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Antennas that can operate across multiple communication standards have remained a challenge. To address these limitations, we propose a Field-Programmable Radio Frequency Surface (FPRFS), which is based on manipulating current flow on its surface to achieve desirable RF characteristics. In this work, we demonstrate that substantial enhancements in radiation efficiency can be achieved while preserving the high reconfigurability of antenna structures implemented on the FPRFS. This is accomplished by utilizing an asymmetric excitation, directing the excitation to the low-loss contiguous surface, and dynamically manipulating the imaged return current on a segmented ground plane by switches. This important insight allows for adaptable antenna performance that weakly depends on the number of RF switches or their loss. We experimentally validate that FPRFS antennas can achieve efficiencies comparable to traditionally implemented antenna counterparts. This permits the FPRFS to be effectively utilized as a productive antenna and impedance-matching network with real-time reconfigurability.
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Reverse transcription loop-mediated isothermal amplification (RT-LAMP) is a molecular amplification method that can detect SARS-CoV-2 in a shorter time than the current gold-standard molecular diagnostic reverse transcription-polymerase chain reaction (RT-PCR). However, previously developed RT-LAMP assays have mostly relied on highly subjective visual colorimetric interpretation. In this study, an RT-LAMP assay was developed with quantitative measurement of reaction pH using a novel portable pH biosensor compared to qualitative colorimetric interpretation and gel electrophoresis, with 57 clinical COVID-19 samples used for validation of the test. The LoD of the assay is 103 copies/µL. The highest sensitivity was found in the qualitative methods (93.75%), while the highest specificity and likelihood ratio was found in the pH sensor (87.5% and 6.72). On the sensor measurement, a significant difference (p < 0.0001) was observed between the average pH of the RT-PCR (+) COVID-19 (6.15 ± 0.27), while the average pH of the RT-PCR (-) samples (6.72 ± 0.22). Correlation analysis revealed a strong correlation (r = 0.78, p < 0.0001) between the Ct values obtained from RT-PCR with the biosensor pH readout. RT-LAMP with the quantitative pH sensor readout method has the potential to be further developed as an objective molecular assay for rapid and simple detection of SARS-CoV-2.
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Técnicas Biosensibles , COVID-19 , Técnicas de Amplificación de Ácido Nucleico , SARS-CoV-2 , Sensibilidad y Especificidad , Humanos , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Técnicas de Amplificación de Ácido Nucleico/métodos , Concentración de Iones de Hidrógeno , COVID-19/diagnóstico , COVID-19/virología , Técnicas Biosensibles/métodos , Técnicas de Diagnóstico Molecular/métodos , Colorimetría/métodos , Prueba de Ácido Nucleico para COVID-19/métodos , ARN Viral/genética , ARN Viral/análisis , Límite de DetecciónRESUMEN
OBJECTIVES: Older adults have an elevated risk of dehydration, a state with proven detrimental cognitive and physical effects. Furthermore, the use of diuretics by hypertensive patients further compounds this risk. This prospective study investigated the diagnostic accuracy of point-of-care (POC) salivary osmolarity (SOSM) measurement for the detection of dehydration in hypertensive adults with and without diuretic pharmacotherapy. DESIGN: Prospective diagnostic accuracy study. SETTING: Home visits to patients recruited from 4 community health centers in West Sulawesi, Indonesia. PARTICIPANTS: A total of 148 hypertensive older adults (57 men, 91 women). The mean ages of male and female patients were 69.4 ± 11.4 and 68.1 ± 7.8 years, respectively. METHODS: Hypertensive adults were divided into 2 groups based on the presence of diuretics in their pharmacotherapeutic regimen. First-morning mid-stream urine samples were used to perform urine specific gravity (USG) testing. Same-day SOSM measurements were obtained using a POC saliva testing system. RESULTS: Both USG (P = .0002) and SOSM (P < .0001) were significantly elevated in hypertensive patients with diuretic pharmacotherapy. At a USG threshold of ≥1.030, 86% of diuretic users were classified as dehydrated compared with 55% of non-using participants. A strong correlation was observed between USG and SOSM measurements (r = 0.78, P < .0001). Using a USG threshold of ≥1.030 as a hydration classifier, an SOSM threshold of ≥93 mOsm had a sensitivity of 78.6% and a specificity of 91.1% for detecting dehydration. CONCLUSIONS AND IMPLICATIONS: Hypertensive patients on diuretics have significantly higher first-morning USG and SOSM values, indicating a higher likelihood of dehydration relative to those on other classes of antihypertensive medication. POC SOSM assessment correlates strongly with first-morning USG assessment, and represents a rapid and noninvasive alternative to urinary hydration assessment that may be applicable for routine use in populations with elevated risk of dehydration.
