Homocysteine Solution-Induced Response in Aerosol Jet Printed OECTs by Means of Gold and Platinum Gate Electrodes

Homocysteine (Hcy) is a non-protein, sulfur-containing amino acid, which is recognized as a possible risk factor for coronary artery and other pathologies when its levels in the blood exceed the normal range of between 5 and 12 μmol/L (hyperhomocysteinemia). At present, standard procedures in laboratory medicine, such as high-performance liquid chromatography (HPLC), are commonly employed for the quantitation of total Hcy (tHcy), i.e., the sum of the protein-bound (oxidized) and free (homocystine plus reduced Hcy) forms, in biological fluids (particularly, serum or plasma). Here, the response of Aerosol Jet-printed organic electrochemical transistors (OECTs), in the presence of either reduced (free) and oxidized Hcy-based solutions, was analyzed. Two different experimental protocols were followed to this end: the former consisting of gold (Au) electrodes’ biothiol-induced thiolation, while the latter simply used bare platinum (Pt) electrodes. Electrochemical impedance spectroscopy (EIS) analysis was performed both to validate the gold thiolation protocol and to gain insights into the reduced Hcy sensing mechanism by the Au-gated OECTs, which provided a final limit of detection (LoD) of 80 nM. For the OECT response based on Platinum gate electrodes, on the other hand, a LoD of 180 nM was found in the presence of albumin-bound Hcy, with this being the most abundant oxidized Hcy-form (i.e., the protein-bound form) in physiological fluids. Despite the lack of any biochemical functionalization supporting the response selectivity, the findings discussed in this work highlight the potential role of OECT in the development of low-cost point-of-care (POC) electronic platforms that are suitable for the evaluation, in humans, of Hcy levels within the physiological range and in cases of hyperhomocysteinemia.

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Quantitative Clinical Diagnostic Analysis of Acetone in Human Blood by HPLC: A Metabolomic Search for Acetone as Indicator

Journal of Analytical Methods in Chemistry ◽

10.1155/2016/5176320 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7

Author(s):

Esin Akgul Kalkan ◽

Mehtap Sahiner ◽

Dilek Ulker Cakir ◽

Duygu Alpaslan ◽

Selehattin Yilmaz

Keyword(s):

Human Blood ◽

High Performance ◽

Limit Of Detection ◽

Biological Fluids ◽

Low Cost ◽

Calibration Graph ◽

Array Detector ◽

Diagnostic Analysis ◽

Clinical Diagnostic ◽

Accuracy And Precision

Using high-performance liquid chromatography (HPLC) and 2,4-dinitrophenylhydrazine (2,4-DNPH) as a derivatizing reagent, an analytical method was developed for the quantitative determination of acetone in human blood. The determination was carried out at 365 nm using an ultraviolet-visible (UV-Vis) diode array detector (DAD). For acetone as its 2,4-dinitrophenylhydrazone derivative, a good separation was achieved with a ThermoAcclaim C18column (15 cm×4.6 mm×3 μm) at retention time (tR) 12.10 min and flowrate of 1 mL min−1using a (methanol/acetonitrile) water elution gradient. The methodology is simple, rapid, sensitive, and of low cost, exhibits good reproducibility, and allows the analysis of acetone in biological fluids. A calibration curve was obtained for acetone using its standard solutions in acetonitrile. Quantitative analysis of acetone in human blood was successfully carried out using this calibration graph. The applied method was validated in parameters of linearity, limit of detection and quantification, accuracy, and precision. We also present acetone as a useful tool for the HPLC-based metabolomic investigation of endogenous metabolism and quantitative clinical diagnostic analysis.

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Label free, electric field mediated ultrasensitive electrochemical point-of-care device for CEA detection

Scientific Reports ◽

10.1038/s41598-021-82580-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

B. Chakraborty ◽

A. Das ◽

N. Mandal ◽

N. Samanta ◽

N. Das ◽

...

