Reviews

2023

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Aptamer-functionalized capacitive biosensors

S. Weaver; M. Mohammadi; N. Nakatsuka 

The growing use of aptamers as target recognition elements in label-free biosensing necessitates corresponding transducers that can be used in relevant environments. While popular in many fields, capacitive sensors have seen relatively little, but growing use in conjunction with aptamers for sensing diverse targets. Few reports have shown physiologically relevant sensitivity in laboratory conditions and a cohesive picture on how target capture modifies the measured capacitance has been lacking. In this review, we assess the current state of the field in three areas: small molecule, protein, and cell sensing. We critically analyze the proposed hypotheses on how aptamer-target capture modifies the capacitance, as many mechanistic postulations appear to conflict between published works. As the field matures, we encourage future works to investigate individual aptamer-target interactions and to interrogate the physical mechanisms leading to measured changes in capacitance. To this point, we provide recommendations on best practices for developing aptasensors with a particular focus on considerations for biosensing in clinical settings.

Biosensors and Bioelectronics

2023-03-15

Vol. 224 , p. 115014.

DOI : 10.1016/j.bios.2022.115014

2022

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Aptamer-modified biosensors to visualize neurotransmitter flux

C. Moraldo; E. Vuille-Dit-Bille; B. Shkodra; T. Kloter; N. Nakatsuka 

Chemical biosensors with the capacity to continuously monitor various neurotransmitter dynamics can be powerful tools to understand complex signaling pathways in the brain. However, in vivo detection of neurochemicals is challenging for many reasons such as the rapid release and clearance of neurotransmitters in the extracellular space, or the low target analyte concentrations in a sea of interfering biomolecules. Biosensing platforms with adequate spatiotemporal resolution coupled to specific and selective receptors termed aptamers, demonstrate high potential to tackle such challenges. Herein, we review existing literature in this field. We first discuss nanoparticle-based systems, which have a simple in vitro implementation and easily interpretable results. We then examine methods employing near-infrared detection for deeper tissue imaging, hence easier translation to in vivo implementation. We conclude by reviewing live cell imaging of neurotransmitter release via aptamer-modified platforms. For each of these sensors, we discuss the associated challenges for translation to real-time in vivo neurochemical imaging. Realization of in vivo biosensors for neurotransmitters will drive future development of early prevention strategies, treatments, and therapeutics for psychiatric and neurodegenerative diseases.

Journal of Neuroscience Methods

2022-01-01

Vol. 365 , p. 109386.

DOI : 10.1016/j.jneumeth.2021.109386

2021

Electrolyte-gated carbon nanotube field-effect transistorbased biosensors: Principles and applications

B. Shkodra; M. Petrelli; M. Angeli; D. Garoli; N. Nakatsuka et al. 

Nowadays, there is a high demand for sensitive and selective real-time analytical methods suitable for a wide range of applications, from personalized telemedicine, drug discovery, food safety, and quality control, to defense, security, as well as environmental monitoring. Biosensors are analytical devices able to detect bio-chemical analytes (e.g., neurotransmitters, cancer biomarkers, bio-molecules, and ions), through the combination of a bio-recognition element and a bio-transduction device. The use of customized bio-recognition elements such as enzymes, antibodies, aptamers, and ion-selective membranes facilitates achieving high selectivity. Among the different bio-transduction devices currently available, electrolyte-gated field-effect transistors, in which the dielectric is represented by an ionic liquid buffer solution containing the targeted analyte, are gaining increasing attention. Indeed, these biotransduction devices are characterized by superior electronic properties and intrinsic signal amplification that allow the detection of a wide range of biomolecules with high sensitivity (down to pM concentration). A promising semiconducting material for bio-transduction devices is represented by carbon nanotubes, due to their unique electrical properties, nanosize, bio-compatibility, and their simple low-cost processability. This work provides a comprehensive and critical review of electrolyte-gated carbon nanotube field-effect transistor-based biosensors. First, an introduction to these bio-sensing devices is given. Next, the device configurations and operating principles are presented, and the most used materials and processes are reviewed with a particular focus on carbon nanotubes as the active material. Subsequently, different functionalization strategies reported in the literature, based on enzymes, antibodies, aptamers, and ion-selective membranes, are analyzed critically. Finally, present issues and challenges faced in the area are investigated, the conclusions are drawn, and a perspective outlook over the field of bio-sensing technologies, in general, is provided.

Applied Physics Reviews

2021-12-21

Vol. 8 , p. 041325.

DOI : 10.1063/5.0058591

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Nonspecific Binding—Fundamental Concepts and Consequences for Biosensing Applications

A. Frutiger; A. Tanno; S. Hwu; R. Tiefenauer; J. Vörös et al. 

Nature achieves differentiation of specific and nonspecific binding in molecular interactions through precise control of biomolecules in space and time. Artificial systems such as biosensors that rely on distinguishing specific molecular binding events in a sea of nonspecific interactions have struggled to overcome this issue. Despite the numerous technological advancements in biosensor technologies, nonspecific binding has remained a critical bottleneck due to the lack of a fundamental understanding of the phenomenon. To date, the identity, cause, and influence of nonspecific binding remain topics of debate within the scientific community. In this review, we discuss the evolution of the concept of nonspecific binding over the past five decades based upon the thermodynamic, intermolecular, and structural perspectives to provide classification frameworks for biomolecular interactions. Further, we introduce various theoretical models that predict the expected behavior of biosensors in physiologically relevant environments to calculate the theoretical detection limit and to optimize sensor performance. We conclude by discussing existing practical approaches to tackle the nonspecific binding challenge in vitro for biosensing platforms and how we can both address and harness nonspecific interactions for in vivo systems.

Chemical Reviews

2021-06-09

Vol. 121 , num. 13, p. 8095–8160.

DOI : 10.1021/acs.chemrev.1c00044