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Hipertensión , Sistemas de Atención de Punto , Humanos , Femenino , Masculino , Anciano , Persona de Mediana Edad , Anciano de 80 o más Años , Estudios Prospectivos , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológicoRESUMEN
BACKGROUND: Brain structural alterations and cognitive dysfunction are independent predictors for poor clinical outcome in schizophrenia, and the associations between these domains remains unclear. We employed a novel, multiblock partial least squares correlation (MB-PLS-C) technique and investigated multivariate cortico-cognitive patterns in patients with treatment-resistant schizophrenia (TRS) and matched healthy controls (HC). METHOD: Forty-one TRS patients (age 38.5 ± 9.1, 30 males (M)), and 45 HC (age 40.2 ± 10.6, 29 M) underwent 3T structural MRI. Volumes of 68 brain regions and seven variables from CANTAB covering memory and executive domains were included. Univariate group differences were assessed, followed by the MB-PLS-C analyses to identify group-specific multivariate patterns of cortico-cognitive coupling. Supplementary three-group analyses, which included 23 non-affected first-degree relatives (NAR), were also conducted. RESULTS: Univariate tests demonstrated that TRS patients showed impairments in all seven cognitive tasks and volume reductions in 12 cortical regions following Bonferroni correction. The MB-PLS-C analyses revealed two significant latent variables (LVs) explaining > 90% of the sum-of-squares variance. LV1 explained 78.86% of the sum-of-squares variance, describing a shared, widespread structure-cognitive pattern relevant to both TRS patients and HCs. In contrast, LV2 (13.47% of sum-of-squares variance explained) appeared specific to TRS and comprised a differential cortico-cognitive pattern including frontal and temporal lobes as well as paired associates learning (PAL) and intra-extra dimensional set shifting (IED). Three-group analyses also identified two significant LVs, with NARs more closely resembling healthy controls than TRS patients. CONCLUSIONS: MB-PLS-C analyses identified multivariate brain structural-cognitive patterns in the latent space that may provide a TRS signature.
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Trastornos del Conocimiento , Esquizofrenia , Cognición , Trastornos del Conocimiento/psicología , Humanos , Masculino , Pruebas Neuropsicológicas , Esquizofrenia Resistente al TratamientoRESUMEN
Acute stroke is the third leading cause of mortality and disability worldwide. Administration of appropriate therapy for acute stroke is critically dependent on timely classification into either ischemic or hemorrhagic subtypes, which have divergent treatment pathways. The current classification method is based on neuroimaging, which generally requires the transport of the patient to a hospital-based facility unless a mobile stroke unit is available. Plasma glial fibrillary acidic protein (GFAP) level has been identified as a useful blood-based biomarker to differentiate stroke subtypes. However, its conventional immunoassay methods are laboratory-based and time-consuming. Novel approaches for rapid stroke classification near the patients are urgently needed. Here, we report the development and testing of a microfluidic-based magnetoimpedance biosensor platform for measuring GFAP levels. The platform consists of a microfluidic chip for GFAP extraction from a blood sample and a magnetoimpedance (MI) biosensor that employs Dynabeads as a magnetic label to capture the GFAP molecules. We demonstrated the detection of recombinant GFAP protein in phosphate-buffered saline (PBS) and in mouse blood samples (detection limit 0.01 ng/mL) and of physiological GFAP in blood and plasma samples (detection limit 1.0 ng/mL) obtained from acute stroke patients. This detection level is within the range of cut-off levels required for clinical stroke subtype differentiation. This platform has the potential to be incorporated into a small device with further development to assist in the classification of acute stroke patients and clinical decision-making at the point-of-care.
