¹ Laboratory of Nanobiotechnology, Institute of Biomedical Chemistry, Moscow, Russia

² Foundation of Perspective Technologies and Novations, Moscow, Russia

³ JSC Novosibirsk Plant of Semiconductor Devices with OKB, Novosibirsk, Russia

The concentration detection limit (DL) of biomacromolecules attainable using a nanowire detector has become a topical issue. A DL of 10⁻¹⁵ M is required to reveal oncological and infectious diseases at an early stage. This study discusses the DL experimentally attainable in the subfemtomolar concentration range, and possible mechanisms explaining such a low-concentration DL through the cooperative effect of biomacromolecular complexes formed on the surface of the nanowire (NW) chip near the nanowire.

Keywords: nanowire biosensor; ultrasensitive protein detection; detection limit; field-effect nanotransistor

Nanowire detectors are usually considered to be nanoelectronic devices containing a matrix of field-effect transistors, in which nanowires (nanoribbons, nanowires) are used as a gate; these devices allow one to detect biomacromolecules [1,2,3,4,5,6,7,8].

Detection of viral particles with nanowire biosensors has been reported [1]; the number of such studies is, however, low, since the detection of single viral particles is difficult due to the following circumstances. After immersion in a suspension of viral particles, a layer of proteins (which are present in unbound form even in highly purified preparations [9]) virtually immediately forms on the functionalized surface of nanostructures—as was demonstrated with the example of a 200 nm AFM probe [10]. This is why nanowire biosensors are, as a rule, used for the detection of proteins and nucleic acids at low (femtomolar and subfemtomolar, i.e., ≤10⁻¹⁵ M) concentrations [5,6,8,11,12].

The sensitive element in such devices is a nanowire, which represents an n- or p-channel of a field-effect nanotransistor, with the surface facing the analyte solution, and acts as a virtual gate. The operating principle of such devices is as follows. When a charged macromolecule (e.g., a protein or nucleic acid) adsorbs onto the surface of the nanowire, a change in the conductivity between the drain and the source of the field-effect transistor is observed. This change in conductivity is recorded in real time using an electronic system. Protein markers, microRNAs, circular RNAs and other macromolecules associated with socially significant diseases are used as target macromolecules for diagnostic purposes. To provide biospecific detection, the surface of the chip from the nanowire detector is functionalized with molecular probes, which specifically recognize the target macromolecules.

In nanowire biosensors, the nanowires normally have dimensions on a nanometer scale, being commensurable with the size of macromolecules. The nanometer-scale size allows one to increase the sensitivity by increasing the surface area-to-volume ratio [13]. For instance, a nanowire detector has a size of 10 nm to 10 μm (diameter for a nanowire; thickness for a nanoribbon). Usually, nanowire detectors are fabricated in the form of an array of field-effect transistors. One chip can accommodate up to 10 or more such transistors. The concentration detection limit experimentally attained with such detectors normally reaches 10⁻¹⁷ M to 10⁻¹⁵ M [5,11,12,14].

Such a low concentration detection limit is necessary for the detection of oncological and infectious diseases at an early stage [15]. However, the theoretical basis for the experimental achievement of such detection limits using currently existing models, based on macromolecular registration directly on the nanowire’s surface, is still being developed. This study discusses a possible mechanism of experimentally attaining femtomolar and subfemtomolar concentration detection limits using a nanowire detector.

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Ivanov, Y.D.; Tatur, V.Y.; Glukhov, A.V.; Ziborov, V.S. Concentration Sensitivity of Nucleic Acid and Protein Molecule Detection Using Nanowire Biosensors. Biophysica 2021, 1, 328-333. https://doi.org/10.3390/biophysica1030024