Keyword(s):

Electric Field ◽

Electrochemical Impedance ◽

Limit Of Detection ◽

Point Of Care ◽

Low Cost ◽

Zno Nanorods ◽

Hybrid Nanostructures ◽

Electrochemical Sensing ◽

Label Free ◽

Electron Transfer Rate

AbstractDeveloping point-of-care (PoC) diagnostic platforms for carcinoembryonic antigen detection is essential. However, thefew implementations of transferring the signal amplification strategies in electrochemical sensing on paper-based platforms are not satisfactory in terms of detection limit (LOD). In the quest for pushing down LOD, majority of the research has been targeted towards development of improved nanostructured substrates for entrapping more analyte molecules and augmenting the electron transfer rate to the working electrode. But, such approaches have reached saturation. This paper focuses on enhancing the mass transport of the analyte towards the sensor surface through the application of an electric field, in graphene-ZnO nanorods heterostructure. These hybrid nanostructures have been deposited on flexible polyethylene terephthalate substrates with screen printed electrodes for PoC application. The ZnO nanorods have been functionalized with aptamers and the working sensor has been integrated with smartphone interfaced indigenously developed low cost potentiostat. The performance of the system, requiring only 50 µl analyte has been evaluated using electrochemical impedance spectroscopy and validated against commercially available ELISA kit. Limit of detection of 1 fg/ml in human serum with 6.5% coefficient of variation has been demonstrated, which is more than three orders of magnitude lower than the existing attempts on PoC device.

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A Graphene-PEDOT:PSS Modified Paper-Based Aptasensor for Electrochemical Impedance Spectroscopy Detection of Tumor Marker

Sensors ◽

10.3390/s20051372 ◽

2020 ◽

Vol 20 (5) ◽

pp. 1372 ◽

Cited By ~ 4

Author(s):

Yi-Kuang Yen ◽

Chen-Hsiang Chao ◽

Ya-Shin Yeh

Keyword(s):

Electrochemical Impedance Spectroscopy ◽

Impedance Spectroscopy ◽

Electrochemical Impedance ◽

Limit Of Detection ◽

Point Of Care ◽

Low Cost ◽

Serum Samples ◽

Analytical Instruments ◽

Buffer Solutions ◽

Early Cancer Diagnosis

A graphene and poly (3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) modified conductive paper-based electrochemical impedance spectroscopy (EIS) aptasensor has been successfully fabricated by a simple and continuous coating process. A graphene/PEDOT:PSS modified paper electrode forms the nanocomposite providing a conductive and sensitive substrate for further aptamer functionalization of the biosensor. This low-cost paper-based aptasensor exhibits its sensitivity to carcinoembryonic antigens (CEA) in standard buffer solutions and human serum samples in a linear range of 0.77–14 ng·mL−1. The limit of detection (LOD) is found to be 0.45 ng·mL−1 and 1.06 ng·mL−1 for CEA in both samples, separately. This aptamer-based sensing device was also evaluated and received a good correlation with the immunoassay detection method. The proposed paper-based aptasensor has demonstrated its potential as a rapid simple point-of-care analytical platform for early cancer diagnosis in less developed areas where manufacturing facilities, analytical instruments, and trained specialists are limited.

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Rapid and Sensitive Detection of miRNA Based on AC Electrokinetic Capacitive Sensing for Point-of-Care Applications

Sensors ◽

10.3390/s21123985 ◽

2021 ◽

Vol 21 (12) ◽

pp. 3985

Author(s):

Nan Wan ◽

Yu Jiang ◽

Jiamei Huang ◽

Rania Oueslati ◽

Shigetoshi Eda ◽

...