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Técnicas Biosensibles , Isquemia Encefálica , Accidente Cerebrovascular , Animales , Biomarcadores , Isquemia Encefálica/diagnóstico , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/terapia , Proteína Ácida Fibrilar de la Glía , Humanos , Ratones , Microfluídica , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapiaRESUMEN
The magnetic beads detection-based immunoassay, also called magneto-immunoassay, has potential applications in point-of-care testing (POCT) due to its unique advantage of minimal background interference from the biological sample and associated reagents. While magnetic field detection technologies are well established for numerous applications in the military, as well as in geology, archaeology, mining, spacecraft, and mobile phones, adaptation into magneto-immunoassay is yet to be explored. The magnetic field biosensors under development tend to be multilayered and require an expensive fabrication process. A low-cost and affordable biosensing platform is required for an effective point-of-care diagnosis in a resource-limited environment. Therefore, we evaluated a single-layered magnetic biosensor in this study to overcome this limitation. The shape-induced magnetic anisotropy-based planar hall effect sensor was recently developed to detect a low-level magnetic field, but was not explored for medical application. In this study, the elliptical-shaped planar hall effect (EPHE) sensor was designed, fabricated, characterized, and optimized for the magneto-immunoassay, specifically. Nine sensor variants were designed and fabricated. A customized measurement setup incorporating a lock-in amplifier was used to quantify 4.5 µm magnetic beads in a droplet. The result indicated that the single-domain behaviour of the magnetic film and larger sensing area with a thinner magnetic film had the highest sensitivity. The developed sensor was tested with a range of magnetic bead concentrations, demonstrating a limit of detection of 200 beads/µL. The sensor performance encourages employing magneto-immunoassay towards developing a low-cost POCT device in the future.
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Técnicas Biosensibles , Técnicas Biosensibles/instrumentación , Diseño de Equipo , Inmunoensayo/instrumentación , Separación Inmunomagnética , MagnetismoRESUMEN
Thin-film magneto-impedance (MI) biosensors have attracted significant attention due to their high sensitivity and easy miniaturization. However, further improvement is required to detect weak biomagnetic signals. Here, we report a meander thin-film biosensor preparation to investigate the fabrication parameters influencing the MI effect. Specifically, we hypothesized that an optimal film thickness and sensing area size ratio could be achieved to obtain a maximum MI ratio. A meander multilayer MI biosensor based on a NiFe/Cu/NiFe thin-film was designed and fabricated into 3-, 6-, and 9-turn models with film thicknesses of 3 µm and 6 µm. The 9-turn biosensor resembled the largest sensing area, while the 3- and 6-turn biosensors were designed with identical sensing areas. The results indicated that the NiFe film thickness of 6 µm with a sensing area size of 14.4 mm2 resembling a 9-turn MI biosensor is the optimal ratio yielding the maximum MI ratio of 238%, which is 70% larger than the 3- and 6-turn structures. The 3- and 6-turn MI biosensors exhibited similar characteristics where the MI ratio peaked at a similar value. Our results suggest that the MI ratio can be increased by increasing the sensing area size and film thickness rather than the number of turns. We showed that an optimal film thickness to sensing area size ratio is required to obtain a high MI ratio. Our findings will be useful for designing highly sensitive MI biosensors capable of detecting low biomagnetic signals.
