Label-Free C-Reactive Protein Si Nanowire FET Sensor Arrays With Super-Nernstian Back-Gate Operation

We present a CMOS-compatible double gate and label-free C-reactive protein (CRP) sensor, based on silicon on insulator (SOI) silicon nanowires arrays. We exploit a reference subtracted detection method and a super-Nernstian internal amplification given by the double gate structure. We overcome the Debye screening of charged CRP proteins in solutions using antibodies fragments as capturing probes, reducing the overall thickness of the capture layer. We demonstrate the internal amplification through the pH response of the sensor, in static and real-time working modes. While operated in back-gate configuration, the sensor shows excellent stability (<20 pA/min in the worst case), low hysteresis (<300 mV), and a great sensitivity up to 1.2 nA/dec toward CRP proteins in the linear response range. The reported system is an excellent candidate for the continuous monitoring of inflammation biomarkers in serum or interstitial fluid

Biosensing of Cardiac Biomarkers Using Single Polyaniline Nanowires

In this thesis, we explore innovative methods of fabricating single polymer nanowires and applying the fabricated single polymer nanowires for biosensors. The fabrication of single polymer nanowire was carried out via electrochemical deposition growth method, which deposits ionized molecules in a pre-patterned nanochannel between two Au electrodes and forms a nanowire. For biosensing application, we employ polyaniline (PANI) in this research since it has advantages of biocompatibility, easy synthesis, and broad range of electrical conductivity. The single PANI nanowires-based biosensor show high sensitivity and good sensing reliability due to the high surface to volume ratio and single nanowires. Using the fabricated single PANI nanowires, the biosensors were developed to detect cardiac biomarkers such as myoglobin (Myo), cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), and B-type natriuretic peptide (BNP). The single PANI nanowires are functionalized by surface immobilization method that was developed in our laboratory using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-Hydroxysuccinimde (NHS) to attach monoclonal antibodies (mAbs) of biomarkers without pre-chemical or physical treatments. Lastly, microfluidic devices including channels and solution infusion/withdrawal system were integrated on the biosensor in order to develop an all-in-one biosensor. Our single PANI nanowire-based biosensor is unique in terms of the functionalization on specific area; the mAbs are immobilized on the only surface of PANI nanowires because PANI has superior biocompatibility to mAbs unlike SiO2 layer or Au electrodes. This advantage reduces functionalization steps comparing to inorganic nanowire biosensors and frees the interfered signals from non-nanowire areas. In addition, the microfluidic channel helps achieving stable electrical signals, high sensitivity, safe sample handling, and minimal damage of nanowire. The integrated single PANI nanowire biosensors with microfluidic devices detect very low concentrations of Myo (100 pg/mL), cTnI (250 fg/mL), CK-MB (150 fg/mL), and BNP (50 fg/mL) with good specificity. The remarkable specificity value in cardiac biomarker sensing is over 106 fold, that the specificity value is defined as the ratio of [the highest concentration of non-specific protein showing ignorable or non-response signal] to [the lowest concentration of specific protein showing significant signal change], in the test of bovine serum albumin (BSA) or other cardiac markers. The single PANI nanowire biosensors have shown linear sensing profiles along different concentration from hundreds fg/mL to tens ng/mL depending on the mAbs of the specific biomarkers, and exhibit fast response in a few minutes satisfying reference values of Myo, cTnI, CK-MB, and BNP to diagnose heart failure and determine the patient’s stage of disease

Nanomaterials for Healthcare Biosensing Applications

In recent years, an increasing number of nanomaterials have been explored for their applications in biomedical diagnostics, making their applications in healthcare biosensing a rapidly evolving field. Nanomaterials introduce versatility to the sensing platforms and may even allow mobility between different detection mechanisms. The prospect of a combination of different nanomaterials allows an exploitation of their synergistic additive and novel properties for sensor development. This paper covers more than 290 research works since 2015, elaborating the diverse roles played by various nanomaterials in the biosensing field. Hence, we provide a comprehensive review of the healthcare sensing applications of nanomaterials, covering carbon allotrope-based, inorganic, and organic nanomaterials. These sensing systems are able to detect a wide variety of clinically relevant molecules, like nucleic acids, viruses, bacteria, cancer antigens, pharmaceuticals and narcotic drugs, toxins, contaminants, as well as entire cells in various sensing media, ranging from buffers to more complex environments such as urine, blood or sputum. Thus, the latest advancements reviewed in this paper hold tremendous potential for the application of nanomaterials in the early screening of diseases and point-of-care testing

