Multianalyte biosensors have been of interest in various applications, especially in healthcare areas that target a broad range of biomarkers related to various pathological diseases. However, successful examples of such sensors generally utilize electrochemical transducers, a fact that limits their use as implants due to the presence of interferents in vivo, the difficulty of transdermal signal transduction, and the difficulty of miniaturizing the electronics into an integrated biocompatible form factor suitable for implantation. In this study, we demonstrate an attractive alternative for multiplexed sensing platform based on oxidoreductase enzymes coupled with optically distinct oxygen-sensitive metalloporphyrin phosphors, which are immobilized within nanofilm-coated alginate microparticles; these are embedded in discrete compartments of a single miniature biocompatible hydrogel to achieve a "barcode" sensor device. Continuous multiplex oxygen and glucose monitoring were demonstrated through the measurement of phosphorescence lifetime changes of the metalloporphyrin phosphors when exposed to different environmental conditions. The phosphorescence lifetime exhibited a negative correlation with increases in oxygen concentration for all compartments. In contrast, the oxygen-responsive assays maintained a constant phosphorescence lifetime and the glucose-responsive assays showed increased phosphorescence lifetime when the glucose concentration increased from 0 to 400 mg/dL. This observation confirmed the desired behavior without any apparent crosstalk between the adjacent oxygen- and glucose-responsive compartments. Furthermore, the sensors demonstrated high stability during repeated glucose challenges over ten cycles. These findings suggest that the hydrogel barcode optical sensing platform has the potential for use in various situations requiring multiplexed chemical analysis such as in continuous medical monitoring.
The coronavirus disease (COVID-19) pandemic has increased pressure to develop low-cost, compact, user-friendly, and ubiquitous virus sensors for monitoring infection outbreaks in communities and preventing economic damage resulting from city lockdowns. As proof of concept, we developed a wearable paper-based virus sensor based on a molecular imprinting technique, using a conductive polyaniline (PANI) polymer to detect the lentivirus as a test sample. This sensor detected the lentivirus with a 4181 TU/mL detection limit in liquid and 0.33% to 2.90% detection efficiency in aerosols at distances ranging from 30 cm to 60 cm. For fabrication, a mixture of a PANI monomer solution and virus were polymerized together to form a conductive PANI sensing element on a polyethylene terephthalate (PET) paper substrate. The sensing element exhibited formation of virus recognition sites after the removal of the virus via ultrasound sonication. A dry measurement technique was established that showed aerosol virus detection by the molecularly imprinted sensors within 1.5 h of virus spraying. This was based on the mechanism via which dispensing virus droplets on the PANI sensing element induced hybridization of the virus and molecularly imprinted virus recognition templates in PANI, influencing the conductivity of the PANI film upon drying. Interestingly, the paper-based virus sensor was easily integrated with a wearable face mask for the detection of viruses in aerosols. Since the paper sensor with molecular imprinting of virus recognition sites showed excellent stability in dry conditions for long periods of time, unlike biological reagents, this wearable biosensor will offer an alternative approach to monitoring virus infections in communities.
Methylmalonic acid (MMA) plays a vital role in metabolism and energy production. It has been studied and reported as a sensitive early indicator for mild or serious Vitamin B12 deficiency. The normal range in health people is from 0.00 to 0.40 µM. Thus, most of MMA detection research was focused on Vitamin B12 deficiency with a small detection range. Recently, MMA has been reported to promote tumor progression due to age-induced accumulation. It was found that MMA concentration can reach as high as 80 µM in elderly people. MMA can be of great value as a promising biomarker for cancer diagnostics, as well as a therapeutic target for cancer treatment. Clinical determination of MMA concentration is by the method of gas chromatography mass spectroscopy (GCMS) or liquid chromatography mass spectroscopy (LCMS). However, these methods require extensive sample pre-treatment and large sample volume. They are also expensive and time-consuming. Hence, we proposed an attractive and effective strategy to detect MMA with a broad linear range by a low-cost molecularly imprinted polyaniline paper sensor. The polyaniline paper strip was fabricated by a one-step solution process using MMA as the template by molecular imprinting technology. The concentration of MMA was determined by the resistance change of the paper sensor. A calibration curve as a function of MMA concentration in aqueous solution was acquired with a correlation coefficient of 0.962. We demonstrated detection of the added MMA in plasma with a wide concentration range of 0 to 100 µM with a limit of detection (LoD) of 0.197 µM. This low-cost disposable paper sensor shows great potential in point-of-care MMA detection for cancer prognostics and diagnostics, especially in underserved communities.