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Técnicas Biosensibles , Impedancia EléctricaRESUMEN
HLA-B*15:02 screening before administering carbamazepine is recommended to prevent life-threatening hypersensitivity. However, the unavailability of a point-of-care device impedes this screening process. Our research group previously developed a two-step HLA-B*15:02 detection technique utilizing loop-mediated isothermal amplification (LAMP) on the tube, which requires two-stage device development to translate into a portable platform. Here, we report a heater-integrated lab-on-a-chip device for the LAMP amplification, which can rapidly detect HLA-B alleles colorimetrically. A gold-patterned micro-sized heater was integrated into a 3D-printed chip, allowing microfluidic pumping, valving, and incubation. The performance of the chip was tested with color dye. Then LAMP assay was conducted with human genomic DNA samples of known HLA-B genotypes in the LAMP-chip parallel with the tube assay. The LAMP-on-chip results showed a complete match with the LAMP-on-tube assay, demonstrating the detection system's concurrence.
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Hipersensibilidad a las Drogas , Antígenos HLA-B , Dispositivos Laboratorio en un Chip , Alelos , Humanos , Técnicas de Diagnóstico Molecular , Técnicas de Amplificación de Ácido NucleicoRESUMEN
BACKGROUND: Coronavirus disease 2019 has highlighted deficiencies in the testing capacity of many developed countries during the early stages of pandemics. Here we describe a strategy using pan-family viral assays to improve early accessibility of large-scale nucleic acid testing. METHODS: Coronaviruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were used as a case study for assessing utility of pan-family viral assays during the early stages of a novel pandemic. Specificity of a pan-coronavirus (Pan-CoV) assay for a novel pathogen was assessed using the frequency of common human coronavirus (HCoV) species in key populations. A reported Pan-CoV assay was assessed to determine sensitivity to 60 reference coronaviruses, including SARS-CoV-2. The resilience of the primer target regions of this assay to mutation was assessed in 8893 high-quality SARS-CoV-2 genomes to predict ongoing utility during pandemic progression. RESULTS: Because of common HCoV species, a Pan-CoV assay would return false positives for as few as 1% of asymptomatic adults, but up to 30% of immunocompromised patients with respiratory disease. One-half of reported Pan-CoV assays identify SARS-CoV-2 and with small adjustments can accommodate diverse variation observed in animal coronaviruses. The target region of 1 well-established Pan-CoV assay is highly resistant to mutation compared to species-specific SARS-CoV-2 reverse transcriptase-polymerase chain reaction assays. CONCLUSIONS: Despite cross-reactivity with common pathogens, pan-family assays may greatly assist management of emerging pandemics through prioritization of high-resolution testing or isolation measures. Targeting highly conserved genomic regions make pan-family assays robust and resilient to mutation. A strategic stockpile of pan-family assays may improve containment of novel diseases before the availability of species-specific assays.
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COVID-19 , Pandemias , Animales , Humanos , Tamizaje Masivo , Salud Pública , SARS-CoV-2RESUMEN
AIM: Voluntary dehydration, or lack of fluid intake despite water availability, is common in otherwise healthy children, and can lead to adverse effects. Most dehydration biomarkers are impractical for routine assessment in paediatric populations. This study aimed to assess two non-invasive hydration assessment tools, urine specific gravity (USG ) and a novel point-of-care (POC) salivary osmolarity (SOSM) sensor, in healthy children. METHODS: Volunteers were tested by colorimetric USG and a handheld SOSM system. Observed values were compared against previous studies to determine hydration status, as was the concordance between parameters. RESULTS: At the common USG threshold of 1.020, 42.4% of the 139 healthy children were dehydrated. The same prevalence was found using the 70-mOSM cut-off value. Comparative analysis of SOSM at varying USG thresholds demonstrated significantly higher SOSM in dehydrated children with a USG ≥ 1.030 (P = 0.002). CONCLUSION: At the USG threshold of 1.020 and SOSM threshold of 70 mOSM, 42.4% of healthy children were found to be voluntarily dehydrated. Significantly higher SOSM was observed in dehydrated children (USG ≥ 1.030). As the first study on the utility of POC SOSM measurements for detecting dehydration, these results provide a foundation for future POC characterisation of SOSM in other populations and clinical contexts.
