Thread-based Microfluidic Device Research Articles

Innovative microfluidic thread electroanalytical device with automated injector: A simple, green and upgraded analytical platform for the fast and sensitive analysis of ferrous ions

Cotton thread-based microfluidic devices are attractive for analytical procedures due to advantages that include affordable cost, low consumption of reagents and minimal production of waste. The coupling of cotton-based devices to electrochemical detection, known as microfluidic thread electroanalytical device (µTED), has demonstrated vast potential. However, some aspects in the µTED concept can still be improved, such as sample injection, which, until now, has been performed exclusively with manual micropipettes. This conventional injection has some deficiencies that include the variability in the aspiration/dispensing rates and inconstancy in the position of the pipette during injections, which can impair the measurements. Here we propose a new approach to improve the injection step in µTEDs by using electronic pipettes, which we named as automated injection. This novel injection mode overcomes the aforementioned disadvantages of manual injection. Electronic pipettes control aspiration and dispensing volumes/rates electronically and offer better ergonomics. We developed a new 3D-printed platform that allows to attach the electronic pipette to the µTED and always perform injections at a fixed position, increasing reproducibility of measurements. To demonstrate the practical applicability, this approach was first utilized for analysis of ferrous ion in pharmaceutical supplements and environmental samples. The method presented a wide linear range (0.7 to 200 μmolL–1), low limit of detection (0.21 μmolL–1), good accuracy (recoveries between 96 and 103 %) and excellent precision (relative standard deviation (RSD) ≤ 3.3 %). Thus, automated injection can be a great advance and change the state-of-the-art regarding µTEDs.

Impact of Thread-based Microfluidic Devices in Modern Analysis: An Update on Recent Trends and Applications

Background: Inexpensive and disposable microfluidic sensing equipment is in strong demand which can detect biomarkers of diseases found in urine or blood. From recent studies, it has been found that multifilament threads can be used for producing low-cost microfluidic devices hence these multifilament threads act as an inexpensive alternative. Thread has various advantages to make it appropriate to be used in microfluidics-based technologies which include its low price, lightweight, easy availability, and hydrophilic nature. The use of any external pumping system is avoided by the presence of capillary channels in threads which allows the easy flow of fluid. Since thread offers more choices of materials over paper and also paper-based microfluidics preparation is expensive therefore thread-based microfluidic sensor has been considered more advantageous over paper-based microfluidic sensors. Methods: Various research reports were collected from search engines like ScienceDirect, Pub-med, ResearchGate, and Google Scholar. Further important outcomes from these reports along with basic experimental setup details have been compiled under different sections of this manuscript. Conclusion: Non-invasive or blood-free diagnosis can reduce the pain and several risk factors compared with the traditional invasive diagnosis so it is gaining more attention regarding health status monitoring. The various applications regarding thread-based devices include the detection of glucose and its determination, diagnosis of diabetes and kidney failure simultaneously, food dyes separation, sweat pH and lactate determination, selective potassium analysis, multiple antibodies detections, an assay of microbes, for acid-base titrations, as ELISA’s platform, diagnosis of infectious diseases, ion sensing, identification of blood types and detection of bio-samples, etc.

Simultaneous detection of dopamine and ascorbic acid by using a thread-based microfluidic device and multiple pulse amperometry.

This study presents a novel approach for the simultaneous detection of ascorbic acid (AA) and dopamine (DA) using an affordable and user-friendly microfluidic device. Microfluidic devices, when combined with electrochemical detectors like screen-printed electrodes (SPEs), offer numerous advantages such as portability, high sample throughput, and low reagent consumption. In this study, a 3D-printed microfluidic device called a μTED was developed, utilizing textile threads as microfluidic channels and an unmodified SPE as the amperometric detector. The method employed multiple pulse amperometry (MPA) with carefully selected potential values (+0.65 V and -0.10 V). The reduction current signals generated by dopamine o-quinone were used to calculate a correction factor for the oxidation signals of ascorbic acid, enabling simultaneous quantification. The developed microfluidic device ensured a stable flow rate of the carrier solution at 1.19 μL s-1, minimizing the consumption of samples and reagents (injection volume of 2.0 μL). Under the optimized experimental conditions, a linear range from 50 to 900 μmol L-1 was achieved for both DA and AA. The obtained sensitivities were 2.24 μA L mmol-1 for AA and 5.09 μA L mmol-1 for DA, with corresponding limits of detection (LOD) of 2.60 μmol L-1 and 1.54 μmol L-1, respectively. To confirm the effectiveness of the proposed method, it was successfully applied to analyze AA and DA in a commercial blood serum sample spiked at three different concentration levels, with a medium recovery rate of 70%. Furthermore, the MPA technique demonstrated its simplicity by enabling the simultaneous determination of AA and DA without the need for prior separation steps or the use of chemically modified electrodes.

