A systematic review was conducted to determine the trends in devices and parameters used for brain photobiomodulation (PBM). The revised studies included clinical and cadaveric approaches, in which light stimuli were applied to the head and/or neck. PubMed, Scopus, Web of Science and Google Scholar databases were used for the systematic search. A total of 2133 records were screened, from which 97 were included in this review. The parameters that were extracted and analysed in each article were the device design, actuation area, actuation site, wavelength, mode of operation, power density, energy density, power output, energy per session and treatment time. To organize device information, 11 categories of devices were defined, according to their characteristics. The most used category of devices was laser handpieces, which relate to 21% of all devices, while 28% of the devices were not described. Studies for cognitive function and physiological characterisation are the most well defined ones and with more tangible results. There is a lack of consistency when reporting PBM studies, with several articles under defining the stimulation protocol, and a wide variety of parameters used for the same health conditions (e.g., Alzheimer's or Parkinson's disease) resulting in positive outcomes. Standardization for the report of these studies is warranted, as well as sham-controlled comparative studies to determine which parameters have the greatest effect on PBM treatments for different neurological conditions.
Low-Level Light Therapy , Humans , Low-Level Light Therapy/methods , Brain , Cognition , Lasers
Among the adjunctive procedures to accelerate orthodontic tooth movement (OTM), ultrasound (US) is a nonsurgical form of mechanical stimulus that has been explored as an alternative to the currently available treatments. This study aimed to clarify the role of US in OTM by exploring different stimulation parameters and their effects on the biological responses of cells involved in OTM. Human fetal osteoblasts and periodontal ligament fibroblasts cell lines were stimulated with US at 1.0 and 1.5 MHz central frequencies and power densities of 30 and 60 mW/cm2 in continuous mode for 5 and 10 min. Cellular proliferation, metabolic activity and protein expression were analyzed. The US parameters that significantly improved the metabolic activity were 1.0 MHz at 30 mW/cm2 for 5 min and 1.0 MHz at 60 mW/cm2 for 5 and 10 min for osteoblasts; and 1.0 MHz at 30 mW/cm2 for 5 min and 1.5 MHz at 60 mW/cm2 for 5 and 10 min for fibroblasts. By stimulating with these parameters, the expression of alkaline phosphatase was maintained, while osteoprotegerin synthesis was induced after three days of US stimulation. The US stimulation improved the biological activity of both osteoblasts and periodontal ligament fibroblasts, inducing their osteogenic differentiation.
Numerous pieces of evidence have supported the therapeutic potential of photobiomodulation (PBM) to modulate bone remodeling on mechanically stimulated teeth, proving PBM's ability to be used as a coadjuvant treatment to accelerate orthodontic tooth movement (OTM). However, there are still uncertainty and discourse around the optimal PBM protocols, which hampers its optimal and consolidated clinical applicability. Given the differential expression and metabolic patterns exhibited in the tension and compression sides of orthodontically stressed teeth, it is plausible that different types of irradiation may be applied to each side of the teeth. In this sense, this study aimed to design and implement an optimization protocol to find the most appropriate PBM parameters to stimulate specific bone turnover processes. To this end, three levels of wavelength (655, 810 and 940 nm), two power densities (5 and 10 mW/cm2) and two regimens of single and multiple sessions within three consecutive days were tested. The biological response of osteoblasts and periodontal ligament (PDL) fibroblasts was addressed by monitoring the PBM's impact on the cellular metabolic activity, as well as on key bone remodeling mediators, including alkaline phosphatase (ALP), osteoprotegerin (OPG) and receptor activator of nuclear factor κ-B ligand (RANK-L), each day. The results suggest that daily irradiation of 655 nm delivered at 10 mW/cm2, as well as 810 and 940 nm light at 5 mW/cm2, lead to an increase in ALP and OPG, potentiating bone formation. In addition, irradiation of 810 nm at 5 mW/cm2 delivered for two consecutive days and suspended by the third day promotes a downregulation of OPG expression and a slight non-significant increase in RANK-L expression, being suitable to stimulate bone resorption. Future studies in animal models may clarify the impact of PBM on bone formation and resorption mediators for longer periods and address the possibility of testing different stimulation periodicities. The present in vitro study offers valuable insights into the effectiveness of specific PBM protocols to promote osteogenic and osteoclastogenesis responses and therefore its potential to stimulate bone formation on the tension side and bone resorption on the compression side of orthodontically stressed teeth.
