RESUMO

OBJECTIVE: To evaluate the efficacy of microchips and 3D microsensors in the measurement of orthodontic forces. METHODS: Through September 2023, comprehensive searches were conducted on PubMed/MEDLINE, SCOPUS and SCIELO without restrictions. RESULTS: After removing duplicate entries and applying the eligibility criteria, 23 studies were included for analysis. All the studies were conducted in vitro, and slightly more than half of them were centred on evaluating orthodontic forces exerted by aligners. Eight utilized microchips as measurement tools, while the remaining studies made use of 3D microsensors for their assessments. In the context of fixed appliances, key findings included a high level of agreement in 3-dimensional orthodontic force detection between simulation results and actual applied forces. Incorporating critical force-moment combinations during smart bracket calibration reduced measurement errors for most components. Translational tooth movement revealed a moment-to-force ratio, aligning with the bracket's centre of resistance. The primary findings in relation to aligners revealed several significant factors affecting the forces exerted by them. Notably, the foil thickness and staging were found to have a considerable impact on these forces, with optimal force transmission occurring at a layer height of 150 µm. Furthermore, the type of material used in 3D-printing aligners influenced the force levels, with attachments proving effective in generating extrusive forces. Deliberate adjustments in aligner thickness were observed to alter the forces and moments generated. CONCLUSIONS: Microchips and 3D sensors provide precise and quantitative measurements of orthodontic forces in in vitro studies, enabling accurate monitoring and control of tooth movement.

RESUMO

Proteins are important molecules involved in an immensely large number of biological processes. Being capable of manipulating proteins is critical for developing reliable and affordable techniques to analyze and/or detect them. Such techniques would enable the production of therapeutic agents for the treatment of diseases or other biotechnological applications (e.g., bioreactors or biocatalysis). Microfluidic technology represents a potential solution to protein manipulation challenges because of the diverse phenomena that can be exploited to achieve micro- and nanoparticle manipulation. In this review, we discuss recent contributions made in the field of protein manipulation in microfluidic systems using different physicochemical principles and techniques, some of which are miniaturized versions of already established macro-scale techniques.

Assuntos

RESUMO

Although microparticles are frequently used in chemistry and biology, their effectiveness largely depends on the homogeneity of their particle size distribution. Microfluidic devices to separate and purify particles based on their size have been developed, but many require expensive cleanroom manufacturing processes. A cost-effective, passive microfluidic separator is presented, capable of efficiently sorting and purifying particles spanning the size range of 15 µm to 40 µm. Fabricated from Polymethyl Methacrylate (PMMA) substrates using laser ablation, this device circumvents the need for cleanroom facilities. Prior to fabrication, rigorous optimization of the device's design was carried out through computational simulations conducted in COMSOL Multiphysics. To gauge its performance, chitosan microparticles were employed as a test case. The results were notably promising, achieving a precision of 96.14 %. This quantitative metric underscores the device's precision and effectiveness in size-based particle separation. This low-cost and accessible microfluidic separator offers a pragmatic solution for laboratories and researchers seeking precise control over particle sizes, without the constraints of expensive manufacturing environments. This innovation not only mitigates the limitations tied to traditional cleanroom-based fabrication but also widens the horizons for various applications within the realms of chemistry and biology.

RESUMO

Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola, collectively recognized as periodontopathogens within the red complex, have been extensively studied in clinical samples collected from individuals with periodontitis. A lab-on-a-chip (LOC) is a miniature mechanism that integrates various laboratory operations onto a single microchip or a small-scale platform. This systematic review evaluates the application of LOC technology in identifying microorganisms from the red complex. This study adhered to PRISMA recommendations, and the review process encompassed several databases. In the electronic search, a total of 58 reports were found, and ultimately, 10 studies were considered relevant for inclusion. All these studies described effective, rapid, and reliable LOC systems for detecting and amplifying P. gingivalis, T. forsythia, and T. denticola. Compared to traditional methods, the LOC approach demonstrated minimal reagent requirements. Additionally, the results indicated that the amplification process took approximately 2 to 8 min, while detection could be completed in as little as 2 min and 40 s, resulting in a total experimental duration of around 11 min. Integrating miniaturization, speed, accuracy, and automation within microchip platforms makes them promising tools for detecting and amplifying microorganisms associated with the red complex in periodontal diseases.

