Graphene Sensor Arrays for Rapid and Accurate Detection of Pancreatic Cancer Exosomes in Patients' Blood Plasma Samples.

Biosensors based on graphene field effect transistors (GFETs) have the potential to enable the development of point-of-care diagnostic tools for early stage disease detection. However, issues with reproducibility and manufacturing yields of graphene sensors, but also with Debye screening and unwanted detection of nonspecific species, have prevented the wider clinical use of graphene technology. Here, we demonstrate that our wafer-scalable GFETs array platform enables meaningful clinical results. As a case study of high clinical relevance, we demonstrate an accurate and robust portable GFET array biosensor platform for the detection of pancreatic ductal adenocarcinoma (PDAC) in patients' plasma through specific exosomes (GPC-1 expression) within 45 min. In order to facilitate reproducible detection in blood plasma, we optimized the analytical performance of GFET biosensors via the application of an internal control channel and the development of an optimized test protocol. Based on samples from 18 PDAC patients and 8 healthy controls, the GFET biosensor arrays could accurately discriminate between the two groups while being able to detect early cancer stages including stages 1 and 2. Furthermore, we confirmed the higher expression of GPC-1 and found that the concentration in PDAC plasma was on average more than 1 order of magnitude higher than in healthy samples. We found that these characteristics of GPC-1 cancerous exosomes are responsible for an increase in the number of target exosomes on the surface of graphene, leading to an improved signal response of the GFET biosensors. This GFET biosensor platform holds great promise for the development of an accurate tool for the rapid diagnosis of pancreatic cancer.

Ultrasensitive detection of SARS-CoV-2 spike protein by graphene field-effect transistors.

COVID-19, caused by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), originated a global health crisis, causing over 2 million casualties and altering human daily life all over the world. This pandemic emergency revealed the limitations of current diagnostic tests, highlighting the urgency to develop faster, more precise and sensitive sensors. Graphene field effect transistors (GFET) are analytical platforms that enclose all these requirements. However, the design of a sensitive and robust GFET is not a straightforward objective. In this work, we report a GFET array biosensor for the detection of SARS-CoV-2 spike protein using the human membrane protein involved in the virus internalisation: angiotensin-converting enzyme 2 (ACE2). By finely controlling the graphene functionalisation, by tuning the Debye length, and by deeply characterising the ACE2-spike protein interactions, we have been able to detect the target protein with an extremely low limit of detection (2.94 aM). This work set the basis for a new class of analytical platforms, based on human membrane proteins, with the potential to detect a broad variety of pathogens, even before their isolation, being a powerful tool in the fight against future pandemics.

Utilidad de la detección del virus del papiloma humano en el cribado de neoplasia intraepitelial anal en pacientes con conductas de riesgo / Usefulness of human papillomavirus testing in anal intraepithelial neoplasia screening in a risk behaviour population

INTRODUCCIÓN: La incidencia de la neoplasia intraepitelial anal está en aumento en determinados grupos con conductas de riesgo, y en su etiopatogenia está implicada la infección por el virus del papiloma humano (VPH). Dentro de los programas de cribado implementados en las últimas décadas se encuentra el uso sistemático de la citología anal y, más recientemente, la detección del VPH mediante captura de híbridos y genotipado. MATERIAL Y MÉTODO: Estudio de cohortes retrospectivo de la población con conductas de riesgo de desarrollar neoplasia intraepitelial anal atendida en la consulta de Infecciones de Transmisión Sexual del área de Dermatología del Hospital Costa del Sol desde enero de 2010 a diciembre de 2012, a la que se le realizó cribado de neoplasia intraepitelial anal mediante toma de citología anal y genotipado de VPH. RESULTADOS: El 50% de la población estudiada tenía infección por VIH. Se encontró una alta frecuencia de displasia anal y presencia de VPH en la citología (82,1%) y genotipado (79%). Se obtuvo una asociación estadísticamente significativa (p < 0,005) entre la presencia de genotipos de VPH de alto riesgo y la presencia de displasia de alto grado en la segunda citología dirigida. El genotipado de VPH permitió identificar 17 casos (22%) de displasia severa infradiagnosticados en la primera citología. CONCLUSIÓN: La citología anal a ciegas puede infradiagnosticar casos de displasia de alto grado. La detección de VPH puede complementar este procedimiento, permitiéndonos identificar aquellos pacientes con mayor riesgo de desarrollar displasia anal de alto grado

INTRODUCTION: The incidence of intraepithelial anal neoplasia is increasing in certain risk behaviour groups, and human papillomavirus (HPV) infection is involved in its pathogenesis. The systematic use of anal cytology, and more recently HPV detection by hybrid capture and genotyping, have been introduced into screening programs in recent decades. MATERIAL AND METHODS: A retrospective cohort study was carried out on individuals with risk behaviours of developing intraepithelial anal neoplasia and who attended Sexually Transmitted Infections clinics in the Dermatology area of the Hospital Costa del Sol from January 2010 to December 2012. The intraepithelial anal neoplasia screening was performed using anal cytology and HPV genotyping. RESULTS: Half (50%) of the study population were HIV positive. A high frequency of anal dysplasia and presence of HPV in cytology (82.1%) and genotype (79%) was found. A statistically significant association (P < .005) was obtained between the presence of high-risk HPV genotypes and the presence of high-grade dysplasia in the second directed cytology. HPV genotyping enabled 17 cases (22%) of severe dysplasia to be identified that were under-diagnosed in the first cytology. CONCLUSION: Cases of high-grade dysplasia can be under-diagnosed by a first anal cytology. Detection of HPV can supplement this procedure, leading to the identification of those patients most at risk of developing high-grade anal dysplasia

[Usefulness of human papillomavirus testing in anal intraepithelial neoplasia screening in a risk behaviour population]. / Utilidad de la detección del virus del papiloma humano en el cribado de neoplasia intraepitelial anal en pacientes con conductas de riesgo.