Keyword(s):

Limit Of Detection ◽

Point Of Care ◽

Low Cost ◽

Clinical Diagnostics ◽

Detection Methods ◽

Capacitive Sensing ◽

Application Potential ◽

Mirna Detection ◽

Mirna 25 ◽

Low Sensitivity

A sensitive and efficient method for microRNAs (miRNAs) detection is strongly desired by clinicians and, in recent years, the search for such a method has drawn much attention. There has been significant interest in using miRNA as biomarkers for multiple diseases and conditions in clinical diagnostics. Presently, most miRNA detection methods suffer from drawbacks, e.g., low sensitivity, long assay time, expensive equipment, trained personnel, or unsuitability for point-of-care. New methodologies are needed to overcome these limitations to allow rapid, sensitive, low-cost, easy-to-use, and portable methods for miRNA detection at the point of care. In this work, to overcome these shortcomings, we integrated capacitive sensing and alternating current electrokinetic effects to detect specific miRNA-16b molecules, as a model, with the limit of detection reaching 1.0 femto molar (fM) levels. The specificity of the sensor was verified by testing miRNA-25, which has the same length as miRNA-16b. The sensor we developed demonstrated significant improvements in sensitivity, response time and cost over other miRNA detection methods, and has application potential at point-of-care.

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Demonstration of a Label-Free and Low-Cost Optical Cavity-Based Biosensor Using Streptavidin and C-Reactive Protein

Biosensors ◽

10.3390/bios11010004 ◽

2020 ◽

Vol 11 (1) ◽

pp. 4

Author(s):

Donggee Rho ◽

Seunghyun Kim

Keyword(s):

Limit Of Detection ◽

Point Of Care ◽

Low Cost ◽

Optical Cavity ◽

Sample Volume ◽

Small Sample ◽

Label Free ◽

C Reactive Protein ◽

Reactive Protein ◽

Cavity Structure

An optical cavity-based biosensor (OCB) has been developed for point-of-care (POC) applications. This label-free biosensor employs low-cost components and simple fabrication processes to lower the overall cost while achieving high sensitivity using a differential detection method. To experimentally demonstrate its limit of detection (LOD), we conducted biosensing experiments with streptavidin and C-reactive protein (CRP). The optical cavity structure was optimized further for better sensitivity and easier fluid control. We utilized the polymer swelling property to fine-tune the optical cavity width, which significantly improved the success rate to produce measurable samples. Four different concentrations of streptavidin were tested in triplicate, and the LOD of the OCB was determined to be 1.35 nM. The OCB also successfully detected three different concentrations of human CRP using biotinylated CRP antibody. The LOD for CRP detection was 377 pM. All measurements were done using a small sample volume of 15 µL within 30 min. By reducing the sensing area, improving the functionalization and passivation processes, and increasing the sample volume, the LOD of the OCB are estimated to be reduced further to the femto-molar range. Overall, the demonstrated capability of the OCB in the present work shows great potential to be used as a promising POC biosensor.

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Pocket MUSE: an affordable, versatile and high-performance fluorescence microscope using a smartphone

Communications Biology ◽

10.1038/s42003-021-01860-5 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Yehe Liu ◽

Andrew M. Rollins ◽

Richard M. Levenson ◽

Farzad Fereidouni ◽

Michael W. Jenkins

Keyword(s):

High Performance ◽

Point Of Care ◽

Low Cost ◽

Consumer Electronics ◽

Practical Implementation ◽

The Novel ◽

Point Of Care Diagnostics ◽

Optical Module ◽

Optical Configuration ◽

User Friendly

AbstractSmartphone microscopes can be useful tools for a broad range of imaging applications. This manuscript demonstrates the first practical implementation of Microscopy with Ultraviolet Surface Excitation (MUSE) in a compact smartphone microscope called Pocket MUSE, resulting in a remarkably effective design. Fabricated with parts from consumer electronics that are readily available at low cost, the small optical module attaches directly over the rear lens in a smartphone. It enables high-quality multichannel fluorescence microscopy with submicron resolution over a 10× equivalent field of view. In addition to the novel optical configuration, Pocket MUSE is compatible with a series of simple, portable, and user-friendly sample preparation strategies that can be directly implemented for various microscopy applications for point-of-care diagnostics, at-home health monitoring, plant biology, STEM education, environmental studies, etc.