Perfluorinated compounds like perfluorooctanesulfonic acid (PFOS) are synthetic water pollutants and have accumulated in environments for decades, causing a serious global health issue. Conventional assays rely on liquid chromatography and mass spectroscopy that are very expensive and complicated and thus limit the large-scale monitoring of PFOS in wastewater. To achieve low-cost and accurate detection of PFOS, we designed a paper-based sensor with molecularly imprinted polyaniline electrodes that have recognition sites specific to PFOS. The calibration curve of resistivity ratios as a function of PFOS concentrations has a linear range from 1 to 100 ppt with a coefficient of determination of 0.995. The estimated limit of detection is 1.02 ppt. We also investigated attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS) spectra of the surface of the polyaniline (PANI) electrodes to propose the potential recognition sites in polyaniline matrix and the detection mechanism. This electrical paper sensor with low cost and excellent sensitivity and selectivity provides the potential for large-scale monitoring of wastewater.
Extracellular vesicles (EVs) play an important role in intercellular communication. Recently, there has been increasing interest in EVs as potential diagnostic biomarkers and therapeutic vehicles. However, the molecular properties and cargo information of EV subpopulations have not yet been fully investigated due to lack of reliable and reproducible EV separation technology. Current approaches have faced difficulties with efficiently isolating EVs from biofluids, especially subpopulations of small EVs. Here, we report an EV isolation method based on a size-selective microfluidic platform (ExoSMP) via nanomembrane filtration and electrophoretic force. This unique platform offers an enhanced approach to sorting a heterogeneous population of EVs based on size, with the additional advantages of being label-free and low-cost, and featuring a short processing time (<1 h), and convenient integration with downstream analysis. In this research, we used ExoSMP to demonstrate the isolation of cancer-derived small EVs (30-120 nm) with high recovery (94.2%) and reproducibility at an optimum sample flow rate. Furthermore, we investigated isolation of EV subpopulations by altering nanomembrane combinations with different pore size combinations (50 and 100 nm, 30 and 100 nm, 30 and 200 nm, and 30 and 50 nm). This ExoSMP technique can serve as a standardized EV isolation/separation tool, facilitating the clinical prospects of EVs and opening up a new avenue for future point-of-care applications in liquid biopsies.
A low-cost and enzyme-free glucose paper sensor is presented as a promising alternative to glucose test strips. This paper-based glucose sensor is prepared with molecularly imprinted (MIP) polyaniline (PANI) electrode. The determination of glucose concentrations was studied by the impedance change of the paper sensor before and after the blood samples dispensing at a low frequency. A comparison of the linear and polynomial regression was applied to analyze the impedance ratio as a function of glucose concentrations. The proposed glucose paper sensor showed a limit of detection (LoD) of 1.135 mM. This novel and non-enzymatic paper sensor suggests a low-cost glucose test assay and can improve the quality of routine testing for diabetic patients.
In this work, we present a portable low-cost point-of-care (POC) blood glucose monitoring system, which is composed of an additively manufactured smartphone-based optical detection platform and a disposable paper based glucose colorimetric detection device. To improve the uniformity of color development and manufacture efficiency, the disposable micro paper-based device (mu PAD) was functionalized and mass-produced by inkjet printing of colorimetric assay 3,3 ',5,5 '-Tetramethylbenzidine (TMB) substrate and glucose oxidase/horseradish peroxidase (GOx/HRP) bi-enzymatic system on the sensing zone. The separation of plasma from blood was achieved by the membrane filter laminated on the top of the sensing zone. A 3D printed smartphone-based optical detection platform enables the facile readout and analysis of glucose detection by avoiding the influence of intensity from the variation of ambient light. This POC system has been demonstrated to successfully determine a wide range of blood glucose (0.5-2.84 mg/ml) with limit of detection as 5 mg/dl (0.28 mM). The detection of blood glucose directly from human whole blood samples was performed. Our results showed relative errors ranging from 4.37% to 14.41% compared with a spectrophotometry method, and 3.83%-14.53% compared with a commercial glucose meter. With a combination of advantages of low-cost, high reliability and high fabrication efficiency, this system has the great potential to be a competitive method for POC glucose monitoring, especially for patients in underserved communities.