RESUMO

Background and Objectives: Staphylococcus aureus is a prevalent bacterium capable of inducing various infections, including skin and soft tissue infections, bloodstream infections, pneumonia, and surgical site infections. The emergence of antimicrobial resistance in S. aureus, particularly methicillin-resistant S. aureus, has raised substantial concerns within global healthcare settings. Prior to antibiotic prescription, the ideal approach is antimicrobial susceptibility testing (AST); however, this is frequently perceived as excessively complex and time-intensive. Lab-on-a-chip (LOC) technology holds promise in addressing these challenges and advancing fundamental microbiological research while also aiding in the development of therapeutic strategies. This systematic review aims to evaluate the potential utility of LOC for AST of S. aureus. Materials and Methods: This study adhered to the PRISMA guidelines. Various databases, including SCOPUS, PubMed/MEDLINE, SCIELO, and LILACS, in addition to gray literature sources, were employed in the review process. Results: Sixteen studies were included in this systematic review. All these studies detailed the effectiveness, rapidity, and predictability of LOC systems for assessing S. aureus susceptibility to various antibiotics. When comparing the LOC approach to traditional manual methods, it was evident that LOC requires a minimal quantity of reagents. Furthermore, most studies reported that the entire LOC procedure took 10 min to 7 h, with results being equally accurate as those obtained through traditional AST protocols. Conclusions: The potential application of LOC for AST of S. aureus is emphasized by its ability to provide rapid access to minimum inhibitory concentration data, which can substantially aid in selecting the most suitable antibiotics and dosages for treating challenging infections caused by this microorganism. Moreover, the rapid AST facilitated by LOC holds promise for enhancing the appropriateness and efficacy of therapy in clinical settings.

Assuntos

RESUMO

Microfluidic platforms for clinical use are a promising translational strategy for cancer research specially for drug screening. Identifying cancer stem cells (CSC) using sphere culture techniques in microfluidic devices (MDs) showed to be better reproducing physiological responses than other in vitro models and allow the optimization of samples and reagents. We evaluated individual sphere proliferation and stemness toward chemotherapeutic treatment (CT) with doxorubicin and cisplatin in bladder cancer cell lines (MB49-I and J82) cultured in MDs used as CSC treatment response platform. Our results confirm the usefulness of this device to evaluate the CT effect in sphere-forming efficiency, size, and growth rate from individual spheres within MDs and robust information comparable to conventional culture plates was obtained. The expression of pluripotency genetic markers (Oct4, Sox2, Nanog, and CD44) could be analyzed by qPCR and immunofluorescence in spheres growing directly in MDs. MDs are a suitable platform for sphere isolation from tumor samples and can provide information about CT response. Microfluidic-based CSC studies could provide information about treatment response of cancer patients from small samples and can be a promising tool for CSC-targeted specific treatment with potential in precision medicine. KEY MESSAGES: We have designed a microfluidic platform for CSC enriched culture by tumor sphere formation. Using MDs, we could quantify and determine sphere response after CT using murine and human cell lines as a proof of concept. MDs can be used as a tumor-derived sphere isolation platform to test the effect of antitumoral compounds in sphere proliferation.

Assuntos

RESUMO

The detection of nucleic acids as specific markers of infectious diseases is commonly implemented in molecular biology laboratories. The translation of these benchtop assays to a lab-on-a-chip format demands huge efforts of integration and automation. The present work is motivated by a strong requirement often posed by molecular assays that combine isothermal amplification and CRISPR/Cas-based detection: after amplification, a 2-8 microliter aliquot of the reaction products must be taken for the subsequent reaction. In order to fulfill this technical problem, we have designed and prototyped a microfluidic device that is able to meter and aliquot in the required range during the stepped assay. The operation is achieved by integrating a porous material that retains the desired amount of liquid after removing the excess reaction products, an innovative solution that avoids valving and external actuation. The prototypes were calibrated and experimentally tested to demonstrate the overall performance (general fluidics, metering, aliquoting, mixing and reaction). The proposed aliquoting method is fully compatible with additional functions, such as sample concentration or reagent storage, and could be further employed in alternative applications beyond molecular diagnosis.

