This paper describes for the first time the fabrication of pencil drawn electrodes (PDE) on paper platforms for capacitively coupled contactless conductivity detection (C4D) on electrophoresis ...microchips. PDE‐C4D devices were attached on PMMA electrophoresis chips and used for detection of K+ and Na+ in human tear samples. PDE‐C4D devices were produced on office paper and chromatographic paper platforms and their performance were thoroughly investigated using a model mixture containing K+, Na+, and Li+. In comparison with chromatographic paper, PDE‐C4D fabricated on office paper has exhibited better performance due to its higher electrical conductivity. Furthermore, the detector response was similar to that recorded with electrodes prepared with copper adhesive tape. The fabrication of PDE‐C4D on office paper has offered great advantages including extremely low cost (< $ 0.004 per unit), reduced fabrication time (< 5 min), and minimal instrumentation (pencil and paper). The proposed electrodes demonstrated excellent analytical performance with good reproducibility. For an inter‐PDE comparison (n = 7), the RSD values for migration time, peak area, and separation efficiency were lower than 2.5, 10.5, and 14%, respectively. The LOD's achieved for K+, Na+, and Li+ were 4.9, 6.8, and 9.0 μM, respectively. The clinical feasibility of the proposed approach was successfully demonstrated with the quantitative analysis of K+ and Na+ in tear samples. The concentration levels found for K+ and Na+ were, respectively, 20.8 ± 0.1 mM and 101.2 ± 0.1 mM for sample #1, and 20.4 ± 0.1 mM and 111.4 ± 0.1 mM for sample #2.
Electrochemical sensors based on graphite and polymers have emerged as powerful analytical tools for bioanalytical applications. However, most of the fabrication processes are not environmentally ...friendly because they often involve the use of toxic reagents and generate waste. This study describes an alternative method to produce flexible electrodes in plastic substrates using graphite powder and thermal laminating sheets by solid–solid deposition through hot compression, without the use of hazardous chemical reagents. The electrodes developed through the proposed approach have successfully demonstrated flexibility, robustness, reproducibility (relative standard deviation around 6%), and versatility. The electrodes were thoroughly characterized by cyclic voltammetry, electrochemical impedance spectroscopy, Raman spectroscopy, and scanning electron microscopy. As a proof of concept, the electrode surfaces were modified with bismuth and used for zinc analysis in sweat. The modified electrodes presented linearity (R 2 = 0.996) for a wide zinc concentration range (50–2000 ppb) and low detection limit (4.31 ppb). The proposed electrodes were tested using real sweat samples and the achieved zinc concentrations did not differ statistically from the data obtained by atomic absorption spectroscopy. To allow wearable applications, a 3D-printed device was fabricated, integrated with the proposed electrochemical system, and fixed at the abdomen by using an elastic tape to collect, store, and analyze the sweat sample. The matrix effect test was performed, spiking the real sample with different zinc levels, and the recovery values varied between 85 and 106%, thus demonstrating adequate accuracy and robustness of the flexible electrodes developed based on the proposed fabrication method.
3D printing has revolutionized the manufacturing process of microanalytical devices by enabling the automated production of customized objects. This technology promises to become a fundamental tool, ...accelerating investigations in critical areas of health, food, and environmental sciences. This microfabrication technology can be easily disseminated among users to produce further and provide analytical data to an interconnected network towards the Internet of Things, as 3D printers enable automated, reproducible, low-cost, and easy fabrication of microanalytical devices in a single step. New functional materials are being investigated for one-step fabrication of highly complex 3D printed parts using photocurable resins. However, they are not yet widely used to fabricate microfluidic devices. This is likely the critical step towards easy and automated fabrication of sophisticated, complex, and functional 3D-printed microchips. Accordingly, this review covers recent advances in the development of 3D-printed microfluidic devices for point-of-care (POC) or bioanalytical applications such as nucleic acid amplification assays, immunoassays, cell and biomarker analysis and organs-on-a-chip. Finally, we discuss the future implications of this technology and highlight the challenges in researching and developing appropriate materials and manufacturing techniques to enable the production of 3D-printed microfluidic analytical devices in a single step.
Display omitted
•3D printing technology is a trend in manufacturing microfluidic devices.•Advances in bioanalytical applications on 3D-printed microfluidic devices are presented.•A comparison of the advantages and disadvantages of major 3D printing methods was addressed.•The Internet of Things can help users to potentiate 3D printing technology.•Challenges and future impact of 3D printing in bioanalytical research are discussed.
