Frontiers of Medical Micro/Nanorobotics: in vivo Applications and Commercialization Perspectives Toward Clinical Uses

Abstract

The field of medical micro/nanorobotics holds considerable promise for advancing medical diagnosis and treatment due to their unique ability to move and perform complex task at small scales. Nevertheless, the grand challenge of the field remains in its successful translation towards widespread patient use. We critically address the frontiers of the current methodologies for in vivo applications and discuss the current and foreseeable perspectives of their commercialization. Although no "killer application" that would catalyze rapid commercialization has yet emerged, recent engineering breakthroughs have led to the successful in vivo operation of medical micro/nanorobots. We also highlight how standardizing report summaries of micro/nanorobotics is essential not only for increasing the quality of research but also for minimizing investment risk in their potential commercialization. We review current patents and commercialization efforts based on emerging proof-of-concept applications. We expect to inspire future research efforts in the field of micro/nanorobotics toward future medical diagnosis and treatment.

Keywords: commercialization; in vivo; medical translational research; microrobot; nanomedicine; nanorobot.

Figure 1

(A) Scheme of medical perspectives in micro/nanorobotics for in vivo human applications, including machines capable of performing biopsy (Gultepe et al., 2012), healing wounds (He et al., 2016), enhanced retention in tissues (Gao et al., 2015), and deliver their cargoes to specific destinations (Felfoul et al., 2016). Analysis of the published articles (see Table 1), including micro/nanorobots for in vivo applications, showing (B) the cumulative number of published articles, and (C) the impact factor of those publications.

Figure 2

Nanorobots for delivery usage. (A) Schematic illustration and SEM of biohybrid nanorobot including a magnetotactic bacteria loaded with liposomes. Reprinted with permission from Taherkhani et al. (2014). Copyright 2014 American Chemical Society. (B) Fluorescent images of transverse tumor sections illustrating the biohybrid robot distribution and population inside the tumor. Reprinted with permission from Felfoul et al. (2016). Copyright 2016 Springer Nature.

Figure 3

Use of microrobots for cell transport and proliferation of cells. (A) SEM images of magnetically actuated nanorobot before and after cell seeding. (B) In vivo fluorescence imaging of HeLa GFP with cells loaded nanorobots illustrating the migration of cells after injection into the right dorsum of the nude mice (Li et al., 2018). Copyright 2018 The American Association for the Advancement of Science.

Figure 4

Use of microrobots for enhanced retention of payloads in the gastrointestinal tract. (A) Schematic illustration of in vivo operation of microrobots in mouse model. (B) Micrograph illustrating the bubble generation at the end of the microorobot responsible for locomotion. Scale bar: 20 μm. (C) Fluorescent images illustrating the gastrointestinal track retention of the dye Rhodamine 6G delivered by the chemically propelled microrobot (i: control, ii: after 6 h, and iii: after 12 h of administration. Reprinted with permission from Li et al. (2016). Copyright 2016 American Chemical Society.

Figure 5

In vivo imaging of magnetically propelled microrobot. (A) Scanning electron microscopy (SEM) (top) and fluorescence images (bottom) of the helical structured microrobot. Schematic of the target in vivo area and magnetic resonance imaging of microrobots inside rats. Illustrating different microrobot concentrations at the (B) subcutaneous tissues and (C) inside the mouse stomach. Reprinted with permission from Yan et al. (2017). Copyright 2017 The American Association for the Advancement of Science.

Figure 6

Overview of micro/nanorobotics intellectual property, as described in section Intellectual Property and Commercialization. (A) Accumulative published patents in the last years. (B) Graph illustrating patents considering the application per year.