Integrated microfluidic biosensors enable powerful microscale analyses in biology, physics, and chemistry. However, conventional methods for fabrication of biosensors are dependent on cleanroom-based approaches requiring facilities that are expensive and are limited in access. This is especially prohibitive toward researchers in low- and middle-income countries. In this topical review, we introduce a selection of state-of-the-art, low-cost prototyping approaches of microfluidics devices and miniature sensor electronics for the fabrication of sensor devices, with focus on electrochemical biosensors. Approaches explored include xurography, cleanroom-free soft lithography, paper analytical devices, screen-printing, inkjet printing, and direct ink writing. Also reviewed are selected surface modification strategies for bio-conjugates, as well as examples of applications of low-cost microfabrication in biosensors. We also highlight several factors for consideration when selecting microfabrication methods appropriate for a project. Finally, we share our outlook on the impact of these low-cost prototyping strategies on research and development. Our goal for this review is to provide a starting point for researchers seeking to explore microfluidics and biosensors with lower entry barriers and smaller starting investment, especially ones from low resource settings.
This paper presents the use of a commercial quartz crystal microbalance (QCM) to investigate live-cell activity in water-based toxic solutions. The QCM used in this research has a resonant frequency of 10 MHz and consists of an AT-cut quartz crystal with gold electrodes on both sides. This QCM was transformed into a functional biosensor by integrating with polydimethylsiloxane culturing chambers. Rainbow trout gill epithelial cells were cultured on the resonators as a sensorial layer. The fluctuation of the resonant frequency, due to the change of cell morphology and adhesion, is an indicator of water toxicity. The shift in the resonant frequency provides information about the viability of the cells after exposure to toxicants. The toxicity result shows distinct responses after exposing cells to 0.526 μM of pentachlorophenol (PCP) solution, which is the Military Exposure Guidelines concentration. This research demonstrated that the QCM is sensitive to a low concentration of PCP and no further modification of the QCM surface was required.
Electrical cell-substrate impedance sensing (ECIS) is a powerful technique to monitor real-time cell behavior. In this study, an ECIS biosensor formed using two interdigitated electrode structures (IDEs) was used to monitor cell behavior and its response to toxicants. Three different sensors with varied electrode spacing were first modeled using COMSOL Multiphysics and then fabricated and tested. The silver/silver chloride IDEs were fabricated using a screen-printing technique and incorporated with polydimethylsiloxane (PDMS) cell culture wells. To study the effectiveness of the biosensor, A549 lung carcinoma cells were seeded in the culture wells together with collagen as an extracellular matrix (ECM) to promote cell attachment on electrodes. A549 cells were cultured in the chambers and impedance measurements were taken at 12-h intervals for 120 h. Cell index (CI) for both designs were calculated from the impedance measurement and plotted in comparison with the growth profile of the cells in T-flasks. To verify that the ECIS biosensor can also be used to study cell response to toxicants, the A549 cells were also treated with anti-cancer drug, paclitaxel, and its responses were monitored over 5 days. Both simulation and experimental results show better sensitivity for smaller spacing between electrodes. Graphical abstract The fabricated impedance biosensor used screen-printed silver/silver chloride IDEs. Simulation and experimental results show better sensitivity for smaller between electrodes.
Surface acoustic wave mediated transductions have been widely used in the sensors and actuators applications. In this study, a shear horizontal surface acoustic wave (SHSAW) was used for the detection of food pathogenic Escherichia coli O157:H7 (E.coli O157:H7), a dangerous strain among 225 E. coli unique serotypes. A few cells of this bacterium are able to cause young children to be most vulnerable to serious complications. Presence of higher than 1cfu E.coli O157:H7 in 25g of food has been considered as a dangerous level. The SHSAW biosensor was fabricated on 64° YX LiNbO3 substrate. Its sensitivity was enhanced by depositing 130.5nm thin layer of SiO2 nanostructures with particle size lesser than 70nm. The nanostructures act both as a waveguide as well as a physical surface modification of the sensor prior to biomolecular immobilization. A specific DNA sequence from E. coli O157:H7 having 22 mers as an amine-terminated probe ssDNA was immobilized on the thin film sensing area through chemical functionalization [(CHO-(CH2)3-CHO) and APTES; NH2-(CH2)3-Si(OC2H5)3]. The high-performance of sensor was shown with the specific oligonucleotide target and attained the sensitivity of 0.6439nM/0.1kHz and detection limit was down to 1.8femto-molar (1.8×10(-15)M). Further evidence was provided by specificity analysis using single mismatched and complementary oligonucleotide sequences.