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Deshidratación , Saliva , Niño , Deshidratación/diagnóstico , Humanos , Concentración Osmolar , Sistemas de Atención de Punto , Urinálisis , OrinaRESUMEN
Biosensors based on magneto-impedance (MI) effect are powerful tools for biomedical applications as they are highly sensitive, stable, exhibit fast response, small in size, and have low hysteresis and power consumption. However, the performance of these biosensors is influenced by a variety of factors, including the design, geometry, materials and fabrication procedures. Other less appreciated factors influencing the MI effect include measuring circuit implementation, the material used for construction, geometry of the thin film sensing element, and patterning shapes compatible with the interface microelectronic circuitry. The type magnetic (ferrofluid, Dynabeads, and nanoparticles) and size of the particles, the magnetic particle concentration, magnetic field strength and stray magnetic fields can also affect the sensor sensitivity. Based on these considerations it is proposed that ideal MI biosensor sensitivity could be achieved when the sensor is constructed in sandwich thick magnetic layers with large sensing area in a meander shape, measured with circuitry that provides the lowest possible external inductance at high frequencies, enclosed by a protective layer between magnetic particles and sensing element, and perpendicularly magnetized when detecting high-concentration of magnetic particles.
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Técnicas Biosensibles , Nanopartículas , Impedancia Eléctrica , Campos Magnéticos , MagnetismoRESUMEN
Human Leucocyte Antigen (HLA) testing is useful in the clinical work-up of coeliac disease (CD) with high negative but low positive predictive value. We construct a genomic risk score (GRS) using HLA risk genotypes to improve CD prediction and guide exclusion criteria. Imputed HLA genotypes for five European CD case-control GWAS (n > 15,000) were used to construct and validate an interpretable HLA-based risk model (HDQ15), which shows statistically significant improvements in predictive performance upon all previous HLA-based risk models. Conditioning on this model, we find two novel associations, HLA-DQ6.2 and HLA-DQ7.3, that interact significantly with HLA-DQ2.5 (p = 2.51 × 10-9, 1.99 × 10-7, respectively). Integrating these novel alleles into a new risk model (HDQ17) leads to predictive performance equivalent or better than the strongest reported GRS (GRS228) using 228 single nucleotide polymorphisms (SNPs). We also demonstrate that our proposed HLA-based models can be implemented using only six HLA tagging SNPs with statistically equivalent predictive performance. Using insights from our model to guide exclusionary criteria, we find the positive predictive value of CD testing in high-risk populations can be increased by 55%, from 17.5 to 27.1%, while maintaining a negative predictive value above 99%. Our results suggest that HLA typing is currently undervalued in CD assessment.
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Enfermedad Celíaca/genética , Epistasis Genética , Estudio de Asociación del Genoma Completo/métodos , Antígenos HLA/genética , Algoritmos , Alelos , Antígenos HLA/metabolismo , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
Schizotypal disorder lies in the schizophrenia spectrum and is widely studied in adult populations. Schizotypal disorder in children (SDc) is less well described. This study examined brain morphological and functional connectivity abnormalities in SDc (12 SDc and 9 typically developing children), focusing on the default mode and executive control brain networks. Results indicated that SDc is associated with reduced grey matter volume (GMV) in superior and medial frontal gyri, and increased resting-state functional connectivity between the superior frontal gyrus and inferior parietal lobule, compared to typically developing children (cluster-level FWE-corrected p < 0.05). The brain structure abnormality (GMV in left superior frontal gyrus) was correlated with clinical symptoms in SDc (r = -0.66, p = 0.026) and functional connectivity abnormality was correlated with extra-dimensional shifting impairments in all participants (r = 0.62, p = 0.011), suggesting their contribution to the underlying mechanisms of clinical presentation. These preliminary results motivate further work to characterize the neural basis of SDc and its significance as a risk factor for later psychosis.