Single-step measurement of cell-free DNA for sepsis prognosis using a thread-based microfluidic device.

Cell-free DNA (cfDNA) content in plasma has been studied as a biomarker for sepsis. Recent publications show that the cfDNA content in sepsis patients entering intensive care unit who were likely to survive had a total cfDNA concentration of 1.16 ± 0.13μg/mL compared to 4.65 ± 0.48μg/mL of non-survivors. Current methods for measuring cfDNA content in plasma were designed to amplify and measure low concentrations of specific DNA, making them unsuitable for low-cost measurement of total cfDNA content in plasma. Here, we have developed a point of care (POC) device that uses a thread silicone device as a medium to store a fluorescent dye which eliminates the need for preparatory steps, external aliquoting and dispensing of reagents, preconcentration, and external mixing while reducing the detection cost. The device was paired with a portable imaging system with an excitation filter at 472 ± 10nm and an emission filter of 520 ± 10nm that can be operated with just 100mA current supply. The device was demonstrated for use in the quantification of buffered cfDNA samples in a range 1-6μg/mL with a sensitivity of 5.72 AU/μg/mL and with cfDNA spiked in plasma with a range of 1-3μg/mL and a sensitivity of 5.43 AU/μg/mL. The results showed that the device could be used as a low-cost, rapid, and portable POC device for differentiating between survivors and non-survivors of sepsis within 20min.

Threads in tubing: an innovative approach towards improved electrochemical thread-based microfluidic devices.

Thread-based microfluidic analytical devices have received growing attention since threads have some advantages over other materials. Compared to paper, threads are also capable of spontaneously transporting fluid due to capillary action, but they have superior mechanical strength and do not require hydrophobic barriers. Therefore, thread-based microfluidic devices can be inexpensively fabricated with no need for external pumps or sophisticated microfabrication apparatus. Despite these outstanding features, achieving a controlled and continuous flow rate is still a challenging task, mainly due to fluid evaporation. Here, we overcome this challenge by inserting a cotton thread into a polyethylene tube aiming to minimize fluid evaporation. Also, a cotton piece was inserted into the outlet reservoir to improve the wicking ability of the device. This strategy enabled the fabrication of an innovative electrochemical thread in a tubing microfluidic device that was capable to hold a consistent flow rate (0.38 μL s-1) for prolonged periods, allowing up to 100 injections in a single device by simply replacing the cotton piece in the outlet reservoir. The proposed device displayed satisfactory analytical performance for selected model analytes (dopamine, hydrogen peroxide, and tert-butylhydroquinone), in addition to being successfully used for quantification of nitrite in spiked artificial saliva samples. Beyond the flow rate improvement, this "thread-in-tube" strategy ensured the protection of the fluid from external contamination while making it easier to connect the electrode array to the microchannels. Thus, we envision that the thread in a tube strategy could bring interesting improvements to thread-based microfluidic analytical devices.

A novel all-3D-printed thread-based microfluidic device with an embedded electrochemical detector: first application in environmental analysis of nitrite.

A microfluidic thread electroanalytical device (μTED) containing an embedded electrochemical detector is presented for the first time in this work. This novel device was entirely produced in an automated way using the fused deposition modeling (FDM) 3D printing technique. The main platform was fabricated with acrylonitrile butadiene styrene (ABS) filament, while the integrated electrochemical detector was produced using a commercial conductive filament composed of carbon black and polylactic acid (CB/PLA). The microfluidic channels consisted of cotton threads, which act as passive pumps, and the μTED was used for microflow injection analysis (μFIA). As a proof of concept, this μFIA system was utilized for the amperometric sensing of nitrite in natural waters. This is the first report on the use of both μTEDs and 3D-printed CB/PLA electrodes to determine this species. This fully 3D-printed μTED was characterized and all experimental and instrumental parameters related to the method were studied and optimized. Using the best conditions, the proposed approach showed a linear response in the concentration range from 8 to 200 μmol L-1 and a limit of detection (LOD) of 2.39 μmol L-1. The LOD obtained here was ca. ten-fold lower than the maximum contaminant level for nitrite in drinking water established by the Brazilian and US legislation. Moreover, the platform presented good repeatability and reproducibility (relative standard deviations (RSDs) were 2.1% and 2.5%, respectively). Lastly, the 3D-printed μTED was applied for the quantification of nitrite in well water samples and the results obtained showed good precision (RSD < 3%) and excellent concordance (relative error was ca.±3%) with those achieved by ion chromatography, used for validation.