This study describes the development of a new electrochemical paper-based analytical device (ePAD) on alumina sandpaper substrate through a pencil-drawing process for square wave voltammetry ...measurements of midazolam maleate used as a “date rape drug” in beverages. The proposed ePAD was assembled on a reusable 3D printed holder to delimit its geometric area and ensure better robustness. The ePAD was characterized by scanning electron microscopy, cyclic voltammetry, electrochemical impedance spectroscopy and Raman spectroscopy. The direct drawing of ePADs on sandpaper platforms through a graphite pencil has offered suitable repeatability (RSD = 1.0%) and reproducibility (RSD = 4.0%) using Fe(CN)64– as redox probe. The proposed ePAD provided linear behaviour in the midazolam maleate concentration range between 2.5 and 150 mg L−1 and a limit of detection of 2.0 mg L−1. The feasibility of the ePAD for forensic application was successfully demonstrated through the detection of midazolam in different beverages (water, beer, liquor, and vodka). The intended application revealed low interference of other compounds present in beverages. Based on the achieved results, the proposed ePAD has offered great accuracy with no statistical difference at 95% confidence level from the data recorded by high performance liquid chromatography. The operational simplicity and the robustness ensured by the assembling on a reusable 3D printed holder make the ePAD drawn on sandpaper platform a powerful and promising analytical tool for the analysis of “date rape drugs” opening new possibilities for on-site forensic investigations.
Display omitted
•Sandpaper substrate was explored to fabricate electrochemical devices through pencil drawing protocol.•ePADs were assembled on a reusable 3D-printed holder and covered with PDMS to define the geometric area.•The forensic feasibility was demonstrated through the detection of date rape drug.•The achieved results revealed good agreement with the data recorded using HPLC.•The proposed assembled device offered operational simplicity and an environmentally friendly strategy.
The adulteration of whiskey with analgesics and sedation drugs has been a common practice to prevent hangover the following day and promote loss of consciousness. In both situations, the portable and ...low cost detection platforms are of paramount importance for forensic investigations. This report describes the use of electrochemical paper‐based analytical devices (ePADs) fabricated by pencil drawing for detecting metamizole, paracetamol and midazolam maleate in whiskey. Different types of paper substrates and graphite pencils were initially characterized with ferrocyanide. The best results were achieved using vegetal paper and Aquarelle/6B pencils. ePADs revealed a decrease in current signal indicating a short lifetime, thus limiting their use to disposable sensors. Despite the short lifetime, the graphite pencil ePADs revealed good electrochemical reproducibility (RSD=3.3 %). The forensic feasibility of the proposed ePADs was demonstrated through the analysis of metamizole and paracetamol in whiskey. The limit of detection (LOD) achieved for paracetamol and metamizole were 45 and 20 mg L−1, respectively. ePADs were also tested to detect midazolam maleate in whiskey. The signal recorded exhibited linear correlation in a wide concentration range (25–1000 mg L−1) and a LOD of ca. 5 mg L−1. Considering the disposability and operational simplicity, ePADs offer a good strategy for detecting adulterations in alcoholic beverages at the point‐of‐need.
We describe the assembly of a hybrid electrophoresis device that contains fused silica capillaries interconnected to a microfabricated interface in a cross format for the determination of inorganic ...cations in biological samples. The sample transport in the proposed hybrid device was performed under gated injection mode and the separations were monitored with a capacitively coupled contactless conductivity detector. The capillary extremities were inserted into polypropylene tubes to create solution reservoirs. Sensing electrodes were produced using stainless‐steel hypodermic needles previously cut with 2.0 mm length. The running composition and injection time were optimized and the best results were found using 50 mmol/L lactic acid, 20 mmol/L histidine and 3 mmol/L 18‐crown‐6 ether, and an electrokinetic injection time of 15 s. The separation of six inorganic cations was achieved with baseline resolution, and efficiencies were between 9.1 × 103 and 5.4 × 104 plates/m. The proposed hybrid device was explored for determining the concentration levels of inorganic cations in urine, saliva, and tear samples, employing Li+ as an internal standard. The achieved results were in good agreement with the data reported in the literature. The reliability of the proposed method ranged from 93 to 98%, thus suggesting satisfactory accuracy for bioanalytical applications.
This study describes an inexpensive and nonconventional soft‐embossing protocol to produce microfluidic devices in poly(methyl methacrylate) (PMMA). The desirable microfluidic structure was ...photo‐patterned in a poly(vinyl acetate) (PVAc) film deposited on glass substrate to produce a low‐relief master. Then, this template was used to generate a high‐relief pattern in stiffened PDMS by increasing of curing agent /monomer ratio (1:5) followed by thermal aging in a laboratory oven (200°C for 24 h). The stiffened PDMS masters were used to replicate microfluidic devices in PMMA based on soft embossing at 220–230°C and thermal sealing at 140°C. Both embossing and sealing stages were performed by using binder clips. The proposed protocol has ensured the replication of microfluidic devices in PMMA with great fidelity (>94%). Examples of MCE devices, droplet generator devices and spot test array were successfully demonstrated. For testing MCE devices, a mixture containing inorganic cations was selected as model and the achieved analytical performance did not reveal significant difference from commercial PMMA devices. Water droplets were successfully generated in an oil phase at rate of ca. 60 droplets/min (fixing the continuous phase flow rate at 100 μL/h) with size of ca. 322 ± 6 μm. Glucose colorimetric assay was performed on spot test devices and good detectability level (5 μmol/L) was achieved. The obtained results for two artificial serum samples revealed good agreement with the certified concentrations. Based on the fabrication simplicity and great analytical performance, the proposed soft‐embossing protocol may emerge as promising approach for manufacturing PMMA devices.