RESUMO

This chapter describes the application of genomic, transcriptomic, proteomic, and metabolomic methods in the study of SARS-CoV-2 variants of concern. We also describe the important role of machine learning tools to identify the most significant biomarker signatures and discuss the latest point-of-care devices that can be used to translate these findings to the physician's office or to bedside care. The main emphasis is placed on increasing our diagnostic capacity and predictability of disease outcomes to guide the most appropriate treatment strategies.

Assuntos

RESUMO

Microfluidics is an interdisciplinary field that encompasses both science and engineering, which aims to design and fabricate devices capable of manipulating extremely low volumes of fluids on a microscale level. The central objective of microfluidics is to provide high precision and accuracy while using minimal reagents and equipment. The benefits of this approach include greater control over experimental conditions, faster analysis, and improved experimental reproducibility. Microfluidic devices, also known as labs-on-a-chip (LOCs), have emerged as potential instruments for optimizing operations and decreasing costs in various of industries, including pharmaceutical, medical, food, and cosmetics. However, the high price of conventional prototypes for LOCs devices, generated in clean room facilities, has increased the demand for inexpensive alternatives. Polymers, paper, and hydrogels are some of the materials that can be utilized to create the inexpensive microfluidic devices covered in this article. In addition, we highlighted different manufacturing techniques, such as soft lithography, laser plotting, and 3D printing, that are suitable for creating LOCs. The selection of materials and fabrication techniques will depend on the specific requirements and applications of each individual LOC. This article aims to provide a comprehensive overview of the numerous alternatives for the development of low-cost LOCs to service industries such as pharmaceuticals, chemicals, food, and biomedicine.

RESUMO

The global need for accurate and efficient cancer cell detection in biomedicine and clinical diagnosis has driven extensive research and technological development in the field. Precision, high-throughput, non-invasive separation, detection, and classification of individual cells are critical requirements for successful technology. Lab-on-a-chip devices offer enormous potential for solving biological and medical problems and have become a priority research area for microanalysis and manipulating cells. This paper reviews recent developments in the detection of cancer cells using the microfluidics-based lab-on-a-chip method, focusing on describing and explaining techniques that use optical phenomena and a plethora of probes for sensing, amplification, and immobilization. The paper describes how optics are applied in each experimental method, highlighting their advantages and disadvantages. The discussion includes a summary of current challenges and prospects for cancer diagnosis.

Assuntos

RESUMO

A method development aimed for high-throughput and automated antibody screening holds great potential for areas ranging from fundamental molecular interactions to the discovery of novel disease markers, therapeutic targets, and monoclonal antibody engineering. Surface display techniques enable efficient manipulation of large molecular libraries in small volumes. Specifically, phage display appeared as a powerful technology for selecting peptides and proteins with enhanced, target-specific binding affinities. Here, we present a phage-selection microfluidic device wherein electrophoresis was performed under two orthogonal electric fields through an agarose gel functionalized with the respective antigen. This microdevice was capable of screening and sorting in a single round high-affinity phage-displayed antibodies against virus glycoproteins, including human immunodeficiency virus-1 glycoprotein 120 or the Ebola virus glycoprotein (EBOV-GP). Phages were differentially and laterally swept depending on their antigen affinity; the high-affinity phages were recovered at channels proximal to the application site, whereas low-affinity phages migrated distal after electrophoresis. These experiments proved that the microfluidic device specifically designed for phage-selection is rapid, sensitive, and effective. Therefore, this is an efficient and cost-effective method that allowed highly controlled assay conditions for isolating and sorting high-affinity ligands displayed in phages.

Assuntos

RESUMO

Temperature is a critical-yet sometimes overlooked-parameter in microfluidics. Microfluidic devices can experience heating inside their channels during operation due to underlying physicochemical phenomena occurring therein. Such heating, whether required or not, must be monitored to ensure adequate device operation. Therefore, different techniques have been developed to measure and control temperature in microfluidic devices. In this contribution, the operating principles and applications of these techniques are reviewed. Temperature-monitoring instruments revised herein include thermocouples, thermistors, and custom-built temperature sensors. Of these, thermocouples exhibit the widest operating range; thermistors feature the highest accuracy; and custom-built temperature sensors demonstrate the best transduction. On the other hand, temperature control methods can be classified as external- or integrated-methods. Within the external methods, microheaters are shown to be the most adequate when working with biological samples, whereas Peltier elements are most useful in applications that require the development of temperature gradients. In contrast, integrated methods are based on chemical and physical properties, structural arrangements, which are characterized by their low fabrication cost and a wide range of applications. The potential integration of these platforms with the Internet of Things technology is discussed as a potential new trend in the field.