Microfluidic devices based on textile threads for analytical applications: state of the art and prospects.

Microfluidic devices based on textile threads have interesting advantages when compared to systems made with traditional materials, such as polymers and inorganic substrates (especially silicon and glass). One of these significant advantages is the device fabrication process, made more cheap and simple, with little or no microfabrication apparatus. This review describes the fundamentals, applications, challenges, and prospects of microfluidic devices fabricated with textile threads. A wide range of applications is discussed, integrated with several analysis methods, such as electrochemical, colorimetric, electrophoretic, chromatographic, and fluorescence. Additionally, the integration of these devices with different substrates (e.g., 3D printed components or fabrics), other devices (e.g., smartphones), and microelectronics is described. These combinations have allowed the construction of fully portable devices and consequently the development of point-of-care and wearable analytical systems.

Chitosan-modified cotton thread for the preconcentration and colorimetric trace determination of Co(II)

In this work we propose a thread-based microfluidic device (μTAD) for the preconcentration and colorimetric determination of Co(II) in water using a digital image. The reaction is based on complexation of Co(II) by 4-(2-pyridylazo) resorcinol (PAR), which changes the detection zone from yellow to red. PAR is immobilized in a chitosan membrane to retain the complex in the detection zone. The designed μTAD makes it possible to preconcentrate and determine cobalt between 25 and 600 µg·L−1 with a relative standard deviation of 4% (n = 5), and a detection limit of 6.5 µg·L−1. The device permits an enhancementfactor of 11 by combining the use of a chitosan retention membrane and a sample volume of 50 µL. Recovery experiments were performed in tap water to evaluate the accuracy of the method, and the results obtained compared to a reference method presents an error no higher than 5.7%.

Fast and straightforward in-situ synthesis of gold nanoparticles on a thread-based microfluidic device for application in surface-enhanced Raman scattering detection

Cotton threads forming a microfluidic device were used for the first time to conduct a fast and straightforward Turkevich synthesis of gold nanoparticles (AuNPs) using minute amounts of reagents. Spherical AuNPs were obtained with sizes that varied from 20 to 40 nm, according to the synthesis conditions. The cotton thread also acted as physical support for the synthesized AuNPs during surface-enhanced Raman scattering (SERS) detection of crystal violet and nicotine. A calibration curve for nicotine with acceptable linearity (R2 = 0.9844) in the concentration range of 2–6 mg L−1 was obtained. The limit of detection for nicotine was 0.18 mg L−1. The proposed substrate was considered cheap, fast, and easy to be fabricated and applied in SERS detection.

A novel thread-based microfluidic device for capillary electrophoresis with capacitively coupled contactless conductivity detection

This work describes a novel thread-based microfluidic device to perform capillary electrophoresis separation and capacitively coupled contactless conductivity detection. Polyester threads with a diameter of about 315 μm were assembled (stretched) in a 3D-printed platform containing solution reservoirs and platinum electrodes. Separation of potassium, sodium, and lithium ions was achieved within 1 min with good peak resolutions and limits of detection close to 1 μmol L−1. Inversion of the electroosmotic flow direction by adding a cationic surfactant in the running electrolyte was demonstrated. The applicability of the thread-based microfluidic devices was successfully evaluated by the determination of sodium and potassium ions in commercial samples of diet soft drinks.

Cross Channel Thread-Based Microfluidic Device for Separation of Food Dyes

We described a method for electrophoretic separation of food dyes on a thread-based microfluidic analytical device. A cross channel thread-based microfluidic analytical device was fabricated and used to separate a mixture of food dyes. By controlling and adjusting the potentials applied onto four reservoirs, carmine and sunset yellow could be separated within 2 min. This method has the advantages of low cost, fast separation, and easy fabrication and operation, which make this very suitable for performing as a demonstration in universities. The students enjoyed this demonstration and presented some interesting and constructive questions after the demonstration, which indicated that the students were interested in the demonstration. This demonstration could also be modified to be a laboratory experiment which could be carried out within 3 h.