OBJECTIVE: The aim of this study was to evaluate the influence of the thickness of resin-matrix composite blocks manufactured by CAD-CAM on the light transmittance towards different resin-matrix cements or flowable composites. METHODS: Sixty specimens of resin-matrix composite CAD-CAM blocks reinforced with 89 wt% inorganic fillers were cross-sectioned with 2 or 3 mm thicknesses. The specimens were conditioned with adhesive system and divided in groups according to the luting material, namely: two dual-cured resin-matrix cements, two traditional flowable resin-matrix composites, and one thermal-induced flowable resin-matrix composite. Specimens were light-cured at 900 mW/cm2 for 40s. Light transmittance assays were preformed using a spectrophotometer with an integrated monochromator before and after light-curing. Microstructural analysis was performed by optical and scanning electron microscopy (SEM). Nanoindentation tests were performed to evaluate mechanical properties for indirect evaluation of degree of monomers conversion. RESULTS: Optical and SEM images revealed low thickness values for the cementation interfaces for the traditional flowable resin-matrix composite. The cement thickness increased with the size and content of inorganic fillers. The highest light transmittance was recorded for the onlay blocks cemented with the traditional flowable resin-matrix composites while a group cemented with the dual-cured resin-matrix cement revealed the lowest light transmittance. The elastic modulus and hardness increased for specimens with high content of inorganic fillers as well as it increased in function of the light transmittance. CONCLUSIONS: The light transmittance of flowable resin-matrix composites was higher than that for resin-matrix cement after cementation to resin-matrix composites blocks. The type, size, and content of inorganic fillers of the luting material affected the thickness of the cement layer and light transmittance through the materials. CLINICAL RELEVANCE: On chair-side light curing, the transmission of visible light can be interfered by the chemical composition and viscosity of the luting materials. The increase in size and content of inorganic fillers of resin-matrix composites and luting materials can decrease the light transmittance leading to inefficient polymerization.
Composite Resins , Light-Curing of Dental Adhesives , Materials Testing , Surface Properties , Light-Curing of Dental Adhesives/methods , Composite Resins/chemistry , Resin Cements/chemistry
OBJECTIVES: The aim of this in vitro study was to evaluate the light transmission through five different resin-matrix composites regarding the inorganic filler content. METHODS: Resin-matrix composite disc-shaped specimens were prepared on glass molds. Three traditional resin-matrix composites contained inorganic fillers at 74, 80, and 89 wt. % while two flowable composites revealed 60 and 62.5 wt. % inorganic fillers. Light transmission through the resin-matrix composites was assessed using a spectrophotometer with an integrated monochromator before and after light curing for 10, 20, or 40s. Elastic modulus and nanohardness were evaluated through nanoindentation's tests, while Vicker's hardness was measured by micro-hardness assessment. Chemical analyses were performed by FTIR and EDS, while microstructural analysis was conducted by optical microscopy and scanning electron microscopy. Data were evaluated using two-way ANOVA and Tukey's test (p < 0.05). RESULTS: After polymerization, optical transmittance increased for all specimens above 650-nm wavelength irradiation since higher light exposure time leads to increased light transmittance. At 20- or 40-s irradiation, similar light transmittance was recorded for resin composites with 60, 62, 74, or 78-80 wt. % inorganic fillers. The lowest light transmittance was recorded for a resin-matrix composite reinforced with 89 wt. % inorganic fillers. Thus, the size of inorganic fillers ranged from nano- up to micro-scale dimensions and the high content of micro-scale inorganic particles can change the light pathway and decrease the light transmittance through the materials. At 850-nm wavelength, the average ratio between polymerized and non-polymerized specimens increased by 1.6 times for the resin composite with 89 wt. % fillers, while the composites with 60 wt. % fillers revealed an increased ratio by 3.5 times higher than that recorded at 600-nm wavelength. High mean values of elastic modulus, nano-hardness, and micro-hardness were recorded for the resin-matrix composites with the highest inorganic content. CONCLUSIONS: A high content of inorganic fillers at 89 wt.% decreased the light transmission through resin-matrix composites. However, certain types of fillers do not interfere on the light transmission, maintaining an optimal polymerization and the physical properties of the resin-matrix composites. CLINICAL SIGNIFICANCE: The type and content of inorganic fillers in the chemical composition of resin-matrix composites do affect their polymerization mode. As a consequence, the clinical performance of resin-matrix composites can be compromised, leading to variable physical properties and degradation.
