Advanced diagnostic technologies, such as polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), have been widely used in well-equipped laboratories. However, they are not ...affordable or accessible in resource-limited settings due to the lack of basic infrastructure and/or trained operators. Paper-based diagnostic technologies are affordable, user-friendly, rapid, robust, and scalable for manufacturing, thus holding great potential to deliver point-of-care (POC) diagnostics to resource-limited settings. In this review, we present the working principles and reaction mechanism of paper-based diagnostics, including dipstick assays, lateral flow assays (LFAs), and microfluidic paper-based analytical devices (μPADs), as well as the selection of substrates and fabrication methods. Further, we report the advances in improving detection sensitivity, quantification readout, procedure simplification and multi-functionalization of paper-based diagnostics, and discuss the disadvantages of paper-based diagnostics. We envision that miniaturized and integrated paper-based diagnostic devices with the sample-in-answer-out capability will meet the diverse requirements for diagnosis and treatment monitoring at the POC.
•Chip-based and paper-based analytical devices are compared.•Substrates, fabrication methods, working principles and reaction mechanisms of paper-based diagnostic devices are presented.•Current advances and trends in development of paper-based diagnostics are reviewed.•Disadvantages of paper-based diagnostics are discussed.•Perspectives of paper-based diagnostics are envisioned.
Much effort has been made to engineer artificial fiber‐shaped cellular constructs that can be potentially used as muscle fibers or blood vessels. However, existing microfiber‐based approaches for ...culturing cells are still limited to 2D systems, compatible with a restricted number of polymers (e.g., alginate) and always lacking in situ mechanical stimulation. Here, a simple, facile, and high‐throughput technique is reported to fabricate 3D cell‐laden hydrogel microfibers (named hydrogel noodles), inspired by the fabrication approach for Chinese Hele noodle. A magnetically actuated and noncontact method to apply tensile stretch on hydrogel noodles has also been developed. With this method, it is found that cellular strain‐threshold and saturation behaviors in hydrogel noodles differ substantially from their 2D analogs, including proliferation, spreading, and alignment. Moreover, it is shown that these cell‐laden microfibers can induce muscle myofiber formation by tensile stretching alone. This easily adaptable platform holds great potential for the creation of functional tissue constructs and probing mechanobiology in three dimensions.
C2C12 muscle myofibers within hydrogel fibers are successfully generated using a simple, facile, and high‐throughput method that is inspired by the fabrication process of Chinese noodles. The effect of mechanical tensile strain on cell viability, spreading, and proliferation is also investigated. Such an approach holds potential to create functional tissue constructs and provides insight into the mechanobiological responses of cells in three dimensions.
Paper‐based devices have been broadly used for the point‐of‐care detection of dengue viral nucleic acids due to their simplicity, cost‐effectiveness, and readily observable colorimetric readout. ...However, their moderate sensitivity and functionality have limited their applications. Despite the above‐mentioned advantages, paper substrates are lacking in their ability to control fluid flow, in contrast to the flow control enabled by polymer substrates (e.g., agarose) with readily tunable pore size and porosity. Herein, taking the benefits from both materials, the authors propose a strategy to create a hybrid substrate by incorporating agarose into the test strip to achieve flow control for optimal biomolecule interactions. As compared to the unmodified test strip, this strategy allows sensitive detection of targets with an approximately tenfold signal improvement. Additionally, the authors showcase the potential of functionality improvement by creating multiple test zones for semi‐quantification of targets, suggesting that the number of visible test zones is directly proportional to the target concentration. The authors further demonstrate the potential of their proposed strategy for clinical assessment by applying it to their prototype sample‐to‐result test strip to sensitively and semi‐quantitatively detect dengue viral RNA from the clinical blood samples. This proposed strategy holds significant promise for detecting various targets for diverse future applications.
A strategy to create a hybrid substrate by incorporating agarose into the test strip to achieve flow control for optimal biomolecule interactions is proposed. As compared to the unmodified test strip, this strategy allows sensitive detection of targets with an approximately tenfold signal improvement.
The emerging demand for cost‐effective, easily accessible, and rapid prototyping electronics fabrication calls for novel techniques to design and manufacture electronic components and devices for ...wearable functional sensing, on‐skin medical monitoring, and body‐worn energy conversion. Inspired by daily hand‐writing, innovative and ubiquitously available pens can be employed to write conductive patterns on multiple substrates; such a low‐cost, fast, and user‐friendly direct writing paradigm has recently aroused remarkable research interest as a promising electronics prototyping strategy. In this review, state‐of‐art advances in techniques for direct writing of electronics are presented, and pros and cons of each fabrication route are discussed. Emerging applications of pen‐based writing electronics are also summarized. Based on these, final conclusions, limitations and challenges, as well as ongoing perspectives are illustrated.
