Beyond the Debye length in high ionic strength solution: direct protein detection with field-effect transistors (FETs) in human serum

Detecting proteins at low concentrations in high-ionic-strength conditions by silicon nanowire field-effect transistors (SiNWFETs) is severely hindered due to the weakened signal, primarily caused by screening effects. In this study, aptamer as a signal amplifier, which has already been reported by our group, is integrated into SiNWFET immunosensors employing antigen-binding fragments (Fab) as the receptors to improve its detection limit for the first time. The Fab-SiNWFET immunosensors were developed by immobilizing Fab onto Si surfaces modified with either 3-aminopropyltriethoxysilane (APTES) and glutaraldehyde (GA) (Fab/APTES-SiNWFETs), or mixed self-assembled monolayers (mSAMs) of polyethylene glycol (PEG) and GA (Fab/PEG-SiNWFETs), to detect the rabbit IgG at different concentrations in a high-ionic-strength environment (150 mM Bis-Tris Propane) followed by incubation with R18, an aptamer which can specifically target rabbit IgG, for signal enhancement. Empirical results revealed that the signal produced by the sensors with Fab probes was greatly enhanced compared to the ones with whole antibody (Wab) after detecting similar concentrations of rabbit IgG. The Fab/PEG-SiNWFET immunosensors exhibited an especially improved limit of detection to determine the IgG level down to 1 pg/mL, which has not been achieved by the Wab/PEG-SiNWFET immunosensors.

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Influence of the Electrolyte Salt Concentration on DNA Detection with Graphene Transistors

Biosensors ◽

10.3390/bios11010024 ◽

2021 ◽

Vol 11 (1) ◽

pp. 24

Author(s):

Agnes Purwidyantri ◽

Telma Domingues ◽

Jérôme Borme ◽

Joana Rafaela Guerreiro ◽

Andrey Ipatov ◽

...

Keyword(s):

Phosphate Buffer ◽

Species Interactions ◽

Field Effect ◽

Field Effect Transistors ◽

Limit Of Detection ◽

Debye Length ◽

Intermolecular Forces ◽

Single Layer Graphene ◽

Dna Adsorption

Liquid-gated Graphene Field-Effect Transistors (GFET) are ultrasensitive bio-detection platforms carrying out the graphene’s exceptional intrinsic functionalities. Buffer and dilution factor are prevalent strategies towards the optimum performance of the GFETs. However, beyond the Debye length (λD), the role of the graphene-electrolytes’ ionic species interactions on the DNA behavior at the nanoscale interface is complicated. We studied the characteristics of the GFETs under different ionic strength, pH, and electrolyte type, e.g., phosphate buffer (PB), and phosphate buffer saline (PBS), in an automatic portable built-in system. The electrostatic gating and charge transfer phenomena were inferred from the field-effect measurements of the Dirac point position in single-layer graphene (SLG) transistors transfer curves. Results denote that λD is not the main factor governing the effective nanoscale screening environment. We observed that the longer λD was not the determining characteristic for sensitivity increment and limit of detection (LoD) as demonstrated by different types and ionic strengths of measuring buffers. In the DNA hybridization study, our findings show the role of the additional salts present in PBS, as compared to PB, in increasing graphene electron mobility, electrostatic shielding, intermolecular forces and DNA adsorption kinetics leading to an improved sensitivity.

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The role of polarization-induced reorientation of DNA strands on organic field-effect transistor-based biosensors sensitivity at high ionic strength

Applied Physics Letters ◽

10.1063/1.4930303 ◽

2015 ◽

Vol 107 (10) ◽

pp. 103301 ◽

Cited By ~ 13

Author(s):

S. Lai ◽

M. Barbaro ◽

A. Bonfiglio

Keyword(s):

Ionic Strength ◽

Field Effect ◽

Field Effect Transistor ◽

High Ionic Strength ◽

Organic Field Effect Transistor ◽

Dna Strands ◽

Effect Transistor

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Aptamer–field-effect transistors overcome Debye length limitations for small-molecule sensing

Science ◽

10.1126/science.aao6750 ◽

2018 ◽

Vol 362 (6412) ◽

pp. 319-324 ◽

Cited By ~ 142

Author(s):

Nako Nakatsuka ◽

Kyung-Ae Yang ◽

John M. Abendroth ◽

Kevin M. Cheung ◽

Xiaobin Xu ◽

...

