RESUMEN
Cortisol, a steroid hormone mostly known as "the stress hormone," plays many essential functions in humans due its involvement in several metabolic pathways. It is well-known that cortisol dysregulation is implied in evolution and progression of several chronic pathologies, including cardiac diseases such as heart failure (HF). However, although several sensors have been proposed to date for the determination of cortisol, none of them has been designed for its determination in saliva in order to monitor HF progression. In this work, a silicon nitride based Immuno field-effect transistor (ImmunoFET) has been proposed to quantify salivary cortisol for HF monitoring. Sensitive biological element was represented by anti-cortisol antibody bound onto the ISFET gate via 11-triethoxysilyl undecanal (TESUD) by vapor-phase method. Potentiometric and electrochemical impedance spectroscopy (EIS) measurements were carried out for preliminary investigations on device responsiveness. Subsequently, a more sensitive detection was obtained using electrochemical EIS. The proposed device has proven to have a linear response (R2 always >0.99), to be sensitive (with a limit of detection, LoD, of 0.005 ± 0.002 ng/mL), selective in case of other HF biomarkers (e.g. N-terminal pro B-type natriuretic peptide (NT-proBNP), tumor necrosis factor-alpha (TNF-α), and interleukin 10 (IL-10)), and accurate in cortisol quantification in saliva sample by performing the standard addition method.
Asunto(s)
Insuficiencia Cardíaca , Hidrocortisona , Humanos , Espectroscopía Dieléctrica , Insuficiencia Cardíaca/diagnóstico , Biomarcadores , Saliva , Fragmentos de PéptidosRESUMEN
According to the European statistics, approximately 26 million patients worldwide suffer from heart failure (HF), and this number seems to be steadily increasing. Inflammation plays a central role in the development of HF, and the pro-inflammatory cytokine Tumor necrosis factor-α (TNF-α) represents inflammation gold-standard biomarker. Early detection plays a crucial role for the prognosis and treatment of HF. An Ion Sensitive Field Effect Transistor (ISFET) based on silicon nitride transducer and biofunctionalized with anti-TNF-α antibody for label-free detection of salivary TNF-α is proposed. Electrochemical impedance spectroscopy (EIS) was used for TNF-α detection. Our ImmunoFET offered a detection limit of 1 pg mL-1, with an analytical reproducibility expressed by a coefficient of variance (CV) resulted < 10% for the analysis of saliva samples, and an analyte recovery of 94 ± 6%. In addition, it demonstrated high selectivity when compared to other HF biomarkers such as Inteleukin-10, N-terminal pro B-type natriuretic peptide, and Cortisol. Finally, ImmunoFET accuracy in determining the unknown concentration of TNF-α was successfully tested in saliva samples by performing standard addition method. The proposed ImmunoFET showed great promise as a complementary tool for biomedical application for HF monitoring by a non-invasive, rapid and accurate assessment of TNF-α.
Asunto(s)
Técnicas Biosensibles , Insuficiencia Cardíaca , Insuficiencia Cardíaca/diagnóstico , Humanos , Inmunoensayo , Reproducibilidad de los Resultados , Saliva , Compuestos de Silicona , Factor de Necrosis Tumoral alfaRESUMEN
Biosensors based on field-effect devices (bioFETs) offer numerous advantages over current technologies and therefore have attracted immense research over the decades. However, short Debye screening length in highly ionic physiological solutions remains the main obstacle for bioFET realization. This challenge becomes considerably more acute at the electrolyte-oxide interface of the sensing area due to high ion concentration induced by the charged amphoteric sites, which prohibits any attempt to employ the field-effect mechanism to "sense" any charged biomolecules. In this work, we present an electrostatic approach by which the double layer (DL) excess ion concentration is removed, thus forcing the DL ion concentration to match the bulk concentration, which subsequently forces bulk screening length at the DL, thereby "exposing" target biomolecules to the underlying bioFET. To this end, we employ local tunable surface electric fields, introduced to the DL using surface passivated-metal electrodes. We examine numerically and analytically the effect of these electric fields on the DL ion distribution. We also numerically demonstrate the feasibility of the proposed approach for a fully depleted silicon-on-insulator based bioFET and show how the threshold voltage shift induced by the presence of target molecules increases by almost two orders of magnitude upon the removal of the surface excess ion population.
Asunto(s)
Técnicas Biosensibles/instrumentación , Electrodos/normas , Electricidad EstáticaRESUMEN
The importance of specific and label-free detection of proteins via antigen-antibody interactions for the development of point-of-care testing devices has greatly influenced the search for a more accessible, sensitive, low cost and robust sensors. The vision of silicon field-effect transistor (FET)-based sensors has been an attractive venue for addressing the challenge as it potentially offers a natural path to incorporate sensors with the existing mature Complementary Metal Oxide Semiconductor (CMOS) industry; this provides a stable and reliable technology, low cost for potential disposable devices, the potential for extreme minituarization, low electronic noise levels, etc. In the current review we focus on silicon-based immunological FET (ImmunoFET) for specific and label-free sensing of proteins through antigen-antibody interactions that can potentially be incorporated into the CMOS industry; hence, immunoFETs based on nano devices (nanowire, nanobelts, carbon nanotube, etc.) are not treated here. The first part of the review provides an overview of immunoFET principles of operation and challenges involved with the realization of such devices (i.e. e.g. Debye length, surface functionalization, noise, etc.). In the second part we provide an overview of the state-of-the-art silicon-based immunoFET structures and novelty, principles of operation and sensing performance reported to date.