Nanochips and medical applications

Ο όρος «νανοτσιπ» αναφέρεται σε ένα ολοκληρωμένο κύκλωμα (τσιπ) με νανοϋλικά και δομές στη νανοκλίμακα (1-100nm). Ένα ολοκληρωμένο κύκλωμα είναι μια συλλογή ηλεκτρονικών εξαρτημάτων, όπως τρανζίστορ, δίοδοι, πυκνωτές και αντιστάσεις. Τα σημερινά τρανζίστορ είναι στη νανοκλίμακα, αλλά μπορούν να τροποποιηθούν με νανοδομές για την κατασκευή βιοαισθητήρων που μπορούν να πραγματοποιούν ανίχνευση βιομορίων, όπως ιόντα, μόρια DNA, αντισώματα και αντιγόνα με μεγάλη ευαισθησία. Υλικά και Μέθοδοι: Πραγματοποιήθηκε συστηματική αναζήτηση βιβλιογραφίας με χρήση των ηλεκτρονικών βάσεων δεδομένων PubMed, Google Scholar και Scopus για την ανάπτυξη και χρήση νανοτσίπ σε ιατρικές εφαρμογές. Για τον προσδιορισμό των σχετικών εργασιών, τα κριτήρια συμπερίληψης αναφέρονται σε άρθρα στην αγγλική γλώσσα, άρθρα βιβλιογραφικού περιεχομένου ή/και έρευνών. Τα κριτήρια αποκλεισμού ήταν άρθρα εφημερίδων, περιλήψεις συνεδρίων και επιστολές. Αποτελέσματα: Τεχνικές in-vivo και in-vitro έχουν χρησιμοποιηθεί για την ανίχνευση μορίων DNA, ιόντων, αντισωμάτων, σημαντικών πρωτεϊνών και καρκινικών δεικτών, όχι μόνο από δείγματα αίματος αλλά και από ιδρώτα, σάλιο και άλλα βιολογικά υγρά. Διαγνωστική εφαρμογή των νανοτσίπ αποτελεί και η ανίχνευση πτητικών οργανικών ενώσεων μέσω τεστ εκπνεόμενης αναπνοής. Υπάρχουν και αρκετές θεραπευτικές εφαρμογές αυτών των συσκευών ημιαγωγών όπως τσιπ διασύνδεσης εγκεφάλου-υπολογιστή για παραλυτικές ή επιληπτικές καταστάσεις, κατασκευή «βιονικών» οργάνων όπως τεχνητός αμφιβληστροειδής, τεχνητό δέρμα και ρομποτικά προθετικά άκρα για ακρωτηριασμένους ή ρομποτική χειρουργική. Συμπέρασμα: Η χρήση των νανοτσίπ στην ιατρική είναι ένας αναδυόμενος τομέας με αρκετές θεραπευτικές εφαρμογές όπως η διάγνωση, η παρακολούθηση της υγείας και της φυσικής κατάστασης και η κατασκευή «βιονικών» οργάνων.Background: The term “nanochip” pertains to an integrated circuit (chip) with nanomaterials and components in the nano-dimension (1-100nm). An integrated circuit is essentially a collection of electronic components, like transistors, diodes, capacitors, and resistors. Current transistors are in the nanoscale but can also be modified with nanostructures like nanoribbons and nanowires to manufacture biosensors that can perform label-free, ultrasensitive detection of biomolecules like ions, DNA molecules, antibodies and antigens. Materials and Methods: A systematic literature search was conducted using the electronic databases PubMed, Google Scholar and Scopus for the development and use of nanochips in medical applications. For the identification of relevant papers, the inclusion criteria referred to articles in the English language, review and/or research articles. The exclusion criteria were newspaper articles, conference abstracts and letters. Results: In-vivo and In-vitro techniques have been used for detection of DNA molecules, ions, antibodies, important proteins, and tumor markers, not only from blood samples but also from sweat, saliva and other biological fluids. Another diagnostic application of nanochips is detection of volatile organic compounds via a breath test. There are also several therapeutic applications of these semiconductor devices like brain-computer interface chips for paralytic or epileptic conditions, manufacture of “bionic” organs like artificial retinas, artificial skin and robotic prostheses for amputees or robotic surgery. Conclusion: The use of nanochips in medicine is an emerging field with several therapeutic applications like diagnostics, health and fitness monitoring, and manufacture of “bionic” organs

