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Analog neuromorphic computing systems emulate the parallelism and connectivity of the human brain, promising greater expressivity and energy efficiency compared to those of digital systems. Though many devices have emerged as candidates for artificial neurons and artificial synapses, there have been few device candidates for artificial dendrites. In this work, we report on biocompatible graphene-based artificial dendrites (GrADs) that can implement dendritic processing. By using a dual side-gate configuration, current applied through a Nafion membrane can be used to control device conductance across a trilayer graphene channel, showing spatiotemporal responses of leaky recurrent, alpha, and Gaussian dendritic potentials. The devices can be variably connected to enable higher-order neuronal responses, and we show through data-driven spiking neural network simulations that spiking activity is reduced by ≤15% without accuracy loss while low-frequency operation is stabilized. This positions the GrADs as strong candidates for energy efficient bio-interfaced spiking neural networks.
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Two-dimensional (2D) transition metal dichalcogenide (TMD) layers are highly promising as field-effect transistor (FET) channels in the atomic-scale limit. However, accomplishing this superiority in scaled-up FETs remains challenging due to their van der Waals (vdW) bonding nature with respect to conventional metal electrodes. Herein, we report a scalable approach to fabricate centimeter-scale all-2D FET arrays of platinum diselenide (PtSe2) with in-plane platinum ditelluride (PtTe2) edge contacts, mitigating the aforementioned challenges. We realized a reversible transition between semiconducting PtSe2 and metallic PtTe2 via a low-temperature anion exchange reaction compatible with the back-end-of-line (BEOL) processes. All-2D PtSe2 FETs seamlessly edge-contacted with transited metallic PtTe2 exhibited significant performance improvements compared to those with surface-contacted gold electrodes, e.g., an increase of carrier mobility and on/off ratio by over an order of magnitude, achieving a maximum hole mobility of â¼50.30 cm2 V-1 s-1 at room temperature. This study opens up new opportunities toward atomically thin 2D-TMD-based circuitries with extraordinary functionalities.
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Due to the developing resistance and intolerance to antiretroviral drugs, there is an urgent demand for alternative agents that can suppress the viral load in people living with human immunodeficiency virus (HIV). Recently, there has been increased interest in agents of marine origin such as, in particular, fucoidans to suppress HIV replication. In the present study, the anti-HIV-1 activity of fucoidans from the brown algae Alaria marginata, Alaria ochotensis, Laminaria longipes, Saccharina cichorioides, Saccharina gurianovae, and Tauya basicrassa was studied in vitro. The studied compounds were found to be able to inhibit HIV-1 replication at different stages of the virus life cycle. Herewith, all fucoidans exhibited significant antiviral activity by affecting the early stages of the virus-cell interaction. The fucoidan from Saccharina cichorioides showed the highest virus-inhibitory activity by blocking the virus' attachment to and entry into the host's cell, with a selectivity index (SI) > 160.
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Fármacos Anti-VIH , VIH-1 , Phaeophyceae , Polisacáridos , Replicación Viral , Phaeophyceae/química , VIH-1/efectos de los fármacos , Fármacos Anti-VIH/farmacología , Polisacáridos/farmacología , Humanos , Replicación Viral/efectos de los fármacos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virologíaRESUMEN
Viruses cause various infections that may affect human lifestyle for durations ranging from several days to for many years. Although preventative and therapeutic remedies are available for many viruses, they may still have a profound impact on human life. The human immunodeficiency virus type 1 is the most common cause of HIV infection, which represents one of the most dangerous and complex diseases since it affects the immune system and causes its disruption, leading to secondary complications and negatively influencing health-related quality of life. While highly active antiretroviral therapy may decrease the viral load and the velocity of HIV infection progression, some individual peculiarities may affect viral load control or the progression of T-cell malfunction induced by HIV. Our study is aimed at the text-based identification of molecular mechanisms that may be involved in viral infection progression, using HIV as a case study. Specifically, we identified human proteins and genes which commonly occurred, overexpressed or underexpressed, in the collections of publications relevant to (i) HIV infection progression and (ii) acute and chronic stages of HIV infection. Then, we considered biological processes that are controlled by the identified protein and genes. We verified the impact of the identified molecules in the associated clinical study.