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Integrating high-performing electrochemical transducers in lateral flow assay

Analytical and Bioanalytical Chemistry ◽

10.1007/s00216-021-03301-y ◽

2021 ◽

Author(s):

Antonia Perju ◽

Nongnoot Wongkaew

Keyword(s):

High Performance ◽

Point Of Care ◽

Low Cost ◽

High Sensitivity ◽

Lateral Flow ◽

Analytical Performance ◽

Label Free ◽

High Performing ◽

Lateral Flow Assays ◽

Electrochemical Transducers

AbstractLateral flow assays (LFAs) are the best-performing and best-known point-of-care tests worldwide. Over the last decade, they have experienced an increasing interest by researchers towards improving their analytical performance while maintaining their robust assay platform. Commercially, visual and optical detection strategies dominate, but it is especially the research on integrating electrochemical (EC) approaches that may have a chance to significantly improve an LFA’s performance that is needed in order to detect analytes reliably at lower concentrations than currently possible. In fact, EC-LFAs offer advantages in terms of quantitative determination, low-cost, high sensitivity, and even simple, label-free strategies. Here, the various configurations of EC-LFAs published are summarized and critically evaluated. In short, most of them rely on applying conventional transducers, e.g., screen-printed electrode, to ensure reliability of the assay, and additional advances are afforded by the beneficial features of nanomaterials. It is predicted that these will be further implemented in EC-LFAs as high-performance transducers. Considering the low cost of point-of-care devices, it becomes even more important to also identify strategies that efficiently integrate nanomaterials into EC-LFAs in a high-throughput manner while maintaining their favorable analytical performance.

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Determination of amino acids in human biological fluids by high-performance liquid chromatography: critical review

Amino Acids ◽

10.1007/s00726-021-03002-x ◽

2021 ◽

Author(s):

Grażyna Gałęzowska ◽

Joanna Ratajczyk ◽

Lidia Wolska

Keyword(s):

Amino Acids ◽

Amino Acid ◽

High Performance ◽

Hplc Analysis ◽

Limit Of Detection ◽

Biological Fluids ◽

Analytical Techniques ◽

Epidemiological Studies ◽

Preparation Conditions

AbstractThe quantitation and qualification of amino acids are most commonly used in clinical and epidemiological studies, and provide an excellent way of monitoring compounds in human fluids which have not been monitored previously, to prevent some diseases. Because of this, it is not surprising that scientific interest in evaluating these compounds has resurfaced in recent years and has precipitated the development of a multitude of new analytical techniques. This review considers recent developments in HPLC analytics on the basis of publications from the last few years. It helps to update and systematize knowledge in this area. Particular attention is paid to the progress of analytical methods, pointing out the advantages and drawbacks of the various techniques used for the preparation, separation and determination of amino acids. Depending on the type of sample, the preparation conditions for HPLC analysis change. For this reason, the review has focused on three types of samples, namely urine, blood and cerebrospinal fluid. Despite time-consuming sample preparation before HPLC analysis, an additional derivatization technique should be used, depending on the detection technique used. There are proposals for columns that are specially modified for amino acid separation without derivatization, but the limit of detection of the substance is less beneficial. In view of the fact that amino acid analyses have been performed for years and new solutions may generate increased costs, it may turn out that older proposals are much more advantageous.

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A haemagglutination test for rapid detection of antibodies to SARS-CoV-2

10.1101/2020.10.02.20205831 ◽

2020 ◽

Author(s):

Alain Townsend ◽

Pramila Rijal ◽

Julie Xiao ◽

Tiong Kit Tan ◽

Kuan-Ying A Huang ◽

...