Inspired by daily hand‐writing, ubiquitously available pens have recently been employed to directly write electronics. Increasing demand for cost‐effective and easily accessible fabrication of electronics that also allows for rapid prototyping calls for novel techniques to design and manufacture electronics. State‐of‐art advances in pen‐based writing electronics and emerging applications are summarized.
Zirconia is gaining interest as a ceramic biomaterial for implant applications due to its biocompatibility and desirable mechanical properties. At present, zirconia-based ceramic is often seen in the ...applications of hip replacement and dental implants. This paper briefly reviews different surface modification techniques that have been applied to zirconia such as polishing, sandblasting, etching, biofunctionalization, coating, laser treatment, and ultraviolet light treatment. The cellular response of osteoblast-like cell, osteoblast cell, fibroblast, and epithelial cell to the modified surface is discussed in terms of their adhesion, proliferation, and metabolic activity. The potential of surface modification to make zirconia a successful implant material in the future is highly dependent on the establishment of successful in vitro and in vivo studies. Hence, further effort should be made in order to deepen the understanding of tissue response to the implant and the tissue regeneration process. The review concludes with future prospect of research and further challenges in developing better zirconia bioceramics.
With advances in point-of-care testing (POCT), lateral flow assays (LFAs) have been explored for nucleic acid detection. However, biological samples generally contain complex compositions and low ...amounts of target nucleic acids, and currently require laborious off-chip nucleic acid extraction and amplification processes (e.g., tube-based extraction and polymerase chain reaction (PCR)) prior to detection. To the best of our knowledge, even though the integration of DNA extraction and amplification into a paper-based biosensor has been reported, a combination of LFA with the aforementioned steps for simple colorimetric readout has not yet been demonstrated. Here, we demonstrate for the first time an integrated paper-based biosensor incorporating nucleic acid extraction, amplification and visual detection or quantification using a smartphone. A handheld battery-powered heating device was specially developed for nucleic acid amplification in POC settings, which is coupled with this simple assay for rapid target detection. The biosensor can successfully detect Escherichia coli (as a model analyte) in spiked drinking water, milk, blood, and spinach with a detection limit of as low as 10-1000 CFU mL(-1), and Streptococcus pneumonia in clinical blood samples, highlighting its potential use in medical diagnostics, food safety analysis and environmental monitoring. As compared to the lengthy conventional assay, which requires more than 5 hours for the entire sample-to-answer process, it takes about 1 hour for our integrated biosensor. The integrated biosensor holds great potential for detection of various target analytes for wide applications in the near future.
Lateral flow assays (LFAs) hold great promise for point-of-care testing, especially in resource-poor settings. However, the poor sensitivity of LFAs limits their widespread applications. To address ...this, we developed a novel device by integrating dialysis-based concentration method into LFAs. The device successfully achieved 10-fold signal enhancement in Human Immunodeficiency Virus (HIV) nucleic acid detection with a detection limit of 0.1nM and 4-fold signal enhancement in myoglobin (MYO) detection with a detection limit of 1.56ng/mL in less than 25min. This simple, low-cost and portable integrated device holds great potential for highly sensitive detection of various target analytes for medical diagnostics, food safety analysis and environmental monitoring.
Display omitted
•Dialysis concentration method was firstly applied to paper-based concentration device.•Paper-based concentration device was integrated into LFAs to improve its sensitivity.•The integrated device was low-cost, simple and portable.
Electrospun polycaprolactone (PCL) nanofibers have emerged as a promising material in diverse biomedical applications due to their various favorable features. However, their application in the field ...of biosensors such as point-of-care lateral flow assays (LFA) has not been investigated. The present study demonstrates the use of electrospun PCL nanofibers as a reaction membrane for LFA. Electrospun PCL nanofibers were treated with NaOH solution for different concentrations and durations to achieve a desirable flow rate and optimum detection sensitivity in nucleic acid-based LFA. It was observed that the concentration of NaOH does not affect the physical properties of nanofibers, including average fiber diameter, average pore size and porosity. However, interestingly, a significant reduction of the water contact angle was observed due to the generation of hydroxyl and carboxyl groups on the nanofibers, which increased their hydrophilicity. The optimally treated nanofibers were able to detect synthetic Zika viral DNA (as a model analyte) sensitively with a detection limit of 0.5 nM. Collectively, the benefits such as low-cost of fabrication, ease of modification, porous nanofibrous structures and tunability of flow rate make PCL nanofibers a versatile alternative to nitrocellulose membrane in LFA applications. This material offers tremendous potential for a broad range of point-of-care applications.
PDF