Dentistry , Glass , Chromatography, Gas , Elastic Modulus , Hardness
Machine learning (ML) is a broad term encompassing several methods that allow us to learn from data. These methods may permit large real-world databases to be more rapidly translated to applications to inform patient-provider decision-making. This paper presents a review of articles that discuss the use of Fourier transform infrared (FTIR) spectroscopy and ML for human blood analysis between the years 2019-2023. The literature review was conducted to identify published research of employed ML linked with FTIR for distinction between pathological and healthy human blood cells. The articles' search strategy was implemented and studies meeting the eligibility criteria were evaluated. Relevant data related to the study design, statistical methods, and strengths and limitations were identified. A total of 39 publications in the last 5 years (2019-2023) were identified and evaluated for this review. Diverse methods, statistical packages, and approaches were used across the identified studies. The most common methods included support vector machine (SVM) and principal component analysis (PCA) approaches. Most studies applied internal validation and employed more than one algorithm, while only four studies applied one ML algorithm to the data. A wide variety of approaches, algorithms, statistical software, and validation strategies were employed in the application of ML methods. There is a need to ensure that multiple ML approaches are used, the model selection strategy is clearly defined, and both internal and external validation are necessary to be sure that the discrimination of human blood cells is being made with the highest efficient evidence.
OBJECTIVES: Optical spectrophotometry has been explored to quantify Plasmodium falciparum malaria parasites at low parasitemia, with potential to overcome the limitations of detection in the current diagnostic methods. This work presents the design, simulation and fabrication of a CMOS microelectronic detection system to automatically quantify the presence of malaria parasites in a blood sample. METHODS: The designed system is composed by an array of 16 n+/p-substrate silicon junction photodiodes as photodetectors and 16 current to frequency (IF) converters. An optical setup was used to individually and jointly characterize the entire system. RESULTS: The IF converter was simulated and characterized in Cadence Tools using UMC 1180 MM/RF technology rules, featuring a resolution of 0.01 nA, a linearity up to 1800 nA and a sensitivity of 4430 Hz/nA. After fabrication in a silicon foundry, the photodiodes' characterization presented a responsivity peak of 120 mA/W (λ = 570 nm) and a dark current of 7.15 pA at 0 V. Regarding the IF converter, it exhibited high linearity (R2 ≈ 0.999) up to 30 nA, with a sensitivity of 4840 Hz/nA. Furthermore, the microsystem performance was validated using RBCs (Red Blood Cells) infected with P. falciparum and diluted at different parasitemia (12, 25 and 50 parasites/µL). CONCLUSION: The microsystem was able to distinguish between healthy and infected RBCs, with a sensitivity of 4.5 Hz/parasites.µL-1. SIGNIFICANCE: The developed microsystem presents a competitive result, when compared to the gold standard diagnosis methods, with increased potential for malaria in field diagnosis.
