well-controlled manner by microfluidic platforms via integration, implantation, localization, automation, and precise control of various microdevice parameters. These features accordingly make reproducible, on-demand, and tunable drug delivery become feasible. On-demand self-tuning dynamic drug delivery systems have shown great potential for personalized drug delivery. This review presents an overview of recent advances in controlled drug delivery using microfluidic platforms. The review first briefly introduces microfabrication techniques of microfluidic platforms, followed by detailed descriptions of numerous microfluidic drug delivery systems that have significantly advanced the field of controlled drug delivery. Those microfluidic systems can be separated into four major categories, namely drug carrier-free micro-reservoir-based drug delivery systems, highly integrated carrier-free microfluidic lab-on-a-chip systems, drug carrier-integrated microfluidic systems, and microneedles. Microneedles can be further categorized into five different types, i.e. solid, porous, hollow, coated, and biodegradable microneedles, for controlled transdermal drug delivery. At the end, we discuss current limitations and future prospects of microfluidic platforms for controlled drug delivery.

Predicting the Valence of a Scene from Observers' Eye Movements.

Multimedia analysis benefits from understanding the emotional content of a scene in a variety of tasks such as video genre classification and content-based image retrieval. Recently, there has been an increasing interest in applying human bio-signals, particularly eye movements, to recognize the emotional gist of a scene such as its valence. In order to determine the emotional category of images using eye movements, the existing methods often learn a classifier using several features that are extracted from eye movements. Although it has been shown that eye movement is potentially useful for recognition of scene valence, the contribution of each feature is not well-studied. To address the issue, we study the contribution of features extracted from eye movements in the classification of images into pleasant, neutral, and unpleasant categories. We assess ten features and their fusion. The features are histogram of saccade orientation, histogram of saccade slope, histogram of saccade length, histogram of saccade duration, histogram of saccade velocity, histogram of fixation duration, fixation histogram, top-ten salient coordinates, and saliency map. We utilize machine learning approach to analyze the performance of features by learning a support vector machine and exploiting various feature fusion schemes. The experiments reveal that 'saliency map', 'fixation histogram', 'histogram of fixation duration', and 'histogram of saccade slope' are the most contributing features. The selected features signify the influence of fixation information and angular behavior of eye movements in the recognition of the valence of images.

Chemometric assisted ultrasound leaching-solid phase extraction followed by dispersive-solidification liquid-liquid microextraction for determination of organophosphorus pesticides in soil samples.

Ultrasound leaching-solid phase extraction (USL-SPE) followed by dispersive-solidification liquid-liquid microextraction (DSLLME) was developed for preconcentration and determination of organophosphorus pesticides (OPPs) in soil samples prior gas chromatography-mass spectrometry analysis. At first, OPPs were ultrasonically leached from soil samples by using methanol. After centrifugation, the separated methanol was diluted to 50 mL with double-distillated water and passed through the C18 SPE cartridge. OPPs were eluted with 1 mL acetonitrile. Thus, 1 mL acetonitrile extract (disperser solvent) and 10 µL 1-undecanol (extraction solvent) were added to 5 mL double-distilled water and a DSLLME technique was applied. The variables of interest in the USL-SPE-DSLLME method were optimized with the aid of chemometric approaches. First, in screening experiments, fractional factorial design (FFD) was used for selecting the variables which significantly affected the extraction procedure. Afterwards, the significant variables were optimized using response surface methodology (RSM) based on central composite design (CCD). Under the optimum conditions, the enrichment factors were 6890-8830. The linear range was 0.025-625 ng g(-1) and limits of detection (LODs) were between 0.012 and 0.2 ng g(-1). The relative standard deviations (RSDs) were in the range of 4.06-8.9% (n=6). The relative recoveries of OPPs from different soil samples were 85-98%.

Response surface methodology based on central composite design as a chemometric tool for optimization of dispersive-solidification liquid-liquid microextraction for speciation of inorganic arsenic in environmental water samples.

