Magnetite-Based Biosensors and Molecular Logic Gates: From Magnetite Synthesis to Application

Abstract

In the last few decades, point-of-care (POC) sensors have become increasingly important in the detection of various targets for the early diagnostics and treatment of diseases. Diverse nanomaterials are used as building blocks for the development of smart biosensors and magnetite nanoparticles (MNPs) are among them. The intrinsic properties of MNPs, such as their large surface area, chemical stability, ease of functionalization, high saturation magnetization, and more, mean they have great potential for use in biosensors. Moreover, the unique characteristics of MNPs, such as their response to external magnetic fields, allow them to be easily manipulated (concentrated and redispersed) in fluidic media. As they are functionalized with biomolecules, MNPs bear high sensitivity and selectivity towards the detection of target biomolecules, which means they are advantageous in biosensor development and lead to a more sensitive, rapid, and accurate identification and quantification of target analytes. Due to the abovementioned properties of functionalized MNPs and their unique magnetic characteristics, they could be employed in the creation of new POC devices, molecular logic gates, and new biomolecular-based biocomputing interfaces, which would build on new ideas and principles. The current review outlines the synthesis, surface coverage, and functionalization of MNPs, as well as recent advancements in magnetite-based biosensors for POC diagnostics and some perspectives in molecular logic, and it also contains some of our own results regarding the topic, which include synthetic MNPs, their application for sample preparation, and the design of fluorescent-based molecular logic gates.

Keywords: biosensors; magnetite nanoparticles (MNPs); molecular logic; point-of-care testing; surface functionalization.

Figure 1

The main routes of MNP synthesis.

Figure 2

A TEM image of MNPs synthesized via the co-precipitation method (the results obtained in the laboratory of the presenting authors).

Figure 3

A TEM-image of MNPs synthesized via the partial oxidation of ferrous hydroxide (the results obtained in the laboratory of the presenting authors).

Figure 4

Schematic representation of the two main types of magnetite nanoparticle functionalization processes for medical applications: in situ and postsynthesis functionalization (reproduced without modification with permission from [69]).

Figure 5

TEM-image of MNPs with silica coverage (the results obtained in the laboratory of the presenting authors).

Figure 6

Frontiers constructing the bionano interface, which is constituted by the nanoparticle surface, the biomolecule, and the medium (reproduced without modification with permission from [44]).

Figure 7

Comparison of the usage of commercial adsorbent (line 1) and synthesized silica-magnetite nanocomposite (line 2) for isolation of virus DNA fragments from sugar beet using agarose gel electrophoresis. Line M–DNA markers [100].

Figure 8

An overview of the functionality and methodology of MP-based biosensors for point-of-care testing (reprinted with permission from [111]).

Figure 9

Schematic representation of the detection method based on optical and electrochemical techniques (Colorimetry, Surface-enhanced Raman spectroscopy (SERS), Surface Plasmon Resonance (SPR), Fluorescence, Potentiometry, Conductivity, Amperometry, and Electronic Impedance Spectroscopy (EIS)) combined with magnetic materials for biosensing (reprinted with modification with permission from [12]).

Figure 10

NMR biosensor based on nuclear magnetic resonance for detection of Salmonella: (A) representation for preparation of Fe₃O₄ nanoparticles (NP) and Fe₃O₄-streptavidin nanoparticles (NPC-SA); (B) overview of NMR biosensor for detection of Salmonella in milk (reprinted with permission from [124]).

Figure 11

Composition of SARS-CoV-2 virus, the scheme for detection of anti-SARS-CoV-2 immunoglobulin M (IgM) and G (IgG)using the test strip, the magnetic immune system device, and medical applications (reprinted with permission from [134]).

Figure 12

Overview of proposed POC, SARS-CoV-2 N, or S protein-specific biotinylated aptamer-based COVID-19 assay. In the first step, saliva is added to this cocktail. In the second step, the viral antigen or the SARS-CoV-2 virion binding is released. In the third step, the magnetic separation of magnetic nanoparticles conjugated to the aptamer-antigen complex is used. In the final step, the remaining solution is collected and incubated with sucrose. Invertase, which is contained in the solution, converts sucrose to glucose which can be directly measured using a portable glucometer. The glucose concentration is correlated with the SARS-CoV-2 N or S protein concentration (reprinted with permission from [136]).

Figure 13

Schematic of SERS aptasensor based on graphene oxide (GO)-wrapped Fe₃O₄@Au nanostructures for V. parahaemolyticus determination (reprinted with permission from [141]).

Figure 14

General description of an INH gate and the subsequent truth table (0 means low signal, 1 means high signal) (reprinted with permission from [149]).

Figure 15

Proposed mechanism of fluorescent chromophore NTPA for assay of Cu²⁺ and PPi (reprinted with permission from [150]).

Figure 16

Illustration of artifacts and typical contrast agents that give high MRI contrast effects in either T₁ or T₂ but do not satisfy AND logic (a,b) and artifact filtering imaging agent (AFIA) that fulfills AND logic (c) (reprinted from [153] with permission of ©2014 American Chemical Society).

Figure 17

Schematic representation of the assembly of nanoparticles to construct logical AND (left) or logical OR (right) by attachment of protease removable polyethylene glycol polymers (reprinted from [154] with permission of ©2007 American Chemical Society).

Figure 18

A standard architecture for a computer design (a) and a proposed biomolecular computing structure (b) (reprinted with permission from [155]).