Malaria, Falciparum , Malaria , Humans , Plasmodium falciparum , Silicon , Parasitemia/diagnosis , Parasitemia/parasitology , Malaria/diagnosis , Malaria, Falciparum/diagnosis , Malaria, Falciparum/parasitology , Spectrophotometry , Sensitivity and Specificity
In dentistry, clinicians mainly use dual-cured or light-cured resin-matrix cements to achieve a proper polymerization of the organic matrix leading to enhanced physical properties of the cement. However, several parameters can affect the polymerization of resin-matrix cements. The main aim of the present study was to perform a scoping review on the degree of conversion (DC) of the organic matrix, the polymerization, and the light transmittance of different resin-matrix cements used in dentistry. A search was performed on PubMed using a combination of the following key terms: degree of conversion, resin cements, light transmittance, polymerization, light curing, and thickness. Articles in the English language published up to November 2022 were selected. The selected studies' results demonstrated that restorative structures with a thickness higher than 1.5 mm decrease the light irradiance towards the resin-matrix cement. A decrease in light transmission provides a low energy absorption through the resin cement leading to a low DC percentage. On the other hand, the highest DC percentages, ranging between 55 and 75%, have been reported for dual-cured resin-matrix cements, although the polymerization mode and exposure time also influence the DC of monomers. Thus, the polymerization of resin-matrix cements can be optimized taking into account different parameters of light-curing, such as adequate light distance, irradiance, exposure time, equipment, and wavelength. Then, optimum physical properties are achieved that provide a long-term clinical performance of the cemented restorative materials.
Malaria is one of the most life-threatening infectious diseases worldwide, claiming half a million lives yearly. Prompt and accurate diagnosis is crucial for disease control and elimination. Currently used diagnostic methods require blood sampling and fail to detect low-level infections. At the symptomatic stage of infection, the parasites feed on red blood cells' (RBCs) hemoglobin, forming inert crystals, the hemozoin, in the process. Thus, along with parasite maturation inside the RBCs, the hemoglobin and hemozoin proportion is inversely related, and they generate specific optical spectra, according to their concentration. Herein, to address the issues of finger prick sampling and the lack of sensitivity of the parasitological test, we explored the optical features of Plasmodium falciparum-infected RBCs through absorbance and reflectance spectrophotometric characterization, aiming for their detection. This is the first work fully characterizing the spectrophotometric properties of P. falciparum-infected RBCs by using only 16 specific wavelengths within the visible optical spectra and two different post-processing algorithms. With such an innovative methodology, low-level infections can be detected and quantified, and early- and late-stage development can be clearly distinguished, not only improving the current detection limits but also proving the successful applicability of spectrophotometry for competitive and accurate malaria diagnosis.
Malaria, Falciparum , Malaria , Parasites , Animals , Plasmodium falciparum , Malaria, Falciparum/diagnosis , Malaria, Falciparum/parasitology , Malaria/parasitology , Spectrophotometry
The purpose of this systematic review is to analyze the methodologies, utilized stimulation parameters, and the main cellular outcomes obtained by in vitro studies that apply a light source on tenocyte cultures. Methods: The PubMed, Scopus, and Web of Science databases were searched up to December 9, 2019 for in vitro studies that used light sources on tenocyte cultures. A 13-item checklist was used to assess methodological quality of the studies and the risk of bias was assessed using the Risk of Bias Assessment tool for Non-randomized Studies tool. Results: Six studies were included. Tenocytes from the Achilles tendon were used by 83.3% of the studies, with 16.7% utilizing the deep digital flexor tendon, with cells in passage 2 to 5. Four studies used lasers and the other 2 used light-emitting diode or intense pulsed light, in wavelengths ranges from 530 to 1100 nm. The application of light to tenocytes resulted in positive effects reported by all studies, including an increase in cell proliferation and migration, and higher protein and gene expression of tendon biomarkers. Studies presented a lack of standardization on reporting light stimulation parameters and experimental methodologies, leading to low methodological quality. There was a high risk of selection, performance, detection, and reporting bias. Conclusions: All studies showed positive effects after light stimulation on tenocytes, regardless of the light source used. However, the lack of standardized data on light stimulation parameters, experimental setup, and the studies' main limitations hindered representative conclusions and comparisons amongst studies' main outcomes.
