Label-free field-effect transistor-based immunosensors are promising candidates for proteomics and peptidomics-based diagnostics and therapeutics due to their high multiplexing capability, fast response time, and ability to increase the sensor sensitivity due to the short length of peptides. In this work, planar junctionless field-effect transistor sensors (FETs) were fabricated and characterized for pH sensing. The device with SiO₂ gate oxide has shown voltage sensitivity of 41.8 ± 1.4, 39.9 ± 1.4, 39.0 ± 1.1, and 37.6 ± 1.0 mV/pH for constant drain currents of 5, 10, 20, and 50 nA, respectively, with a drain to source voltage of 0.05 V. The drift analysis shows a stability over time of −18 nA/h (pH 7.75), −3.5 nA/h (pH 6.84), −0.5 nA/h (pH 4.91), 0.5 nA/h (pH 3.43), corresponding to a pH drift of −0.45, −0.09, −0.01, and 0.01 per h. Theoretical modeling and simulation resulted in a mean value of the surface states of 3.8 × 10¹⁵/cm² with a standard deviation of 3.6 × 10¹⁵/cm². We have experimentally verified the number of surface sites due to APTES, peptide, and protein immobilization, which is in line with the theoretical calculations for FETs to be used for detecting peptide-protein interactions for future applications.

In this paper we report an acid-modulated strategy for novel peptide microarray production on biosensor interfaces. We initially selected a controlled pore glass (CPG) as a support for solid-phase peptide synthesis (SPPS) to implement a chemistry that can be performed at the interface of multiple field effect transistor (FET) sensors, eventually to generate label-free peptide microarrays for protein screening. Our chemistry uses a temporary protection of the N-terminal amino function of each amino acid building block with a tert-butyloxycarbonyl (Boc) group that can be removed after each SPPS cycle, in combination with semi-permanent protection of the side chains of trifunctional amino acid residues. Such a protection scheme with a well-proven record of application in conventional, batchwise SPPS has been fine-tuned for optimal performance on CPG and, from there, translated to SPR chips that allow layer-by-layer monitoring of amino acid coupling. Our results validate this acid-modulated synthesis as a feasible approach for producing peptides in high yields and purity on flat glass surfaces, such as those in bio-FETs.

Sensors to monitor the immune status of an individual play a crucial role in understanding the acquired immunity or signs of a latent infection. Such sensors can be an effective tool to manage infection and to design treatment options in vulnerable populations. We demonstrate here highly sensitive detection of acquired immunity to Cytomegalovirus CMV by detection of anti-CMV antibodies using plasmon-enhanced fluorescence (PEF). The PEF sensors leverage plasmonic enhancement from a high density of intense electromagnetic hotspots in self-assembly-derived gold nanopillar arrays. Comparing PEF assays with assays on a planar surface plasmon resonance sensor shows the PEF sensors to be sensitive to a small fraction of the antibodies on the surface. The detection scheme deploys peptide monolayers with specific affinity to anti-CMV antibodies to capture them onto the sensor surfaces. The results of the assay on the PEF sensor reveal high promise for sensors with miniaturized sensing footprints, ease of spatial multiplexing, high sensitivity, and quick response times. The developments are readily applicable to a range of other diagnostic contexts where peptide–protein interactions and self-assembly-derived PEF sensors can be leveraged.

The drive to miniaturize sensing footprints to the micro- and nanoscale has been motivated by reduced sensor real estate, lower sample consumption, and quick response times. However, there remains a limited understanding of how reducing sensor active areas impacts analyte–sensor interactions at fixed analyte concentrations. Using gold nanoparticles as a model analyte, we demonstrate that diminishing sensor active areas are associated with a nonlinear enhancement of analyte surface densities without changing the solution concentration. This behavior is rationalized by correlating the reduced sensor dimensions to an increase in the “effective” analyte availability per surface site. Consequently, sensors with reduced footprints would require substantially fewer analyte molecules to achieve surface densities comparable to those of macroscopic sensors. The resulting increase in nanoparticle surface density further translates into enhanced signal intensities in surface-enhanced Raman detection, arising from the higher density of nanoparticle–substrate plasmonic hotspots within a fixed optical measurement footprint. Overall, the work highlights how micro- and nanoscale sensors with active areas approaching the dimensions of the measurement footprint of highly sensitive transducers (e.g., nanowires or plasmonic hotspots) maximize the benefits of sensor miniaturization.

In this paper we report a novel acid-modulated strategy for peptide microarray production on biosensor interfaces. We have initially selected controlled pore glass (CPG) as support for solid phase peptide synthesis (SPPS) to implement a chemistry that can be efficiently performed at the interface of multiple FET sensors, eventually to generate label-free peptide microarrays for protein screening. Our chemistry uses temporary protection of the N-terminal amino function of each amino acid building block with a tert-butyloxycarbonyl (Boc) group that can be removed after each SPPS cycle, in combination with semi-permanent protection of the side chains of trifunctional amino acid residues. Such protection scheme, with a well-proven record of application in conventional, batchwise SPPS, has been fine tuned for optimal performance on CPG and, from there, translated to SPR chips that allow layer-by-layer monitoring of amino acid coupling. Our results validate this acid-modulated synthesis as a feasible approach for producing peptides in high yield and purity on flat glass surfaces such as those in bio-FETs.

In the ElectroMed project, we are interested in screening certain peptide sequences for their ability to selectively interact with antibodies or MHC proteins. This poses a combinatorial challenge that requires a highly multiplexed setup of label-free immunosensors. Label-free FET-based immunosensors are good candidates due to their high multiplexing capability and fast response time. Nanowire-based FET sensors have shown high sensitivity but are unreliable for clinical applications due to drift and gate stability issues. To address this, a label-free immuno-FET architecture based on planar junctionless FET devices is proposed. This geometry can improve the signal-to-noise ratio due to its larger planar structure, which is less prone to defects that cause noise and is better suited to the functionalization of different receptor molecules.