Modification of thread-based microfluidic device with polysiloxanes for the development of a sensitive and selective immunoassay

We demonstrate that polysiloxanes can be tuned to be partially hydrophilic for manipulating the fluidic flow in the pores of cotton thread-based microfluidic devices. A mixture of methanol and isopropanol was used as a diluent for siloxane precursor, which was included into the thread to enable rapid curing of polysiloxanes for fluidic control and enhance detection sensitivity. Interestingly, twelve-fold diluted polysiloxanes enabled desirable fluidic delay and optimum interaction between the targeted antigen and detection antibody-gold nanoparticles (dAb-AuNPs) in the thread-based immunoassay, generating more antigen-dAb-AuNP complexes that bound to the capture antibody (cAb) at the test zone and achieved signal enhancement (∼10-fold over unmodified device). The phenomenon of fluidic delay was evaluated by mathematical simulation, through which the fluidic movement on the polysiloxanes-coated region was observed and the simulation data was in agreement with the experimental data. This polysiloxanes-modified device could detect Salmonella enterica serotype Enteritidis (as a model analyte) in phosphate buffered saline, spiked whole milk, juice and lettuce with the detection limit of 500, 1000, 1000 and 5000 CFU/mL, respectively, which was comparable to or even more sensitive than the existing immunoassays. This work expands the application of polysiloxanes in the microfluidic devices for biomedical diagnosis, water quality monitoring, and food safety surveillance.

Recent developments in microfluidic paper-, cloth-, and thread-based electrochemical devices for analytical chemistry

AbstractThe attractive structural and mechanical properties of cellulose substrates (paper, cloth, and thread), including passive fluid transport, biocompatibility, durability, and flexibility, have attracted researchers in the past few decades to explore them as alternative microfluidic platforms. The incorporation of electrochemical (EC) sensing broadened their use for applications such as clinical diagnosis, pharmaceutical chemical analyses, food quality, and environmental monitoring. This article provides a review on the microfluidic devices constructed on paper, cloth, and thread substrates. It begins with an overview on paper-based microfluidic devices, followed by an in-depth review on the various applications of EC detection incorporated on paper-based microfluidic devices reported to date. The review on paper-based microfluidic devices attempts to convey a few perspective directions that cloth- and thread-based microfluidic devices may take in its development. Finally, the research efforts on the development and evaluation, as well as current limitations of cloth- and thread-based microfluidic devices are discussed. Microfluidic devices constructed on paper, cloth, and thread substrates are still at an early development stage (prototype) requiring several improvements in terms of fabrication, analytical techniques, and performance to become mature platforms that can be adapted and commercialized as real world products. However, they hold a promising potential as wearable devices.

Bipolar electrochemiluminescence on thread: A new class of electroanalytical sensors

This paper introduces a new and simple concept for fabricating low-cost, easy-to-use capillary microchannel (CMC) assisted thread-based microfluidic analytical devices (CMCA-μTADs) for bipolar electrochemiluminescence (BP-ECL) application. The thread with patterns of carbon screen-printed electrodes and bare thread zones (BTZs) is embedded into a CMC. Such CMCA-μTADs can produce a strong and stable BP-ECL signal, and have an extremely low cost ($0.01 per device). Interestingly, the CMCA-μTADs are ultraflexible, and can be bent with a 135° bending angle at the BTZ or with a 150° bending angle at the middle of bipolar electrode (BPE), with no loss of analytical performance. Additionally, the two commonly-used ECL systems of Ru(bpy)32+/TPA and luminol/H2O2 are applied to demonstrate the quantitative ability of the BP-ECL CMCA-μTADs. It has been shown that the proposed devices have successfully fulfilled the detection of TPA and H2O2, with detection limits of 0.00432mM and 0.00603mM, respectively. Based on the luminol/H2O2 ECL system, the CMCA-μTADs are further applied for the glucose measurement, with the detection limit of 0.0205mM. Finally, the applicability and validity of the CMCA-μTADs are demonstrated for the measurements of H2O2 in milk, and glucose in human urine and serum. The results indicate that the proposed devices have the potential to become an important new tool for a wide range of applications.

Surface Modified Thread-Based Microfluidic Analytical Device for Selective Potassium Analysis.

This paper presents a thread-based microfluidic device (μTAD) that includes ionophore extraction chemistry for the optical recognition of potassium. The device is 1.5 cm × 1.0 cm and includes a cotton thread to transport the aqueous sample via capillary wicking to a 5 mm-long detection area, where the recognition chemistry is deposited that reaches equilibrium in 60 s, changing its color between blue and magenta. A complete characterization of the cotton thread used as well as the sensing element has been carried out. The imaging of the μTAD with a digital camera and the extraction of the H coordinate of the HSV color space used as the analytical parameter make it possible to determine K(I) between 2.4 × 10(-5) and 0.95 M with a precision better than 1.3%.