The efficient separation of blood components using microfluidic systems can help to improve the detection and diagnosis of several diseases, such as malaria and diabetes. Therefore, a novel multi-step microfluidic device, based on passive crossflow filters was developed. Three different designs were proposed, fabricated and tested in order to evaluate the most suitable geometry to perform, simultaneously, blood cells separation and cell deformability measurements. All the proposed geometries include a main channel and three sequential separation steps, all comprised of symmetrical crossflow filters, with multiple rows of pillars, to reduce the amount of red blood cells (RBCs) flowing to the outlets of the microfluidic device (MD). Sets of hyperbolic constrictions located at the outlets allow the assessment of cells deformability. Based on the proposed geometries, the three correspondent MD were evaluated and compared, by measuring the RBCs velocities, the cell-free layer (CFL) effect through the microchannels and by quantifying the amount of RBCs at the outlets. The results suggest that the proposed MD 3 configuration was the most effective one for the desired application, due to the formation of a wider CFL. As a result, a minor amount of RBCs flow through the hyperbolic contraction at the third separation level of the device. Nevertheless, for all the proposed geometries, the existence of three separation levels shows that it is possible to achieve a highly efficient cell separation. If needed, such microdevices have the potential for further improvements by increasing the number of separation levels, aiming the total separation of blood cells from plasma.
Lab-On-A-Chip Devices , Microfluidic Analytical Techniques , Cell Separation , Erythrocyte Count , Erythrocyte Deformability , Erythrocytes
Since microorganisms are evolving rapidly, there is a growing need for a new, fast, and precise technique to analyse blood samples and distinguish healthy from pathological samples. Fourier Transform Infrared (FTIR) spectroscopy can provide information related to the biochemical composition and how it changes when a pathological state arises. FTIR spectroscopy has undergone rapid development over the last decades with a promise of easier, faster, and more impartial diagnoses within the biomedical field. However, thus far only a limited number of studies have addressed the use of FTIR spectroscopy in this field. This paper describes the main concepts related to FTIR and presents the latest research focusing on FTIR spectroscopy technology and its integration in lab-on-a-chip devices and their applications in the biological field. This review presents the potential use of FTIR to distinguish between healthy and pathological samples, with examples of early cancer detection, human immunodeficiency virus (HIV) detection, and routine blood analysis, among others. Finally, the study also reflects on the features of FTIR technology that can be applied in a lab-on-a-chip format and further developed for small healthcare devices that can be used for point-of-care monitoring purposes. To the best of the authors' knowledge, no other published study has reviewed these topics. Therefore, this analysis and its results will fill this research gap.
The development of micro- and nanodevices for blood analysis continues to be a growing interdisciplinary subject that demands the careful integration of different research fields [...].
Despite being preventable and treatable, malaria still puts almost half of the world's population at risk. Thus, prompt, accurate and sensitive malaria diagnosis is crucial for disease control and elimination. Optical microscopy and immuno-rapid tests are the standard malaria diagnostic methods in the field. However, these are time-consuming and fail to detect low-level parasitemia. Biosensors and lab-on-a-chip devices, as reported to different applications, usually offer high sensitivity, specificity, and ease of use at the point of care. Thus, these can be explored as an alternative for malaria diagnosis. Alongside malaria infection inside the human red blood cells, parasites consume host hemoglobin generating the hemozoin crystal as a by-product. Hemozoin is produced in all parasite species either in symptomatic and asymptomatic individuals. Furthermore, hemozoin crystals are produced as the parasites invade the red blood cells and their content relates to disease progression. Hemozoin is, therefore, a unique indicator of infection, being used as a malaria biomarker. Herein, the so-far developed biosensors and lab-on-a-chip devices aiming for malaria detection by targeting hemozoin as a biomarker are reviewed and discussed to fulfil all the medical demands for malaria management towards elimination.
Hemeproteins , Malaria , Biomarkers , Erythrocytes/parasitology , Erythrocytes/physiology , Hemeproteins/metabolism , Humans , Malaria/blood , Malaria/diagnosis , Malaria/parasitology
Early and effective malaria diagnosis is vital to control the disease spread and to prevent the emergence of severe cases and death. Currently, malaria diagnosis relies on optical microscopy and immuno-rapid tests; however, these require a drop of blood, are time-consuming, or are not specific and sensitive enough for reliable detection of low-level parasitaemia. Thus, there is an urge for simpler, prompt, and accurate alternative diagnostic methods. Particularly, hemozoin has been increasingly recognized as an attractive biomarker for malaria detection. As the disease proliferates, parasites digest host hemoglobin, in the process releasing toxic haem that is detoxified into an insoluble crystal, the hemozoin, which accumulates along with infection progression. Given its magnetic, optical, and acoustic unique features, hemozoin has been explored for new label-free diagnostic methods. Thereby, herein, we review the hemozoin-based malaria detection methods and critically discuss their challenges and potential for the development of an ideal diagnostic device.