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Infecciones por VIH , VIH-1 , Humanos , Calidad de Vida , Terapia Antirretroviral Altamente Activa , Minería de Datos , Carga ViralRESUMEN
This review provides a critical overview of current developments on nanoelectronic biochemical sensors based on graphene. Composed of a single layer of conjugated carbon atoms, graphene has outstanding high carrier mobility and low intrinsic electrical noise, but a chemically inert surface. Surface functionalization is therefore crucial to unravel graphene sensitivity and selectivity for the detection of targeted analytes. To achieve optimal performance of graphene transistors for biochemical sensing, the tuning of the graphene surface properties via surface functionalization and passivation is highlighted, as well as the tuning of its electrical operation by utilizing multifrequency ambipolar configuration and a high frequency measurement scheme to overcome the Debye screening to achieve low noise and highly sensitive detection. Potential applications and prospectives of ultrasensitive graphene electronic biochemical sensors ranging from environmental monitoring and food safety, healthcare and medical diagnosis, to life science research, are presented as well.
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Técnicas Biosensibles , Electrónica , Grafito , CarbonoRESUMEN
Iron deficiency (ID) is the most prevalent and severe nutritional disorder globally and is the leading cause of iron deficiency anemia (IDA). IDA often progresses subtly symptomatic in children, whereas prolonged deficiency may permanently impair development. Early detection and frequent screening are, therefore, essential to avoid the consequences of IDA. In order to reduce the production cost and complexities involved in building advanced ID sensors, the devices were fabricated using a home-built patterning procedure that was developed and used for this work instead of lithography, which allows for fast prototyping of dimensions. In this article, we report the development of graphene-based field-effect transistors (GFETs) functionalized with anti-ferritin antibodies through a linker molecule (1-pyrenebutanoic acid, succinimidyl ester), to facilitate specific conjugation with ferritin antigen. The resulting biosensors feature an unprecedented ferritin detection limit of 10 fM, indicating a tremendous potential for non-invasive (e.g., saliva) ferritin detection.
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Anemia Ferropénica , Técnicas Biosensibles , Grafito , Anemia Ferropénica/diagnóstico , Niño , Diagnóstico Precoz , Ferritinas/análisis , HumanosRESUMEN
Human Immunodeficiency Virus Type 1 (HIV-1) infection is associated with high mortality if no therapy is provided. Currently, the treatment of an HIV-1 positive patient requires that several drugs should be taken simultaneously. The resistance of the virus to an antiretroviral drug may lead to treatment failure. Our approach focuses on predicting the exposure of a particular viral variant to an antiretroviral drug or drug combination. It also aims at the prediction of drug treatment success or failure. We utilized nucleotide sequences of HIV-1 encoding protease and reverse transcriptase to perform such types of prediction. The PASS (Prediction of Activity Spectra for Substances) algorithm based on the naive Bayesian classifier was used to make a prediction. We calculated the probability of whether a sequence belonged (P1) or did not belong (P0) to the class associated with exposure of the viral sequence to the set of drugs that can be associated with resistance to the set of drugs. The accuracy calculated as the average Area Under the ROC (Receiver Operating Characteristic) Curve (AUC/ROC) for classifying exposure of the sequence to the HIV-1 protease inhibitors was 0.81 (±0.07), and for HIV-1 reverse transcriptase, it was 0.83 (±0.07). To predict cases of treatment effectiveness or failure, we used P1 and P0 values, obtained in PASS, along with the binary vector constructed based on short nucleotide descriptors and the applied random forest classifier. Average AUC/ROC prediction accuracy for the prediction of treatment effectiveness or failure for the combinations of HIV-1 protease inhibitors was 0.82 (±0.06) and of HIV-1 reverse transcriptase was 0.76 (±0.09).
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Algoritmos , Fármacos Anti-VIH/farmacología , Área Bajo la Curva , Teorema de Bayes , Farmacorresistencia Viral , Quimioterapia Combinada , Proteasa del VIH/química , Proteasa del VIH/genética , Inhibidores de la Proteasa del VIH/farmacología , Transcriptasa Inversa del VIH/química , Transcriptasa Inversa del VIH/genética , VIH-1/genética , Humanos , Inhibidores de la Transcriptasa Inversa/farmacología , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
In this Letter, the ambipolar properties of an electrolyte-gated graphene field-effect transistor (GFET) have been explored to fabricate frequency-doubling biochemical sensor devices. By biasing the ambipolar GFETs in a common-source configuration, an input sinusoidal voltage at frequency f applied to the electrolyte gate can be rectified to a sinusoidal wave at frequency 2f at the drain electrode. The extraordinary high carrier mobility of graphene and the strong electrolyte gate coupling provide the graphene ambipolar frequency doubler an unprecedented unity gain, as well as a detection limit of â¼4 pM for 11-mer single strand DNA molecules in 1 mM PBS buffer solution. Combined with an improved drift characteristics and an enhanced low-frequency 1/f noise performance by sampling at doubled frequency, this good detection limit suggests the graphene ambipolar frequency doubler a highly promising biochemical sensing platform.