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To function, mobile phone systems require transmitters that emit and receive radiofrequency signals over an extended geographical area exposing humans in all stages of development ranging from in-utero, early childhood, adolescents and adults. This study evaluates the question of the impact of radiofrequency radiation on living organisms in vitro studies. In this study, we abstract data from 300 peer-reviewed scientific publications (1990-2015) describing 1127 experimental observations in cell-based in vitro models. Our first analysis of these data found that out of 746 human cell experiments, 45.3% indicated cell changes, whereas 54.7% indicated no changes (p = 0.001). Realizing that there are profound distinctions between cell types in terms of age, rate of proliferation and apoptosis, and other characteristics and that RF signals can be characterized in terms of polarity, information content, frequency, Specific Absorption Rate (SAR) and power, we further refined our analysis to determine if there were some distinct properties of negative and positive findings associated with these specific characteristics. We further analyzed the data taking into account the cumulative effect (SAR × exposure time) to acquire the cumulative energy absorption of experiments due to radiofrequency exposure, which we believe, has not been fully considered previously. When the frequency of signals, length and type of exposure, and maturity, rate of growth (doubling time), apoptosis and other properties of individual cell types are considered, our results identify a number of potential non-thermal effects of radiofrequency fields that are restricted to a subset of specific faster-growing less differentiated cell types such as human spermatozoa (based on 19 reported experiments, p-value = 0.002) and human epithelial cells (based on 89 reported experiments, p-value < 0.0001). In contrast, for mature, differentiated adult cells of Glia (p = 0.001) and Glioblastoma (p < 0.0001) and adult human blood lymphocytes (p < 0.0001) there are no statistically significant differences for these more slowly reproducing cell lines. Thus, we show that RF induces significant changes in human cells (45.3%), and in faster-growing rat/mouse cell dataset (47.3%). In parallel with this finding, further analysis of faster-growing cells from other species (chicken, rabbit, pig, frog, snail) indicates that most undergo significant changes (74.4%) when exposed to RF. This study confirms observations from the REFLEX project, Belyaev and others that cellular response varies with signal properties. We concur that differentiation of cell type thus constitutes a critical piece of information and should be useful as a reference for many researchers planning additional studies. Sponsorship bias is also a factor that we did not take into account in this analysis.
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Teléfono Celular , Desarrollo Embrionario , Exposición a la Radiación , Adolescente , Animales , Línea Celular , Niño , Preescolar , Campos Electromagnéticos , Desarrollo Embrionario/efectos de la radiación , Humanos , Masculino , Ratones , Conejos , Exposición a la Radiación/efectos adversos , Ondas de Radio/efectos adversos , Ratas , PorcinosRESUMEN
Thermoelectric devices have great potential as a sustainable energy conversion technology to harvest waste heat and perform spot cooling with high reliability. However, most of the thermoelectric devices use toxic and expensive materials, which limits their application. These materials also require high-temperature fabrication processes, limiting their compatibility with flexible, bio-compatible substrate. Printing electronics is an exciting new technique for fabrication that has enabled a wide array of biocompatible and conformable systems. Being able to print thermoelectric devices allows them to be custom made with much lower cost for their specific application. Significant effort has been directed toward utilizing polymers and other bio-friendly materials for low-cost, lightweight, and flexible thermoelectric devices. Fortunately, many of these materials can be printed using low-temperature printing processes, enabling their fabrication on biocompatible substrates. This review aims to report the recent progress in developing high performance thermoelectric inks for various printing techniques. In addition to the usual thermoelectric performance measures, we also consider the attributes of flexibility and the processing temperatures. Finally, recent advancement of printed device structures is discussed which aims to maximize the temperature difference across the junctions.
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In this paper, we propose a scalable approach toward all-printed high-performance metal oxide thin-film transistors (TFTs), using a high-resolution electrohydrodynamic (EHD) printing process. Direct EHD micropatterning of metal oxide TFTs is based on diverse precursor solutions to form semiconducting materials (In2O3, In-Ga-ZnO (IGZO)), conductive metal oxide (Sn-doped In2O3 (ITO)), as well as aluminum oxide (Al2O3) gate dielectric at low temperatures. The fully printed TFT devices exhibit excellent electron transport characteristics (average electron mobilities of up to 117 cm2 V-1 s-1), negligible hysteresis, excellent uniformity, and stable operation at low-operating voltage. Furthermore, integrated logic gates such as NOT and NAND have been printed and demonstrated. All-printed logic with individual gating and symmetric input/output behavior, which is crucial for large-scale integration, is also demonstrated. The devices and fabrication process described in this paper enable high-performance and high-reliability transparent electronics.