Hemeproteins , Malaria , Heme , Humans , Malaria/diagnosis , Microscopy
Malaria diagnosis relies on optical microscopy and/or rapid diagnostic tests based on detecting specific malaria antigens. The clinical sensitivity of these methods is highly dependent on parasite density, with low levels of detection at low parasite density, challenging the worldwide malaria elimination efforts. Therefore, there is a need for diagnostic methods with higher sensitivity, demanding innovative diagnostics devices able to detect malaria at low parasite density and at early stages of the disease. We propose an innovative optical device for malaria diagnosis, based on optical reflectance spectrophotometry, for the detection of parasites through the quantification of haemozoin. For this purpose, a set of eight thin-film optical filters, based on multilayer stacks of MgO/TiO2 and SiO2/TiO2 thin-films, with high transmittance and low full width at half maximum (FWHM) at specific wavelengths, was designed and fully characterized (both numerically and experimentally). A preliminary assessment of its potential to reconstruct the original spectra of red blood cells was performed, both in uninfected and Plasmodium falciparum-infected samples. The obtained results show that, although the experimental filters have a non-ideal performance characteristic, they allow us to distinguish, based on only 8 discrete points in the optical spectrum, between healthy and malaria infected samples, up to a detection limit of 12 parasites/µL of red blood cells. Those results enhance the potential of using such a device for malaria diagnostics, aiming for non-invasiveness.
OBJECTIVE: This paper focuses on a novel and portable device prototype with optical detectors to quickly and efficiently detect hemozoin (Hz) in blood, aiming at malaria diagnostics. METHODS: Taking advantage of the particular features of malaria parasite in infected blood, particularly the Hz formation, the main innovation described is a portable device for the optical quantification of parasitic Hz in blood, through optical absorbance spectrophotometry. This device comprises detection chambers for fluidic samples, an optical emission and detection system, and a power supply system to provide autonomy. The working principle is based on colorimetric detection, by absorbance, at six specific wavelengths. A detection algorithm relates the absorbance values at all wavelengths to quantify the Hz concentration, thus working as a biomarker of malaria presence and stage. RESULTS: Under the tested conditions, e.g., in fluidic samples containing synthetic Hz, hemoglobin, and diluted whole blood, the device detected Hz above 1 µg/mL concentrations with 100% sensitivity and 96.3% specificity. CONCLUSION: This paper features an autonomous, portable, 1-min analysis time, and low-cost per test device, without the need for samples, centrifugation, allowing the use of whole blood. SIGNIFICANCE: The presented device is a step ahead for meeting the growing clinical demands for reliable, rapid, portable, and quantitative malaria diagnosis.
Blood Chemical Analysis/instrumentation , Hemeproteins/analysis , Malaria/diagnosis , Spectrophotometry/instrumentation , Algorithms , Equipment Design , Erythrocytes/chemistry , Humans , Point-of-Care Testing
The development of microdevices for blood analysis is an interdisciplinary subject that demands an integration of several research fields such as biotechnology, medicine, chemistry, informatics, optics, electronics, mechanics, and micro/nanotechnologies [...].
Since the first microfluidic device was developed more than three decades ago, microfluidics is seen as a technology that exhibits unique features to provide a significant change in the way that modern biology is performed. Blood and blood cells are recognized as important biomarkers of many diseases. Taken advantage of microfluidics assets, changes on blood cell physicochemical properties can be used for fast and accurate clinical diagnosis. In this review, an overview of the microfabrication techniques is given, especially for biomedical applications, as well as a synopsis of some design considerations regarding microfluidic devices. The blood cells separation and sorting techniques were also reviewed, highlighting the main achievements and breakthroughs in the last decades.