Display omitted
•Microfluidic devices containing integrated sensing electrodes were fabricated by 3D printing.•Electrodes were printed on conductive polymer and used for conductivity ...measurements.•Microchannels were printed on ABS polymer and integrated with sensing electrodes plate.•Oil and water droplets were generated and measured in the proposed microfluidic device.•The integrated device was fabricated within 30min and exhibited low cost ($ 0.80 per device).
This report describes the 3D printing of integrated microfluidic platforms containing microchannels and embedded sensing electrodes for capacitively coupled contactless conductivity detection (C4D). Sensing electrodes were printed on poly(lactic acid) filament doped with carbon nanotubes and then integrated with fluidic channels printed on acrylonitrile butadiene styrene. The proposed microfluidic chips were explored to generate and measure the size of microdroplets based on C4D measurements. To the best of our knowledge, this is the first report showing the entire fabrication of an integrated platform by 3D printing as well as its use for measuring the size of droplets. The proof-of-concept was successfully demonstrated by generating oil droplets in an aqueous phase and water droplets in an oil phase. The droplet sizes were estimated based on their residence time within the detection cell in association with the flow velocity. According to the data achieved by C4D measurements, the length of water droplets decreased from 3.4±0.1 to 2.3±0.1mm when the total flow rate raised from 15 to 55μLmin−1. For oil droplets, length values ranged from 3.6±0.1 to 2.4±0.1mm at the same flow rate range. The achieved results exhibited an exponential correlation with the data obtained by optical measurements.
This study reports, for the first time, the possibility to manufacture analytical devices on polyester substrates using a cutting printer. The protocol involves the design of a layout in a graphical ...software, the cut into polyester films and the lamination against one or multiple polyester films coated with a thermosensitive layer. The feasibility of the proposed approach was demonstrated through the fabrication of 96-microwell plates, 3D microfluidic mixing and distance-based microfluidic devices. The printer has enabled cutting microchannels wider than 300 μm on polyester films and a thickness of 250 μm. Urea and glucose assays were performed on microwell plates aiming for their quantification in artificial urine and serum samples. The presented results revealed good agreement with the expected values. The complexation reaction between Fe2+ and o-phenanthroline was selected as model to investigate the feasibility of the 3D mixing device. Absorbance measurements were recorded for the reaction product performed in both on and off-chip modes. Considering the achieved data, the on-chip mixing exhibited similar behavior when compared to off-chip reaction, thus demonstrating to be efficient to perform mixtures due to the turbulence generated inside three-dimensional channels. Lastly, a distance-based device was designed to detect H2O2 based on the displacement of a dye plug promoted by the oxygen generation using a copper-modified paper sheet. The distance-based peroxymeter revealed a linear behavior in the concentration range between 1 and 5% (v/v) and a LOD equal to 0.5% (65.2 mM). Based on the results herein reported, the proposed method represents a simple and alternative protocol to produce microdevices, using affordable and inexpensive raw materials, within 10 min, and at a cost lower than US$ 0.10 per unit.
Display omitted
•A cutting printer was explored to produce analytical devices on polyester films.•The fabrication protocol was able to create microchannels wider than 300 μm.•Microwell plate, 3D mixing and distance-based devices were successfully presented.•The unit cost of the proposed device was estimated to be cheaper than US$ 0.10.•The polymeric devices revealed great potential for bioanalytical applications.
This chapter describes the development of paper-based microchip electrophoresis (pME) devices for the separation of clinically relevant compounds. pME were fabricated by laser cut and thermal ...lamination process using polyester pouches. In addition, hand-drawn pencil electrodes were integrated to the device to perform capacitively coupled contactless conductivity detection (C
D). Finished device costs less than US$ 0.10 and did not require either sophisticated instrumentation or clean room facilities. Furthermore, pME is lightweight, easy to handle, flexible, and robust. pME-C
D device revealed an excellent capacity to separate BSA and creatinine in less than 150 s with baseline resolution. The device proposed in this chapter has proven to be a good alternative as a platform for the diagnosis of diseases from renal disorders such as diabetes mellitus and heart disease.