Plasma treatments of wool fiber surface for microfluidic applications

Recent progress in health diagnostics has led to the development of simple and inexpensive systems. Thread-based microfluidic devices allow for portable and inexpensive field-based technologies enabling medical diagnostics, environmental monitoring, and food safety analysis.However, controlling the flow rate of wool thread, which is a very important part of thread-based microfluidic devices, is quite difficult. For this reason, we focused on thread-based microfluidics in the study. We developed a method of changing the wettability of hydrophobic thread, including wool thread.Thus, using natural wool thread as a channel, we demonstrate herein that the manipulation of the liquid flow, such as micro selecting and micro mixing, can be achieved by applying plasma treatment to wool thread. In addition to enabling the flow control of the treated wool channels consisting of all natural substances, this procedure will also be beneficial for biological sensing devices. We found that wools treated with various gases have different flow rates. We used an atmospheric plasma with O2, N2 and Ar gases.

Flow Manipulation in Thread-Based Microfluidics by Tuning the Wettability of Wool.

Recent progress in thread-based microfluidic devices has provided portable and inexpensive field-based technologies enabling medical diagnostics, environmental monitoring, and food safety analysis. However, capillary-driven liquid flow in a single thread, a crucial aspect of thread-based microfluidics, is difficult to control. Among potential materials, hydrophobic wool thread is an appropriate candidate for liquid flow control in thread-based microfluidics because its wettability can be readily tuned by the introduction of a natural color pigment, thereby manipulating flow. Thus, utilizing natural wool thread as a channel, we demonstrate here that liquid flow manipulations, such as microselecting and micromixing, can be achieved by coating the complex Al(III) (Alum) brazilein onto wool thread. In addition to enabling flow control, the coated wool channels consisting entirely of naturally occurring substances will be beneficial for biological sensing devices.

Thread-based microfluidic system for detection of rapid blood urea nitrogen in whole blood

This study develops a thread-based microfluidic device with variable volume injection capability and 3-dimensional (3D) detection electrodes for capillary electrophoresis electrochemical (CE–EC) detection of blood urea nitrogen (BUN) in whole blood. A poly methyl methacrylate (PMMA) substrate with concave 3D electrodes produced by the hot embossing method is used to enhance the sensing performance of the CE–EC system. Results show that the chip with 3D sensing electrodes exhibits a measured current response nine times higher and signal-to-noise ratio five times higher when compared to the peak responses obtained using a chip with conventional 2D sensing electrodes. In addition, the developed thread-based microfluidic system is capable of injecting variable sample volumes into the separation thread simply by wrapping the injection thread different numbers of times around the separation thread. The peak S/N ratio can be further enhanced with this simple approach. Results also indicate that the CE–EC system exhibits good linear dynamic range for detecting a urea sample in concentrations from 0.1 to 10.0 mM (R 2 = 0.9848), which is suitable for adoption in detecting the BUN concentration in human blood (1.78–7.12 mM). Separation and detection of the ammonia ions converted from BUN in whole blood is successfully demonstrated in the present study, with the developed thread-based microfluidic system providing a low-cost, high-performance method for detecting BUN in human blood.

Retraction Note: Electrophoresis separation and electrochemical detection on a novel thread-based microfluidic device

This article describes a thread-based microfluidic system for rapid and low-cost electrophoresis separation and electrochemical (EC) detection of ion samples. Instead of using liquid channel for sample separation, thin polyester threads of various diameters are used as the routes for separating the samples with electrophoresis. Hot-pressed PMMA chip with protruding sleeper structures are adopted to set up the polyester threads and for electrochemical detecting the ion samples on the thread. Plasma treatment greatly improves the wetability of thin threads and surface quality of the threads. The measured electrical currents on plasma-treated threads are ten times greater than the threads without treatment. Results indicate that nice redox signals can be obtained by measuring ferric cyanide salt on the polyester thread. The estimated detection limit for EC sensing of potassium ferricyanide (K3Fe(CN)6) is around 6.25 μM using the developed thread-based microfluidic device. Mixed-ion samples (Cl−, Br−, and I−) and bio-sample are successfully separated and detected using the developed thread-based microfluidic device.

RETRACTED ARTICLE: Electrophoresis separation and electrochemical detection on a novel thread-based microfluidic device

RETRACTED ARTICLE: Electrophoresis separation and electrochemical detection on a novel thread-based microfluidic device