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Técnicas Biosensibles/métodos , ADN de Cadena Simple/análisis , Grafito/química , Técnicas Biosensibles/instrumentaciónRESUMEN
Objective.Making up one of the largest shares of diagnosed cancers worldwide, skin cancer is also one of the most treatable. However, this is contingent upon early diagnosis and correct skin cancer-type differentiation. Currently, methods for early detection that are accurate, rapid, and non-invasive are limited. However, literature demonstrating the impedance differences between benign and malignant skin cancers, as well as between different types of skin cancer, show that methods based on impedance differentiation may be promising.Approach.In this work, we propose a novel approach to rapid and non-invasive skin cancer diagnosis that leverages the technologies of difference-based electrical impedance tomography (EIT) and graphene electronic tattoos (GETs).Main results.We demonstrate the feasibility of this first-of-its-kind system using both computational numerical and experimental skin phantom models. We considered variations in skin cancer lesion impedance, size, shape, and position relative to the electrodes and evaluated the impact of using individual and multi-electrode GET (mGET) arrays. The results demonstrate that this approach has the potential to differentiate based on lesion impedance, size, and position, but additional techniques are needed to determine shape.Significance.In this way, the system proposed in this work, which combines both EIT and GET technology, exhibits potential as an entirely non-invasive and rapid approach to skin cancer diagnosis.
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Impedancia Eléctrica , Grafito , Fantasmas de Imagen , Neoplasias Cutáneas , Tomografía , Grafito/química , Tomografía/instrumentación , Tomografía/métodos , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/diagnóstico por imagen , Humanos , Electrodos , TatuajeRESUMEN
OBJECTIVE: The study aimed to compare the prevalence of surveillance HIV drug resistance mutations (SDRMs) across the main federal districts of Russia. METHODS: A pooled analysis was conducted to examine data on HIV primary drug resistance (HIV PrimDR). The analysis was based on published results primarily from Russian regional clinical and scientific laboratories, covering a span of 20 years. RESULTS: The findings indicate that three surveyed regions, namely Central, Far Eastern, and Volga, exhibit a low level of HIV PrimDR prevalence (not exceeding 5%), and this prevalence does not show a tendency to increase. In contrast, three major regions, namely Northwestern, Southern, and Siberian, demonstrate a significant and progressive increase in HIV PrimDR prevalence, with recent values surpassing 10%. CONCLUSION: Consequently, it was concluded that a change in the HIV treatment strategy in these regions is imperative, emphasizing the need to expedite the transition to the utilization of secondgeneration integrase inhibitors.
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Fármacos Anti-VIH , Infecciones por VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico , Mutación , Federación de Rusia/epidemiología , Prevalencia , Farmacorresistencia Viral/genética , GenotipoRESUMEN
Graphene, a 2D carbon allotrope, is revolutionizing many biomedical applications due to its unique mechanical, electrical, thermal, and optical properties. When bioengineers realized that these properties could dramatically enhance the performance of cardiac sensors and actuators and may offer fundamentally novel technological capabilities, the field exploded with numerous studies developing new graphene-based systems and testing their limits. Here we will review the link between specific properties of graphene and mechanisms of action of cardiac sensors and actuators, analyze the performance of these systems from inaugural studies to the present, and offer future perspectives.
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More than 50% of all people living with HIV worldwide are women. Globally, HIV/AIDS is the leading cause of death among women aged 15 to 44. The safe and effective methods of hormonal contraception are an essential component of preventive medical care in order to reduce maternal and infant mortality. However, there is limited knowledge regarding the effect of hormones on the rate of viral replication in HIV infection, especially non-B subtypes. The goal of the present work was to study in vitro how the female hormones ß-estradiol and progesterone affect the replication of the HIV-1 subtypes A6, CRF02_AG, and B. The findings show that high doses of hormones enhanced the replication of HIV-1 sub-subtype A6 by an average of 1.75 times and the recombinant variant CRF02_AG by 1.4 times but did not affect the replication of HIV-1 subtype B. No difference was detected in the expression of CCR5 and CXCR4 co-receptors on the cell surface, either in the presence or absence of hormones. However, one of the reasons for the increased viral replication could be the modulated TLRs secretion, as it was found that high doses of estradiol and progesterone upregulated, to varying degrees, the expression of TLR2 and TLR9 genes in the PBMCs of female donors infected with HIV-1 sub-subtype A6.
