Universal protocol for the wafer-scale manufacturing of 2D carbon-based transducer layers for versatile biosensor applications.

In this manuscript, we present a comprehensive fabrication protocol for high-performance graphene oxide (GO) sensor concepts. It is suitable for a variety of biosensing applications and contains the essential process steps, starting with vapor phase evaporation for siloxane monolayers, followed by spin-coating of GO as a nanometer-thin transducer with exceptional homogeneity and micromechanical surface methods which enable seamless transformation of GO transducers to be desired micro and nano dimensions. In addition to linking basic research and innovative sensor concepts with an outlook for commercial applications of point-of-care systems for early-stage diagnostics, the authors consider it necessary to take a closer look at the manufacturing processes to create more transparency and clarity, to manufacture such specific sensor concepts systematically. The detailed manufacturing approaches are intended to motivate practitioner to explore and improve this GO-based key technology. This process development is illustrated below using the manufacturing methods for three types of sensors, namely sensors based on i) surface plasmon resonance spectroscopy (SPR), ii) impedance spectroscopy and iii) bio-field effect transistors (ISFETs). The obtained results in this work prove successful GO sensor productions by achieving:•Uniform and stable immobilization of GO thin films,•High yield of sensor units on a wafer scale, here up to 96 %,•Promising integration potential for various biomedical sensor concepts to early-stage diagnostic.

Reduced graphene oxide biosensor platform for the detection of NT-proBNP biomarker in its clinical range.

Reduced graphene oxide (rGO) thin films can be exploited as highly sensitive transducer layers and integrated in interdigital micro-electrode systems for biosensing processes. The distinctive bipolar characterisitics of rGO thin films can be modulated by a very low external electric field due to the electrostatic charges of biomolecules. These charges lead to a fast response in the readout signals of rGO based ion sensitive field-effect transistors (ISFETs). The characterisitc changes of rGO ISFETs enable a fast, accurate and reproducible detection of biomolecules. The biosensing mechanism offers a fast and label-free approach for analyte detection in contrast to the classical ELISA method. In this contribution, we introduce a reproducible fabrication process of rGO based field-effect transistors on wafer level. The sensors are functionalized as biosensors to measure N-terminal pro-brain natriuretic peptide (NT-proBNP) in human serum within its clinical range. Our optimized rGO sensor shows very promising electrical properties and can be considered as a proof of concept study for the detection of various analytes. The easy and cost-effective fabrication as well as the versatile usability make this new technological platform an auspicious tool for different sensing applications in future.

Reduced graphene-oxide transducers for biosensing applications beyond the Debye-screening limit.

In the field of label-free biosensing, various transducer materials and strategies are under investigation to overcome the Debye-screening limitation of charged biomolecules. We demonstrate an in-line, impedimetric aptasensor with reduced graphene-oxide (rGO) thin films as transducers to detect prostate specific antigens (PSA) in a physiological buffer solution. Unlike classical electrochemical impedance spectroscopy (EIS), this direct, label-free and fully-electronic biosensor approach does not need any redox markers. As specific capture molecules, short anti-PSA aptamers ensured a close binding of the target molecules to the transducer surfaces. Results showed a limit of detection smaller than 33 pM of PSA and a wide detection range from 0.033 to 330 nM fully covering the clinically relevant range of PSA (0.115-0.290 nM). This promising performance can be attributed to the bipolar electronic transport characteristics of the ultra-thin rGO layers similar to pristine graphene. The attachment of target biomolecules to the films changes the resistance of the rGO thin films. Such an in-line EIS configuration with rGO thin films opens promising prospects for biosensing beyond the Debye-screening limitation, which is a major challenge for conventional semiconductor field-effect devices towards clinical applications.

Silane Deposition via Gas-Phase Evaporation and High-Resolution Surface Characterization of the Ultrathin Siloxane Coatings.

Siloxane coatings for surfaces are essential in many scientific and industrial applications. We describe a straightforward gas-phase evaporation technique in inert atmosphere and introduce a practical and reliable silanization protocol adaptable to different silane types. The primary aim of depositing ultrathin siloxane films on surfaces is to enable a reproducible and homogenous surface functionalization without agglomeration effects during the layer formation. To realize high-quality and large-area coatings, it is fundamental to understand the reaction conditions of the silanes, the process of the siloxane layer formation, and the possible influence of the substrate morphology. We used three typical silane types to exemplify the potential and versatility of our process: aminopropyltriethoxysilane, glycidoxypropyltrimethoxysilane, and 1 H,1 H,2 H,2 H-perfluorooctyl-trichlorosilane. The ultrathin siloxane layers, which are generally difficult to characterize, were precisely investigated with high-resolution surface-characterization methods to verify our concept in terms of reproducibility and coating quality. Our results show that this gas-phase evaporation protocol is easily adaptable to all three, widely used silane types also enabling a large-area upscale.