For the hundreds of millions of worldwide diabetic patients, glucose test strips are the most important and commonly used tool for monitoring blood glucose levels. Commercial test strips use glucose oxidases as recognition agents, which increases the cost and reduces the durability of test strips. To lower the cost of glucose sensors, we developed a paper-based electrical sensor with molecularly imprinted glucose recognition sites and demonstrated the determination of various glucose concentrations in bovine blood solutions. The sensing electrode is integrated with molecular recognition sites in the conductive polymer. A calibration graph as a function of glucose concentration in aqueous solution was acquired and matched with a correlation coefficient of 0.989. We also demonstrated the determination of the added glucose concentrations ranging from 2.2 to 11.1 mM in bovine blood samples with a linear correlation coefficient of 0.984. This non-enzymatic glucose sensor has the potential to reduce the health care cost of test strips as well as make glucose sensor test strips more accessible to underserved communities.
Exosomes are nanosized extracellular vesicles that play a significant role in cell-cell communication. Recently, there is significant interest in exosome-related fundamental research, especially subgroups of exosomes as potential biomarkers for cancer diagnosis and prognosis. In this paper, we report a new size selective isolation method via elastic lift force and nanomembrane filtration and demonstrated the liposome recovery rate of 92.5% from a mixture solution of 1 μm polystyrene beads, 100 nm liposomes and proteins as a proof of concept for exosome isolation. This single microfluidic platform offers an improved approach with short processing time (<; 2 hours) and low cost, and shows potential broad applicability to cancer biomarker studies.
Per- and poly-fluoroalkyl substances (PFASs) are man-made chemicals that are toxic and widely detected in the environment, including drinking water sources. A cost-effective treatment process for PFASs is currently not available. We developed reusable hydrogel sorbents to remove long- and short-chain perfluoroalkyl acids and 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoic acid (GenX), which is are emerging PFAS. Through fluoridation and amination of poly(ethylene glycol) diacrylate (PEGDA), the newly synthesized sorbents can sorb the five targeted PFASs (perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorobutanesulfonic acid (PFBS), and perfluorobutanoic acid (PFBA) and GenX) to different degrees from aqueous solution. Aminated PEGDA showed the highest sorption capacity for all five PFASs, particularly for PFBA and PFBS. The bifunctionalized PEGDA showed higher capacities for PFOA and PFOS, suggesting that both hydrophobic interactions and charges contribute to the sorption. Both aminated and bifunctionalized sorbents can remove GenX from water, with the highest sorption capacity of 98.7 μmol g aminated PEGDA-1 within 6 h. The absorbed PFASs on the sorbents were observed and characterized by Fourier-transform infrared spectroscopy. The spent sorbents were reusable after readily regenerated with 70% methanol contained 1% NaCl.
Amorphous indium tin oxide (a-ITO) thin-film transistors (TFTs) were fabricated with the channel layer deposited by the cosputtering of In2O3 and SnO2 ceramic targets. It is shown that the cosputter-deposited ITO film for the channel layer well keeps in the amorphous structure even after being annealed at 300 degrees if the sputtering powers of the two targets are properly selected. The fabricated a-ITO TFTs in the cosputtering technique show a high device performance, including a field-effect mobility of 25.9 cm(2)V(-1)s(-1), a subthreshold swing of 0.33 V/decade, an ON/OFF-current ratio of >1 x 10(9), and a desirable threshold voltage variation range. In addition, an acceptable characteristic stability under electrical stress is also observed in the passivated and annealed a-ITO TFTs.
The impacts of substrate heating scheme on the characteristics of amorphous indium-gallium-zinc-oxide (a-IGZO) TFTs fabricated on flexible PEN substrate are investigated. For the a-IGZO TFTs fabrication, the substrate is heated during the a-IGZO deposition, pre-annealing in N2 is also conducted before passivation layer deposition, and post-annealing is done at last. The results show that the pre-annealing and post-annealing improve the hysteresis characteristics, but degrade the field-effect mobility μFE and subthreshold swing SS. In contrast, both the hysteresis voltage Vh and the electrical performance are enhanced when the a-IGZO is sputtered with substrate temperature of 150°C. The major performance parameters μFE, SS, and Vh are 7.34 cm2/Vs, 0.438 V/dec, and 2.3 V, respectively.
P-type copper-based oxide thin films are fabricated by DC reactive sputtering of copper at room temperature (RT) and studied as a function of oxygen partial pressure (OPP). Cu2O crystalline phase is observed at 10% OPP and it changes to CuO when OPP increases to 15%. The crystallinity of the deposited films decreases sharply when OPP increases to ≥20%. The p-type conductivity of the deposited films is identified by Hall measurements. Both the as-deposited and post-annealed bottom gate TFTs using CuO as active layers show significant field effect. The post-annealed CuO TFT with 30% OPP has the p-type characteristics with μFE ≈ 5 × 10-3 cm-2/V·s, and an on/off ratio around 102.