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The SARS-CoV-2 pandemic has highlighted the need for devices capable of carrying out rapid differential detection of viruses that may manifest similar physiological symptoms yet demand tailored treatment plans. Seasonal influenza may be exacerbated by COVID-19 infections, increasing the burden on healthcare systems. In this work, we demonstrate a technology based on liquid-gated graphene field-effect transistors (GFETs), for rapid and ultraprecise sensing and differentiation of influenza and SARS-CoV-2 surface protein. Most distinctively, the device consists of 4 onboard GFETs arranged in a quadruple architecture, where each quarter is functionalized individually (with either antibodies or chemically passivated control) but measured jointly. The sensor platform was tested against a range of concentrations of viral surface proteins from both viruses with the lowest tested and detected concentration at â¼50 ag/mL, or 88 zM for COVID-19 and 227 zM for Flu, which is 5-fold lower than the values reported previously on a similar platform. Unlike the classic real-time polymerase chain reaction test, which has a turnaround time of a few hours, the graphene technology presents an ultrafast response time of â¼10 s even in complex and clinically relevant media such as saliva. Thus, we have developed a multianalyte, highly sensitive, and fault-tolerant technology for rapid diagnostic of contemporary, emerging, and future pandemics.
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COVID-19 , Grafito , Gripe Humana , Humanos , SARS-CoV-2 , COVID-19/diagnóstico , AnticuerposRESUMEN
The organized self-assembly of conductive biological structures holds promise for creating new bioelectronic devices. In particular, Geobacter sulfurreducens type IVa pili have proven to be a versatile material for fabricating protein nanowire-based devices. To scale the production of conductive pili, we designed a strain of Shewanella oneidensis that heterologously expressed abundant, conductive Geobacter pili when grown aerobically in liquid culture. S. oneidensis expressing a cysteine-modified pilin, designed to enhance the capability to bind to gold, generated conductive pili that self-assembled into biohybrid filaments in the presence of gold nanoparticles. Elemental composition analysis confirmed the filament-metal interactions within the structures, which were several orders of magnitude larger than previously described metal:organic filaments. The results demonstrate that the S. oneidensis chassis significantly advances the possibilities for facile conductive protein nanowire design and fabrication.
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Técnicas Biosensibles , Geobacter , Nanopartículas del Metal , Oro , Fimbrias Bacterianas/metabolismo , Transporte de ElectrónRESUMEN
Heart rhythm disorders, known as arrhythmias, cause significant morbidity and are one of the leading causes of mortality. Cardiac arrhythmias are frequently treated by implantable devices, such as pacemakers and defibrillators, or by ablation therapy guided by electroanatomical mapping. Both implantable and ablation therapies require sophisticated biointerfaces for electrophysiological measurements of electrograms and delivery of therapeutic stimulation or ablation energy. In this work, a graphene biointerface for in vivo cardiac electrophysiology is reported for the first time. Leveraging sub-micrometer-thick tissue-conformable graphene arrays, sensing and stimulation of the open mammalian heart are demonstrated both in vitro and in vivo. Furthermore, the graphene biointerface treatment of atrioventricular block (the kind of arrhythmia where the electrical conduction from the atria to the ventricles is interrupted) is demonstrated. The graphene arrays show effective electrochemical properties, namely interface impedance down to 40 Ω cm2 at 1 kHz, charge storage capacity up to 63.7 mC cm-2 , and charge injection capacity up to 704 µC cm-2 . Transparency of the graphene structures allows for simultaneous optical mapping of cardiac action potentials, calcium transients, and optogenetic stimulation while performing electrical measurements and stimulation. The report presents evidence of the significant potential of graphene biointerfaces for advanced cardiac electrophysiology and arrhythmia therapy.