Dispersive-solidification liquid-liquid microextraction (DSLLME) coupled with electrothermal atomic absorption spectrometry (ETAAS) was developed for preconcentration and determination of inorganic arsenic (III, V) in water samples. At pH=1, As(III) formed complex with ammonium pyrrolidine dithiocarbamate (APDC) and extracted into the fine droplets of 1-dodecanol (extraction solvent) which were dispersed with ethanol (disperser solvent) into the water sample solution. After extraction, the organic phase was separated by centrifugation, and was solidified by transferring into an ice bath. The solidified solvent was transferred to a conical vial and melted quickly at room temperature. As(III) was determined in the melted organic phase while As(V) remained in the aqueous layer. Total inorganic As was determined after the reduction of the pentavalent forms of arsenic with sodium thiosulphate and potassium iodide. As(V) was calculated by difference between the concentration of total inorganic As and As(III). The variable of interest in the DSLLME method, such as the volume of extraction solvent and disperser solvent, pH, concentration of APDC (chelating agent), extraction time and salt effect, was optimized with the aid of chemometric approaches. First, in screening experiments, fractional factorial design (FFD) was used for selecting the variables which significantly affected the extraction procedure. Afterwards, the significant variables were optimized using response surface methodology (RSM) based on central composite design (CCD). In the optimum conditions, the proposed method has been successfully applied to the determination of inorganic arsenic in different environmental water samples and certified reference material (NIST RSM 1643e).

Comparison of ultrasound-assisted emulsification and dispersive liquid-liquid microextraction methods for the speciation of inorganic selenium in environmental water samples using low density extraction solvents.

Herein, ultrasound-assisted emulsification microextraction (USAEME) and dispersive liquid-liquid microextraction (DLLME) methods based on applying low-density organic solvents have been critically compared for the speciation of inorganic selenium, Se(IV) (selenite) and Se(VI) (selenate) in environmental water samples by gas chromatography-flame ionization detection (GC-FID). At pH 2 and T=75°C for 7 min, only Se(IV) was able to form the piazselenol complex with 4-nitro-o-phenylenediamine. Piazselenol was extracted using an extraction solvent and was injected into a GC-FID instrument for the determination of Se(IV). Conveniently, Se(VI) remained in the aqueous phase. Total inorganic selenium was determined after the reduction of Se(VI) to Se(IV) and prior to the above procedures. The Se(VI) concentration was calculated as the difference between the measured total inorganic selenium and Se(IV) content. The effect of various experimental parameters on the efficiencies of the two methods and their optimum values were studied with the aid of response surface methodology and experimental design. Under the optimal conditions, the limit of detections (LODs) for Se(IV) obtained by USAEME-GC-FID and DLLME-GC-FID were 0.05 and 0.11 ng mL(-1), respectively. The relative standard deviations (RSDs, n=6) for the measurement 10 ng mL(-1) of Se(IV) were 5.32% and 4.57% with the enrichment factors of 2491 and 1129 for USAEME-GC-FID and DLLME-GC-FID, respectively. Both methods were successfully applied to the analysis of inorganic selenium in different environmental water samples and certified reference material (NIST SRM 1643e).

Speciation and determination of ultra trace amounts of inorganic tellurium in environmental water samples by dispersive liquid-liquid microextraction and electrothermal atomic absorption spectrometry.

A simple and powerful method has been developed for the rapid and selective determination of Te(IV) and Te(VI), employing dispersive liquid-liquid microextraction combined with electrothermal atomic absorption spectrometry using palladium as permanent modifier. Under acidic conditions pH 1, only Te(IV) can form a complex with ammonium pyrrolidine dithiocarbamate (APDC) and therefore be extracted into fine droplets of carbon tetrachloride (extraction solvent) which are dispersed with ethanol into the water sample solution. After centrifugation, Te(IV) was determined in the sedimented organic phase while Te(VI) remained in the aqueous phase. Total inorganic tellurium was determined after the reduction of the Te(VI) to Te(IV). Te(VI) was calculated as the difference between the measured total inorganic tellurium and Te(IV) content. The effective parameters for improving the efficiency of microextraction process were investigated by using experimental and central composite designs. Under optimal conditions the enrichment factor was 125 and the calibration graph was linear in the range of 0.015-1 ng mL(-1) with detection limit and characteristic mass of 0.004 ng mL(-1) and 0.033 pg, respectively. The relative standard deviation for 0.5 ng mL(-1) of tellurium measurement was 3.6% (n=6) at ash and atomization temperature, 900 and 2600 degrees C, respectively. The recoveries of spiked Te(IV) and Te(VI) to the environmental water samples were 89.6-101.3% and 96.6-99.1%, respectively. The accuracy is also evaluated by applying the proposed method to certified reference material (NIST SRM 1643e), for which the result was in a good agreement with the certified values reported for this CRM (95% confidence level).