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Malaria elimination is a global public health priority. To fulfil the demands of elimination diagnostics, we have developed an interdigitated electrode sensor platform targeting the Plasmodium falciparum Histidine Rich Protein 2 (PfHRP2) protein in saliva samples. A protocol for frequency-specific PfHRP2 detection in phosphate buffered saline was developed, yielding a sensitivity of 2.5 pg/mL based on change in impedance magnitude of the sensor. This protocol was adapted and optimized for use in saliva with a sensitivity of 25 pg/mL based on change in resistance. Further validation demonstrated detection in saliva spiked with PfHRP2 from clinical isolates in 8 of 11 samples. With a turnaround time of ~2 hours, the label-free platform based on impedance sensors has the potential for miniaturization into a point-of-care diagnostic device for malaria elimination.
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Antígenos de Protozoos/análisis , Malaria Falciparum/diagnóstico , Plasmodium falciparum/metabolismo , Proteínas Protozoarias/análisis , Saliva/parasitología , Técnicas Biosensibles/instrumentación , Pruebas Diagnósticas de Rutina , Impedancia Eléctrica , Humanos , Miniaturización , Sistemas de Atención de Punto , Sensibilidad y EspecificidadRESUMEN
Pre-treatment screening of individuals for human leukocyte antigens (HLA) HLA-B*57:01 is recommended for the prevention of life-threatening hypersensitivity reactions to abacavir, a drug widely prescribed for HIV treatment. However, the implementation of screening in clinical practice is hindered by the slow turnaround time and high cost of conventional HLA genotyping methods. We have developed a biosensor platform using interdigitated electrode (IDE) functionalized with a monoclonal antibody to detect cells expressing HLA-B*57:01. This platform was evaluated using cell lines and peripheral blood mononuclear cells expressing different HLA-B alleles. The functionalized IDE sensor was able to specifically capture HLA-B*57:01 cells, resulting in a significant change in the impedance magnitude in 20 min. This IDE platform has the potential to be further developed to enable point-of-care HLA-B*57:01 screening.
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Técnicas Biosensibles/métodos , Didesoxinucleósidos/efectos adversos , Hipersensibilidad a las Drogas/prevención & control , Antígenos HLA-B/análisis , Leucocitos Mononucleares/metabolismo , Alelos , Anticuerpos Inmovilizados/química , Anticuerpos Inmovilizados/inmunología , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/inmunología , Didesoxinucleósidos/uso terapéutico , Hipersensibilidad a las Drogas/etiología , Técnicas Electroquímicas , Electrodos , Infecciones por VIH/tratamiento farmacológico , Antígenos HLA-B/genética , Antígenos HLA-B/inmunología , HumanosRESUMEN
Elimination of malaria is a global health priority. Detecting an asymptomatic carrier of Plasmodium parasites to receive treatment is an important step in achieving this goal. Current available tools for detection of malaria parasites are either expensive, lacking in sensitivity for asymptomatic carriers, or low in throughput. We investigated the sensitivity of an impedimetric biosensor targeting the malaria biomarker Plasmodium lactate dehydrogenase (pLDH). Following optimization of the detection protocol, sensor performance was tested using phosphate-buffered saline (PBS), and then saliva samples spiked with pLDH at various concentrations. The presence of pLDH was determined by analyzing the sensor electrical properties before and after sample application. Through comparing percentage changes in impedance magnitude, the sensors distinguished pLDH-spiked PBS from non-spiked PBS at concentrations as low as 250 pg/mL (p = 0.0008). Percentage changes in impedance magnitude from saliva spiked with 2.5 ng/mL pLDH trended higher than those from non-spiked saliva. These results suggest that these biosensors have the potential to detect concentrations of pLDH up to two logs lower than currently available best-practice diagnostic tools. Successful optimization of this sensor platform would enable more efficient diagnosis of asymptomatic carriers, who can be targeted for treatment, contributing to the elimination of malaria.