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Grafito , Animales , Humanos , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/terapia , Corazón , Ventrículos Cardíacos , MamíferosRESUMEN
In Russia, antiretroviral therapy (ART) coverage has significantly increased, which, in the absence of routine genotyping testing, could lead to an increase in HIV drug resistance (DR). The aim of this study was to investigate the patterns and temporal trends in HIV DR as well as the prevalence of genetic variants in treatment-naïve patients from 2006 to 2022, using data from the Russian database (4481 protease and reverse transcriptase and 844 integrase gene sequences). HIV genetic variants, and DR and DR mutations (DRMs) were determined using the Stanford Database. The analysis showed high viral diversity, with the predominance of A6 (78.4%), which was the most common in all transmission risk groups. The overall prevalence of surveillance DRMs (SDRMs) was 5.4%, and it reached 10.0% in 2022. Most patients harbored NNRTI SDRMs (3.3%). The prevalence of SDRMs was highest in the Ural (7.9%). Male gender and the CRF63_02A6 variant were association factors with SDRMs. The overall prevalence of DR was 12.7% and increased over time, primarily due to NNRTIs. Because baseline HIV genotyping is unavailable in Russia, it is necessary to conduct surveillance of HIV DR due to the increased ART coverage and DR prevalence. Centralized collection and unified analysis of all received genotypes in the national database can help in understanding the patterns and trends in DR to improve treatment protocols and increase the effectiveness of ART. Moreover, using the national database can help identify regions or transmission risk groups with a high prevalence of HIV DR for epidemiological measures to prevent the spread of HIV DR in the country.
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Fármacos Anti-VIH , Infecciones por VIH , Seropositividad para VIH , VIH-1 , Humanos , Masculino , VIH-1/genética , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico , Farmacorresistencia Viral/genética , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Mutación , Genotipo , Prevalencia , Federación de Rusia/epidemiologíaRESUMEN
Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited. To ease and to expedite their deployment, here, we identify bottlenecks hindering the maturation of flexible sensors and propose promising solutions. We first analyze challenges in achieving satisfactory sensing performance for real-world applications and then summarize issues in compatible sensor-biology interfaces, followed by brief discussions on powering and connecting sensor networks. Issues en route to commercialization and for sustainable growth of the sector are also analyzed, highlighting environmental concerns and emphasizing nontechnical issues such as business, regulatory, and ethical considerations. Additionally, we look at future intelligent flexible sensors. In proposing a comprehensive roadmap, we hope to steer research efforts towards common goals and to guide coordinated development strategies from disparate communities. Through such collaborative efforts, scientific breakthroughs can be made sooner and capitalized for the betterment of humanity.
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Dispositivos Electrónicos Vestibles , Humanos , Calidad de VidaRESUMEN
A major challenge for graphene applications is the lack of mass production technology for large-scale and high-quality graphene growth and transfer. Here, a roll-to-roll (R2R) dry transfer process for large-scale graphene grown by chemical vapor deposition is reported. The process is fast, controllable, and environmentally benign. It avoids chemical contamination and allows the reuse of graphene growth substrates. By controlling tension and speed of the R2R dry transfer process, the electrical sheet resistance is achieved as 9.5 kΩ sq-1 , the lowest ever reported among R2R dry transferred graphene samples. The R2R dry transferred samples are used to fabricate graphene-based field-effect transistors (GFETs) on polymer. It is demonstrated that these flexible GFETs feature a near-zero doping level and a gate leakage current one to two orders of magnitude lower than those fabricated using wet-chemical etched graphene samples. The scalability and uniformity of the R2R dry transferred graphene is further demonstrated by successfully transferring a 3 × 3 in2 sample and measuring its field-effect mobility with 36 millimeter-scaled GFETs evenly spaced on the sample. The field-effect mobility of the R2R dry transferred graphene is determined to be 205 ± 36 cm2 V-1 .
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Continuous monitoring of arterial blood pressure (BP) in non-clinical (ambulatory) settings is essential for understanding numerous health conditions, including cardiovascular diseases. Besides their importance in medical diagnosis, ambulatory BP monitoring platforms can advance disease correlation with individual behaviour, daily habits and lifestyle, potentially enabling analysis of root causes, prognosis and disease prevention. Although conventional ambulatory BP devices exist, they are uncomfortable, bulky and intrusive. Here we introduce a wearable continuous BP monitoring platform that is based on electrical bioimpedance and leverages atomically thin, self-adhesive, lightweight and unobtrusive graphene electronic tattoos as human bioelectronic interfaces. The graphene electronic tattoos are used to monitor arterial BP for >300 min, a period tenfold longer than reported in previous studies. The BP is recorded continuously and non-invasively, with an accuracy of 0.2 ± 4.5 mm Hg for diastolic pressures and 0.2 ± 5.8 mm Hg for systolic pressures, a performance equivalent to Grade A classification.