Keyword(s):

Conformational Changes ◽

Field Effect ◽

Field Effect Transistors ◽

Debye Length ◽

Stem Loop ◽

Highly Sensitive ◽

Close Proximity ◽

Sphingosine 1 Phosphate ◽

Specific Receptors ◽

Highly Sensitive Detection

Detection of analytes by means of field-effect transistors bearing ligand-specific receptors is fundamentally limited by the shielding created by the electrical double layer (the “Debye length” limitation). We detected small molecules under physiological high–ionic strength conditions by modifying printed ultrathin metal-oxide field-effect transistor arrays with deoxyribonucleotide aptamers selected to bind their targets adaptively. Target-induced conformational changes of negatively charged aptamer phosphodiester backbones in close proximity to semiconductor channels gated conductance in physiological buffers, resulting in highly sensitive detection. Sensing of charged and electroneutral targets (serotonin, dopamine, glucose, and sphingosine-1-phosphate) was enabled by specifically isolated aptameric stem-loop receptors.

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Specific detection of biomolecules in physiological solutions using graphene transistor biosensors

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1625010114 ◽

2016 ◽

Vol 113 (51) ◽

pp. 14633-14638 ◽

Cited By ~ 95

Author(s):

Ning Gao ◽

Teng Gao ◽

Xiao Yang ◽

Xiaochuan Dai ◽

Wei Zhou ◽

...

Keyword(s):

Ionic Strength ◽

Real Time ◽

Protein Detection ◽

High Ionic Strength ◽

Polymer Layer ◽

General Strategy ◽

Detection Of Biomolecules ◽

Permeable Polymer ◽

Graphene Devices ◽

Modified Graphene

Nanomaterial-based field-effect transistor (FET) sensors are capable of label-free real-time chemical and biological detection with high sensitivity and spatial resolution, although direct measurements in high–ionic-strength physiological solutions remain challenging due to the Debye screening effect. Recently, we demonstrated a general strategy to overcome this challenge by incorporating a biomolecule-permeable polymer layer on the surface of silicon nanowire FET sensors. The permeable polymer layer can increase the effective screening length immediately adjacent to the device surface and thereby enable real-time detection of biomolecules in high–ionic-strength solutions. Here, we describe studies demonstrating both the generality of this concept and application to specific protein detection using graphene FET sensors. Concentration-dependent measurements made with polyethylene glycol (PEG)-modified graphene devices exhibited real-time reversible detection of prostate specific antigen (PSA) from 1 to 1,000 nM in 100 mM phosphate buffer. In addition, comodification of graphene devices with PEG and DNA aptamers yielded specific irreversible binding and detection of PSA in pH 7.4 1x PBS solutions, whereas control experiments with proteins that do not bind to the aptamer showed smaller reversible signals. In addition, the active aptamer receptor of the modified graphene devices could be regenerated to yield multiuse selective PSA sensing under physiological conditions. The current work presents an important concept toward the application of nanomaterial-based FET sensors for biochemical sensing in physiological environments and thus could lead to powerful tools for basic research and healthcare.

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Enhancement of protein detection performance in field-effect transistors with polymer residue-free graphene channel

Carbon ◽

10.1016/j.carbon.2013.05.069 ◽

2013 ◽

Vol 62 ◽

pp. 312-321 ◽

Cited By ~ 12

Author(s):

Jin Heak Jung ◽

Il Yung Sohn ◽

Duck Jin Kim ◽

Bo Yeong Kim ◽

Mi Jang ◽

...

Keyword(s):

Field Effect ◽

Field Effect Transistors ◽

Protein Detection ◽

Detection Performance ◽

Free Graphene

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Targeting Antibodies to Carbon Nanotube Field Effect Transistors by Pyrene Hydrazide Modification of Heavy Chain Carbohydrates

Journal of Nanotechnology ◽

10.1155/2012/490175 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 5

Author(s):

Steingrimur Stefansson ◽

Hena H. Kwon ◽

Saeyoung Nate Ahn

Keyword(s):

Carbon Nanotube ◽

Field Effect ◽

Field Effect Transistors ◽

Polyclonal Antibodies ◽

Debye Length ◽

E Coli ◽

Immobilized Antibodies ◽

Large Size ◽

Antibody Orientation ◽

Effect Transistor

Many carbon nanotube field-effect transistor (CNT-FET) studies have used immobilized antibodies as the ligand binding moiety. However, antibodies are not optimal for CNT-FET detection due to their large size and charge. Their size can prevent ligands from reaching within the Debye length of the CNTs and a layer of charged antibodies on the circuits can drown out any ligand signal. In an attempt to minimize the antibody footprint on CNT-FETs, we examined whether pyrene hydrazide modification of antibody carbohydrates could reduce the concentration required to functionalize CNT circuits. The carbohydrates are almost exclusively on the antibody Fc region and this site-specific modification could mediate uniform antibody orientation on the CNTs. We compared the hydrazide modification of anti-E. coliO157:H7 polyclonal antibodies to pyrenebutanoic acid succinimidyl ester-coated CNTs and carbodiimide-mediated antibody CNT attachment. Our results show that the pyrene hydrazide modification was superior to those methods with respect to bacteria detection and less than 1 nM labeled antibody was required to functionalize the circuits.

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