Keyword(s):

High Performance ◽

Point Of Care ◽

Low Cost ◽

Glycophorin A ◽

Red Cell ◽

Special Equipment ◽

Cell Agglutination ◽

Haemagglutination Test ◽

Point Of Care Test ◽

Laboratory Facilities

ABSTRACTSerological detection of antibodies to SARS-CoV-2 is essential for establishing rates of seroconversion in populations, detection of seroconversion after vaccination, and for seeking evidence for a level of antibody that may be protective against COVID-19 disease. Several high-performance commercial tests have been described, but these require centralised laboratory facilities that are comparatively expensive, and therefore not available universally. Red cell agglutination tests have a long history in blood typing, and general serology through linkage of reporter molecules to the red cell surface. They do not require special equipment, are read by eye, have short development times, low cost and can be applied as a Point of Care Test (POCT). We describe a red cell agglutination test for the detection of antibodies to the SARS-CoV-2 receptor binding domain (RBD). We show that the Haemagglutination Test (“HAT”) has a sensitivity of 90% and specificity of 99% for detection of antibodies after a PCR diagnosed infection. The HAT can be titrated, detects rising titres in the first five days of hospital admission, correlates well with a commercial test that detects antibodies to the RBD, and can be applied as a point of care test. The developing reagent is composed of a previously described nanobody to a conserved glycophorin A epitope on red cells, linked to the RBD from SARS-CoV-2. It can be lyophilised for ease of shipping. We have scaled up production of this reagent to one gram, which is sufficient for ten million tests, at a cost of ∼0.27 UK pence per test well. Aliquots of this reagent are ready to be supplied to qualified groups anywhere in the world that need to detect antibodies to SARS-CoV-2, but do not have the facilities for high throughput commercial tests.

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A Facile Fabrication of a Potentiometric Arrayed Glucose Biosensor Based on Nafion-GOx/GO/AZO

Sensors ◽

10.3390/s20040964 ◽

2020 ◽

Vol 20 (4) ◽

pp. 964

Author(s):

Jung-Chuan Chou ◽

Si-Hong Lin ◽

Tsu-Yang Lai ◽

Po-Yu Kuo ◽

Chih-Hsien Lai ◽

...

Keyword(s):

Zinc Oxide ◽

Electrochemical Impedance ◽

Limit Of Detection ◽

Low Cost ◽

Glucose Biosensor ◽

Average Sensitivity ◽

Glucose Biosensors ◽

Coating Method ◽

Aluminum Doped Zinc Oxide ◽

Screen Printing Technology

In this study, the potentiometric arrayed glucose biosensors, which were based on zinc oxide (ZnO) or aluminum-doped zinc oxide (AZO) sensing membranes, were fabricated by using screen-printing technology and a sputtering system, and graphene oxide (GO) and Nafion-glucose oxidase (GOx) were used to modify sensing membranes by using the drop-coating method. Next, the material properties were characterized by using a Raman spectrometer, a field-emission scanning electron microscope (FE-SEM), and a scanning probe microscope (SPM). The sensing characteristics of the glucose biosensors were measured by using the voltage–time (V-T) measurement system. Finally, electrochemical impedance spectroscopy (EIS) was conducted to analyze their charge transfer abilities. The results indicated that the average sensitivity of the glucose biosensor based on Nafion-GOx/GO/AZO was apparently higher than that of the glucose biosensor based on Nafion-GOx/GO/ZnO. In addition, the glucose biosensor based on Nafion-GOx/GO/AZO exhibited an excellent average sensitivity of 15.44 mV/mM and linearity of 0.997 over a narrow range of glucose concentration range, a response time of 26 s, a limit of detection (LOD) of 1.89 mM, and good reproducibility. In terms of the reversibility and stability, the hysteresis voltages (VH) were 3.96 mV and 2.42 mV. Additionally, the glucose biosensor also showed good anti-inference ability and reproducibility. According to these results, it is demonstrated that AZO is a promising material, which could be used to develop a reliable, simple, and low-cost potentiometric glucose biosensor.

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