Biocompatible micromotors for biosensing

Abstract

Micro/nanomotors are nanoscale devices that have been explored in various fields, such as drug delivery, environmental remediation, or biosensing and diagnosis. The use of micro/nanomotors has grown considerably over the past few years, partially because of the advantages that they offer in the development of new conceptual avenues in biosensing. This is due to their propulsion and intermixing in solution compared with their respective static forms, which enables motion-based detection methods and/or decreases bioassay time. This review focuses on the impacts of micro/nanomotors on biosensing research in the last 2 years. An overview of designs for bioreceptor attachment to micro/nanomotors is given. Recent developments have focused on chemically propelled micromotors using external fuels, commonly hydrogen peroxide. However, the associated fuel toxicity and inconvenience of use in relevant biological samples such as blood have prompted researchers to explore new micro/nanomotor biosensing approaches based on biocompatible propulsion sources such as magnetic or ultrasound fields. The main advances in biocompatible propulsion sources for micro/nanomotors as novel biosensing platforms are discussed and grouped by their propulsion-driven forces. The relevant analytical applications are discussed and representatively illustrated. Moreover, envisioning future biosensing applications, the principal advantages of micro/nanomotor synthesis using biocompatible and biodegradable materials are given. The review concludes with a realistic drawing on the present and future perspectives.

Keywords: Biofluid; Biomedical analysis; Biosensing; Micromotors; Propulsion.

Fig. 1

MNM functionalization strategies for biosensing applications. (A) Tubular MNMs functionalized with antibodies for electrochemical detection of CRP sepsis biomarker detection. Reprinted with permission from [28]. (B) Janus MNMs modified with aptamers for motion-based sensing of DNA. Reprinted with permission from [34]. (C) Janus MNMs modified with peptides for the affinity fluorescence sensing of cholera toxin B. Reprinted with permission from [40]

Fig. 2

Enzymatic and biohybrid MNMs in biosensing applications. (A) Schematic illustration of enzymatic propulsion and uric acid detection by SiO2/NaYF4:Yb/Tm Janus nanomotors (a) and luminescence emission spectra of micromotors after the addition of different concentrations of uric acid (b). Reprinted with permission from [46]. (B) Design of the enantiosensitive boat and propulsion mechanism (a) clockwise and counterclockwise trajectory, as a function of the DOPA enantiomer present in solution (b) and curvature direct readout of enantiomeric excess (c). Reprinted with permission from [47]. (C) Design and mechanism of two-component system-based signal transduction in bacteria connects specific inputs with a measurable output response for a hybrid biosensor platform design (a) and B. subtilis hybrid biosensor microswimmer time-lapse images with fluorescence response in the presence of target bacitracin and inorganic cargo towing (b). Reprinted with permission from [50]

Fig. 3

Magnetic MNMs in biosensing applications. (A) Schematic illustration of the preparation of fluorescence and magnetic spore micromotors and the detection strategy for C. diff bacterial toxin from diluted hospital samples. Reprinted with permission from [53]. (B) SERS magnetic nanomotor probes for in vivo biosensing. (a) Schematic illustration of the fabrication and SERS sensing of the magnetic nanomotors. (b) Video snapshots of a magnetic nanomotor rotating inside a living cell at different time intervals. (c) Typical SERS spectra from the site of the magnetic nanomotor within an intracellular environment after rotation. Reprinted with modifications with permission from [56]. (C) Schematic representation of (i) MagRobots modified with antibody against SARS-CoV-2 spike protein (SP) that is (iii) driven using a transverse rotating magnetic field in the presence of SARS-CoV-2 SP and (ii) secondary antibody against SARS-CoV-2 SP labeled with Ag–AuNRs. (iv) MagRobots show collective self-assembly through the immunosandwich assay of SARS-CoV-2. (v) The detection was performed through hydrogen evolution reaction (HER) of Ag–AuNRs. Reprinted with permission from [58]

Fig. 4

Light-driven MNMs in biosensing applications. (A) Fabrication and self-propulsion of the matchlike nanomotor (a). Illustration (b) and video snapshots showing the phototactic behavior of the nanomotors (c). Light-guided biochemical SERS sensing by the phototactic nanomotor. Schematic illustrations of SERS sensing of crystal violet (d) and cancer cells (f). Raman spectra and intensity change of characteristic peaks of crystal violet (e) and cancer cells (g) before and after nanomotor light irradiation for 10 s. Reprinted with permission from [63]. (B) Schematic illustration of NIR-driven fluorescent magnetic nanomotor application for the isolation and detection of CTCs in blood samples. Reprinted with permission from [64]

Fig. 5

Ultrasound-driven MNMs in biosensing applications. (A) Schematic diagram of the ultrasound Au nanorod modification, biorecognition, and SERS sensing (a). SERS spectra of target DNA detection at different concentrations (b, c). Selectivity of the SERS signal between different target probes (d). Reprinted with permission from [68] (B) Schematic illustration of AIB1 detection in living cancer cells using ultrasound-propelled FAM-AIB1-apt-GO/AuNW motors based on OFF-ON fluorescence switching. Reprinted with permission from [69]