INTRODUCTION: The incidence of intraepithelial anal neoplasia is increasing in certain risk behaviour groups, and human papillomavirus (HPV) infection is involved in its pathogenesis. The systematic use of anal cytology, and more recently HPV detection by hybrid capture and genotyping, have been introduced into screening programs in recent decades. MATERIAL AND METHODS: A retrospective cohort study was carried out on individuals with risk behaviours of developing intraepithelial anal neoplasia and who attended Sexually Transmitted Infections clinics in the Dermatology area of the Hospital Costa del Sol from January 2010 to December 2012. The intraepithelial anal neoplasia screening was performed using anal cytology and HPV genotyping. RESULTS: Half (50%) of the study population were HIV positive. A high frequency of anal dysplasia and presence of HPV in cytology (82.1%) and genotype (79%) was found. A statistically significant association (P<.005) was obtained between the presence of high-risk HPV genotypes and the presence of high-grade dysplasia in the second directed cytology. HPV genotyping enabled 17 cases (22%) of severe dysplasia to be identified that were under-diagnosed in the first cytology. CONCLUSION: Cases of high-grade dysplasia can be under-diagnosed by a first anal cytology. Detection of HPV can supplement this procedure, leading to the identification of those patients most at risk of developing high-grade anal dysplasia.

Screening of anal intraepithelial neoplasia in risk groups: Descriptive study of sexual habits and other sexual transmitted infections

Introducción: La neoplasia intraepitelial anal se considera una lesión precursora del carcinoma escamoso anal. La población de mayor riesgo de padecer esta lesión son pacientes inmunodeprimidos, especialmente los infectados por el virus de la inmunodeficiencia humana (VIH), con prácticas de sexo anal. El objetivo de este estudio fue describir los hábitos sexuales de los pacientes atendidos en la consulta de infecciones de transmisión sexual (ITS) en nuestro servicio, a los que se les realizó una citología anal, así como la presencia de otras ITS. Material y métodos: Se realizó un estudio descriptivo de aquellos pacientes a los que, de acuerdo con nuestro protocolo, se les realizó una citología anal entre 2008 y 2011. Asimismo, se realizó una encuesta sobre hábitos sexuales y cribado de otras ITS. Finalmente, se llevó a cabo un estudio descriptivo y analítico bivariado valorando la distribución de la alteración citológica y el grado de displasia anal. Resultados: Se incluyeron un total de 347 citologías anales, con un 48,1% de citologías alteradas. Se encontraron diferencias estadísticamente significativas entre la presencia de condilomas perianales/endoanales, la infección por VIH, la infección por Chlamydia trachomatis y la presencia de alteración citológica. Conclusión: La displasia anal tiene una alta prevalencia en nuestro medio en determinados grupos con hábitos sexuales de riesgo, pero probablemente esté infradiagnosticada por su carácter subclínico y la falta de un protocolo de cribado bien establecido (AU)

Background: Anal intraepithelial neoplasia is considered a precursor lesion of anal squamous carcinoma. The population with increased risk of this conditions are immunocompromised individuals, especially HIV-infected, with anal sex practices. The aim of this study was to describe the sexual habits of patients who were seen in sexually transmitted infections (STIs) consult in our service in whom anal cytology was performed as well as the association of anal dysplasia to other STIs. Material and methods: We performed a retrospective cohort study that included those patients in whom, according to our protocol, anal cytology was performed between 2008 and 2011. Also we conducted a survey on sexual habits and screening for other STIs. Finally, we conducted a descriptive and analytical study assessing bivariate distribution of cytological alterations and grade of anal dysplasia. Results: A total of 347 anal cytologies were performed, and 48.1% were abnormal. Statistically significant differences were found between the presence of condylomata perianal/endoanal, HIV infection, Chlamydia trachomatis infection and the presence of cytologic alterations. Conclusion: There was a high incidence of anal dysplasia in our group of individuals with risky sexual habits; however, it is probably underdiagnosed due to its subclinical nature and lack of a well-established screening protocol (AU)

[Screening of anal intraepithelial neoplasia in risk groups: descriptive study of sexual habits and other sexual transmitted infections]. / Cribado de neoplasia intraepitelial anal en grupos de riesgo: estudio descriptivo sobre hábitos sexuales y otras infecciones de transmisión sexual.

BACKGROUND: Anal intraepithelial neoplasia is considered a precursor lesion of anal squamous carcinoma. The population with increased risk of this conditions are immunocompromised individuals, especially HIV-infected, with anal sex practices. The aim of this study was to describe the sexual habits of patients who were seen in sexually transmitted infections (STIs) consult in our service in whom anal cytology was performed as well as the association of anal dysplasia to other STIs. MATERIAL AND METHODS: We performed a retrospective cohort study that included those patients in whom, according to our protocol, anal cytology was performed between 2008 and 2011. Also we conducted a survey on sexual habits and screening for other STIs. Finally, we conducted a descriptive and analytical study assessing bivariate distribution of cytological alterations and grade of anal dysplasia. RESULTS: A total of 347 anal cytologies were performed, and 48.1% were abnormal. Statistically significant differences were found between the presence of condylomata perianal/endoanal, HIV infection, Chlamydia trachomatis infection and the presence of cytologic alterations. CONCLUSION: There was a high incidence of anal dysplasia in our group of individuals with risky sexual habits; however, it is probably underdiagnosed due to its subclinical nature and lack of a well-established screening protocol.