Assuntos

RESUMO

Paper-based microfluidic systems have emerged as one of the most promising technologies for developing point-of-care diagnostic platforms (POCT) for detecting and monitoring various diseases. Saliva is a non-invasive biofluid easily collected, transported, and stored. Due to its accessibility and connection to systemic diseases, saliva is one of the best candidates for medical advancement at the point of care, where people can easily monitor their health. However, saliva is a complex mixture of DNA, RNA, proteins, exosomes, and electrolytes. Thus, nucleic acid separation from the salivary components is essential for PCR applications. Paper membranes are a highly porous and foldable structure capable of transporting fluids without pumps and sophisticated systems. The current work presents an insight into simulations for nucleic acid extraction on three types of porous paper membranes for use in point-of-care devices. The flow fluid model is solved on a COMSOL Multiphysics 5.3 free version platform, and the results are compared with experimental assays. The results show that pore uniformity, wet strength, porosity, and functional groups of MF1™ and Fusion 5™ paper membranes are vital parameters affecting nucleic acid extraction and PCR amplification efficiency.

RESUMO

Lab-on-a-Chip (LoC) devices are described as versatile, fast, accurate, and low-cost platforms for the handling, detection, characterization, and analysis of a wide range of suspended particles in water-based environments. However, for gas-based applications, particularly in atmospheric aerosols science, LoC platforms are rarely developed. This review summarizes emerging LoC devices for the classification, measurement, and identification of airborne particles, especially those known as Particulate Matter (PM), which are linked to increased morbidity and mortality levels from cardiovascular and respiratory diseases. For these devices, their operating principles and performance parameters are introduced and compared while highlighting their advantages and disadvantages. Discussing the current applications will allow us to identify challenges and determine future directions for developing more robust LoC devices to monitor and analyze airborne PM.

Assuntos

RESUMO

Exosomes are small extracellular vesicles that can be obtained from several body fluids such as blood and urine. Since these vesicles can carry biomarkers and other cargo, they have application in healthcare diagnostics and therapeutics, such as liquid biopsies and drug delivery. Yet, their identification and separation from a sample remain challenging due to their high degree of heterogeneity and their co-existence with other bioparticles. In this contribution, we review the state-of-the-art on electrical techniques and methods to displace, selectively trap/isolate, and detect/characterize exosomes in microfluidic devices. Although there are many reviews focused on exosome separation using benchtop equipment, such as ultracentrifugation, there are limited reviews focusing on the use of electrical phenomena in microfluidic devices for exosome manipulation and detection. Here, we highlight contributions published during the past decade and present perspectives for this research field for the near future, outlining challenges to address in years to come.

Assuntos

RESUMO

Malaria affects 228 million people worldwide each year, causing severe disease and worsening the conditions of already vulnerable populations. In this review, we explore how malaria has been detected in the past and how it can be detected in the future. Our primary focus is on finding new directions for low-cost diagnostic methods that unspecialized personnel can apply in situ. Through this review, we show that microfluidic devices can help pre-concentrate samples of blood infected with malaria to facilitate the diagnosis. Importantly, these devices can be made cheaply and be readily deployed in remote locations.

RESUMO

Electrokinetically driven insulator-based microfluidic devices represent an attractive option to manipulate particle suspensions. These devices can filtrate, concentrate, separate, or characterize micro and nanoparticles of interest. Two decades ago, inspired by electrode-based dielectrophoresis, the concept of insulator-based dielectrophoresis (iDEP) was born. In these microfluidic devices, insulating structures (i.e., posts, membranes, obstacles, or constrictions) built within the channel are used to deform the spatial distribution of an externally generated electric field. As a result, particles suspended in solution experience dielectrophoresis (DEP). Since then, it has been assumed that DEP is responsible for particle trapping in these devices, regardless of the type of voltage being applied to generate the electric field-direct current (DC) or alternating current. Recent findings challenge this assumption by demonstrating particle trapping and even particle flow reversal in devices that prevent DEP from occurring (i.e., unobstructed long straight channels stimulated with a DC voltage and featuring a uniform electric field). The theory introduced to explain those unexpected observations was then applied to conventional "DC-iDEP" devices, demonstrating better prediction accuracy than that achieved with the conventional DEP-centered theory. This contribution summarizes contributions made during the last two decades, comparing both theories to explain particle trapping and highlighting challenges to address in the near future.