The advent of personalized wearable devices has boosted the demand for portable, compact power sources. Compared with lithographic techniques, printed devices have lower fabrication costs, while still maintaining high throughput and precision. These factors make thick film printing or additive manufacturing ideal for the fabrication of low-cost batteries suitable for personalized devices. This article provides comprehensive guidelines for thick-film battery fabrication and characterization, with the focus on printed nickel-zinc (Ni-Zn) batteries. Ni-Zn batteries are a more environmental-friendly option compared with lithium-ion batteries (LIBs) as they are fully recyclable. In this work, important battery fundamentals have been described, especially terms of electrochemistry, basic design approaches, and the printing technology. Different design approaches, such as lateral, concentric, and stacked, are also discussed. Printed batteries can be configured as series or parallel constructions, depending on the power requirements of the application. The fabrication flow of printed battery electrodes for the laboratory-scale prototyping process starts from chemical preparation, mixing, printing, drying, pressing, stacking to finally sealing and testing. Of particular importance is the process of electrolyte injection and pouch sealing for the printed batteries to reduce leakage. This entire process flow is also compared with industrial fabrication flow for LIBs. Criteria for material and equipment selection are also addressed in this article to ensure appropriate electrode consistency and good performance. Two main testing methods cyclic voltammetry for the electrodes and charge-discharge for the battery are also explained in detail to serve as systematic guide for users to validate the functionality of their electrodes. This review article concludes with commercial applications of printed electrodes in the field of health and personalized wearable devices. This work indicates that printed Ni-Zn and other zinc alkaline batteries have a promising future. The success of these devices also opens up different areas of research, such as ink rheology, composition, and formulation of ink using sustainable sources.
The discovery of SARS-CoV-2 virus in the water bodies has been reported, and the risk of virus transmission to human via the water route due to poor wastewater management cannot be disregarded. The main source of the virus in water bodies is the sewage network systems which connects to the surface water. Wastewater-based epidemiology has been applied as an early surveillance tool to sense SARS-CoV-2 virus in the sewage network. This review discussed possible transmission routes of the SARS-CoV-2 virus and the challenges of the existing method in detecting the virus in wastewater. One significant challenge for the detection of the virus is that the high virus loading is diluted by the sheer volume of the wastewater. Hence, virus preconcentration from water samples prior to the application of virus assay is essential to accurately detect traceable virus loading. The preparation time, materials and conditions, virus type, recovery percentage, and various virus recovery techniques are comprehensively discussed in this review. The practicability of molecular methods such as Polymer-Chain-Reaction (PCR) for the detection of SARS-CoV-2 in wastewater will be revealed. The conventional virus detection techniques have several shortcomings and the potential of biosensors as an alternative is also considered. Biosensing techniques have also been proposed as an alternative to PCR and have reported detection limits of 10 pg/μl. This review serves to guide the reader on the future designs and development of highly sensitive, robust and, cost effective SARS-CoV-2 lab-on-a-chip biosensors for use in complex wastewater.
Diabetes has become a major health problem in society. Invasive glucometers, although precise, only provide discrete measurements at specific times and are unsuitable for long-term monitoring due to the injuries caused on skin and the prohibitive cost of disposables. Remote, continuous, self-monitoring of blood sugar levels allows for active and better management of diabetics. In this work, we present a radio frequency (RF) sensor based on a stepped impedance resonator for remote blood glucose monitoring. When placed on top of a human hand, this RF interdigital sensor allows detection of variation in blood sugar levels by monitoring the changes in the dielectric constant of the material underneath. The designed stepped impedance resonator operates at 3.528 GHz with a Q factor of 1455. A microfluidic device structure that imitates the blood veins in the human hand was fabricated in PDMS to validate that the sensor can measure changes in glucose concentrations. To test the RF sensor, glucose solutions with concentrations ranging from 0 to 240 mg/dL were injected into the fluidic channels and placed underneath the RF sensor. The shifts in the resonance frequencies of the RF sensor were measured using a network analyzer via its S11 parameters. Based on the change in resonance frequencies, the sensitivity of the biosensor was found to be 264.2 kHz/mg·dL-1 and its LOD was calculated to be 29.89 mg/dL.