Detection of Cardiac Biomarkers Using Single Polyaniline Nanowire-Based Conductometric Biosensors

The detection of myoglobin (Myo), cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), and b-type natriuretic peptide (BNP) plays a vital role in diagnosing cardiovascular diseases. Here we present single site-specific polyaniline (PANI) nanowire biosensors that can detect cardiac biomarkers such as Myo, cTnI, CK-MB, and BNP with ultra-high sensitivity and good specificity. Using single PANI nanowire-based biosensors integrated with microfluidic channels, very low concentrations of Myo (100 pg/mL), cTnI (250 fg/mL), CK-MB (150 fg/mL), and BNP (50 fg/mL) were detected. The single PANI nanowire-based biosensors displayed linear sensing profiles for concentrations ranging from hundreds (fg/mL) to tens (ng/mL). In addition, devices showed a fast (few minutes) response satisfying respective reference conditions for Myo, cTnI, CK-MB, and BNP diagnosis of heart failure and for determining the stage of the disease. This single PANI nanowire-based biosensor demonstrated superior biosensing reliability with the feasibility of label free detection and improved processing cost efficiency due to good biocompatibility of PANI to monoclonal antibodies (mAbs). Therefore, this development of single PANI nanowire-based biosensors can be applied to other biosensors for cancer or other diseases

Sensors and Biosensors for C-Reactive Protein, Temperature and pH, and Their Applications for Monitoring Wound Healing: A Review

Wound assessment is usually performed in hospitals or specialized labs. However, since patients spend most of their time at home, a remote real time wound monitoring would help providing a better care and improving the healing rate. This review describes the advances in sensors and biosensors for monitoring the concentration of C-reactive protein (CRP), temperature and pH in wounds. These three parameters can be used as qualitative biomarkers to assess the wound status and the effectiveness of therapy. CRP biosensors can be classified in: (a) field effect transistors, (b) optical immunosensors based on surface plasmon resonance, total internal reflection, fluorescence and chemiluminescence, (c) electrochemical sensors based on potentiometry, amperometry, and electrochemical impedance, and (d) piezoresistive sensors, such as quartz crystal microbalances and microcantilevers. The last section reports the most recent developments for wearable non-invasive temperature and pH sensors suitable for wound monitoring

Electrical and Electro-Optical Biosensors

Electrical and electro-optical biosensing technologies are critical to the development of innovative POCT devices, which can be used by both professional and untrained personnel for the provision of necessary health information within a short time for medical decisions to be determined, being especially important in an era of global pandemics. This Special Issue includes a few pioneering works concerning biosensors utilizing electrochemical impedance, localized surface plasmon resonance, and the bioelectricity of sensing materials in which the amount of analyte is pertinent to the signal response. The presented results demonstrate the potential of these label-free biosensing approaches in the detection of disease-related small-molecule metabolites, proteins, and whole-cell entities

Frequency dependence of dielectrophoretic fabrication of single-walled carbon nanotube field-effect transistors

A new theoretical model for the dielectrophoretic (DEP) fabrication of single-walled carbon nanotubes (SWCNTs) is presented. A different frequency interval for the alignment of wide-energy-gap semiconductor SWCNTs is obtained, exhibiting a considerable difference from the prevalent model. Two specific models are study, namely the spherical model and the ellipsoid model, to estimate the frequency interval. Then, the DEP process is performed and the obtained frequencies (from the spherical and ellipsoid models) are used to align the SWCNTs. These empirical results confirm the theoretical predictions, representing a crucial step towards the realization of carbon nanotube field-effect transistors (CNT-FETs) via the DEP process based on the ellipsoid model. © 2020, The Author(s)