Assuntos

RESUMO

Research on alternatives to the use of animal models and cell cultures has led to the creation of organ-on-a-chip systems, in which organs and their physiological reactions to the presence of external stimuli are simulated. These systems could even replace the use of human beings as subjects for the study of drugs in clinical phases and have an impact on personalized therapies. Organ-on-a-chip technology present higher potential than traditional cell cultures for an appropriate prediction of functional impairments, appearance of adverse effects, the pharmacokinetic and toxicological profile and the efficacy of a drug. This potential is given by the possibility of placing different cell lines in a three-dimensional-arranged polymer piece and simulating and controlling specific conditions. Thus, the normal functioning of an organ, tissue, barrier, or physiological phenomenon can be simulated, as well as the interrelation between different systems. Furthermore, this alternative allows the study of physiological and pathophysiological processes. Its design combines different disciplines such as materials engineering, cell cultures, microfluidics and physiology, among others. This work presents the main considerations of OoC systems, the materials, methods and cell lines used for their design, and the conditions required for their proper functioning. Examples of applications and main challenges for the development of more robust systems are shown. This non-systematic review is intended to be a reference framework that facilitates research focused on the development of new OoC systems, as well as their use as alternatives in pharmacological, pharmacokinetic and toxicological studies.

RESUMO

This article shows the development of a computer-controlled lab-on-a-chip device with three magnetohydrodynamic (MHD) pumps and a pneumatic valve. The chip was made of a stack of layers of polymethylmethacrylate (PMMA), cut using a laser engraver and thermally bonded. The MHD pumps were built using permanent magnets (neodymium) and platinum electrodes, all of them controlled by an Arduino board and a set of relays. The implemented pumps were able to drive solutions in the open channels with a flow rate that increased proportionally with the channel width and applied voltage. To address the characteristic low pressures generated by this kind of pump, all channels were interconnected. Because the electrodes were immersed in the electrolyte, causing electrolysis and pH variations, the composition and ionic strength of the electrolyte solution were controlled. Additionally, side structures for releasing bubbles were integrated. With this multi-pump and valve solution, the device was used to demonstrate the possibility of performing an injection sequence in a system that resembles a traditional flow injection analysis system. Ultimately, the results demonstrate the possibility of performing injection sequences using an array of MHD pumps that can perform fluid handling in the 0-5 µL s-1 range.

RESUMO

Point-of-care (PoC) diagnostics is promising for early detection of a number of diseases, including cancer, diabetes, and cardiovascular diseases, in addition to serving for monitoring health conditions. To be efficient and cost-effective, portable PoC devices are made with microfluidic technologies, with which laboratory analysis can be made with small-volume samples. Recent years have witnessed considerable progress in this area with "epidermal electronics", including miniaturized wearable diagnosis devices. These wearable devices allow for continuous real-time transmission of biological data to the Internet for further processing and transformation into clinical knowledge. Other approaches include bluetooth and WiFi technology for data transmission from portable (non-wearable) diagnosis devices to cellphones or computers, and then to the Internet for communication with centralized healthcare structures. There are, however, considerable challenges to be faced before PoC devices become routine in the clinical practice. For instance, the implementation of this technology requires integration of detection components with other fluid regulatory elements at the microscale, where fluid-flow properties become increasingly controlled by viscous forces rather than inertial forces. Another challenge is to develop new materials for environmentally friendly, cheap, and portable microfluidic devices. In this review paper, we first revisit the progress made in the last few years and discuss trends and strategies for the fabrication of microfluidic devices. Then, we discuss the challenges in lab-on-a-chip biosensing devices, including colorimetric sensors coupled to smartphones, plasmonic sensors, and electronic tongues. The latter ones use statistical and big data analysis for proper classification. The increasing use of big data and artificial intelligence methods is then commented upon in the context of wearable and handled biosensing platforms for the Internet of things and futuristic healthcare systems.

Assuntos