Medical Micro/Nanorobots in Precision Medicine

Abstract

Advances in medical robots promise to improve modern medicine and the quality of life. Miniaturization of these robotic platforms has led to numerous applications that leverages precision medicine. In this review, the current trends of medical micro and nanorobotics for therapy, surgery, diagnosis, and medical imaging are discussed. The use of micro and nanorobots in precision medicine still faces technical, regulatory, and market challenges for their widespread use in clinical settings. Nevertheless, recent translations from proof of concept to in vivo studies demonstrate their potential toward precision medicine.

Keywords: diagnosis; medical imaging; micro/nanorobots; microsurgery; precision medicine; targeted delivery.

Figure 1

Schematic of the current trends of micro/nanorobotics in precision medicine, including delivery, surgery, diagnosis, and medical imaging applications.

Figure 2

Powering mechanism for micro/nanorobots. a) Magnetically propelled microrobot based on rotating microcoil. Reproduced with permission.^{[ 82 ]} Copyright 2012, Wiley. b) Ultrasound propelled microrobot powered by cavitating microbubble. Reproduced with permission.^{[ 94 ]} Copyright 2019, AAAS. c) Chemically propelled motor based on zinc microtube, the microrobot converts gastric fluid into gas bubbles that generate propulsion trust. Reproduced with permission.^{[ 111 ]} Copyright 2015, American Chemical Society. d) Biohybrid microrobot based on the integration of a sperm with a synthetic structure. Reproduced with permission.^{[ 129 ]} Copyright 2018, American Chemical Society.

Figure 3

Micro/nanorobot based delivery of pharmaceuticals. a) Ultrasound propelled nanowires for near‐IR triggered delivery of doxorubicin. Reproduced with permission.^{[ 156 ]} Copyright 2014, Wiley. b) Magnesium powered microrobot for stomach pH neutralization and sustain drug release. Reproduced with permission.^{[ 172 ]} Copyright 2017, Wiley. c) Biohybrid micromotor consisting of a magneto‐tactic bacterium transporting liposomes. Reproduced with permission.^{[ 190 ]} Copyright 2016, Springer Nature. d) Magnetically powered microrotor with enzymatic biodegradation for triggered drug release. Reproduced with permission.^{[ 197 ]} Copyright 2018, Wiley.

Figure 4

Micro/nanorobot based delivery of biologics and genes. a) CaCO₃ powered microrobot for the enhanced delivery of thrombin through flowing blood and halt hemorrhage. Reproduced with permission.^{[ 206 ]} Copyright 2015, AAAS. b) Accelerated catalytic reactivity of tissue plasminogen activator (t‐PA) mediated blood clot degradation by magnetically powered microrobots. Reproduced with permission.^{[ 211 ]} Copyright 2014, American Chemical Society. c) Use of magnesium powered microengines to deliver virus vaccines in a mouse tumor model. Reproduced with permission.^{[ 216 ]} Copyright 2020, Wiley. d) Sperm driven microrobot for heparin delivery capable of going against the flow. Reproduced with permission.^{[ 219 ]} Copyright 2020, American Chemical Society.

Figure 5

Use of microrobots as a scaffold for cell transport. a) Microrobot carrier with programable surfaces to control cell differentiation. Reproduced with permission.^{[ 223 ]} Copyright 2019, Wiley. b) Neuron loaded microhelix robot for brain delivery. Reproduced with permission.^{[ 230 ]} Copyright 2019, AAAS. c) Adipose‐derived tissue loaded microrobot for knee cartilage regeneration. Reproduced with permission.^{[ 231 ]} Copyright 2020, AAAS.

Figure 6

Microrobot as carrier of individual cells. a) Chemically powered microrobot transporting macrophage attached via electrostatic interactions. Reproduced with permission.^{[ 232 ]} Copyright 2019, Wiley. b) Biohybrid microrobot transporting red blood cell. Reproduced with permission.^{[ 233 ]} Copyright 2018, AAAS. c) Magnetically powered microhelix transporting sperm cell. Reproduced with permission.^{[ 235 ]} Copyright 2016, American Chemical Society.

Figure 7

Micro/nanorobot based delivery of inorganic agents. a) Magnetically propelled microrobot for hyperthermia (magnetic heating) therapy. Reproduced with permission.^{[ 240 ]} Copyright 2019, Wiley. b) Photothermal micromotor based wound healing. Reproduced with permission.^{[ 243 ]} Copyright 2016, Wiley. c) Magnetically propelled nanorobot for chemo‐photothermal therapy. Reproduced with permission.^{[ 244 ]} Copyright 2019, American Chemical Society. d) Chemically propelled micromotor for mineral delivery. Reproduced with permission.^{[ 247 ]} Copyright 2019, American Chemical Society.

Figure 8

Microrobot based biopsy and sampling. a) Star‐shaped griper collecting tissue. Reproduced with permission.^{[ 257 ]} Copyright 2015, American Chemical Society. b) Star gripper collecting red blood cells. Reproduced with permission.^{[ 259 ]} Copyright 2014, Wiley. c) Motile microtrap collecting pathogens. Reproduced with permission.^{[ 253 ]}Copyright 2020, Wiley.

Figure 9

Micro/nanorobots for tissue penetration. a) Magnetic microdriller internalizing into liver tissue. Reproduced with permission.^{[ 273 ]} Copyright 2013, The Royal Society of Chemistry. b) Magnetic microdriller penetrating mucin gel. Reproduced with permission.^{[ 274 ]} Copyright 2015, AAAS. c) Magnetic microdriller mobbing inside the eye. Reproduced with permission.^{[ 277 ]} Copyright 2018, AAAS. d) Ultrasound powered microbullet for tissue penetration and cleaving. Reproduced with permission.^{[ 91 ]} Copyright 2012, Wiley.

Figure 10

Micro/nanorobot based intracellular internalization. a) Ultrasound microrobot delivery of miRNA. Reproduced with permission.^{[ 289 ]} Copyright 2015, American Chemical Society. b) NIR powered nanorobot for intracellular delivery. Reproduced with permission.^{[ 297 ]} Copyright 2020, Elsevier. c) Magnetic microspear delivering plasmids into cell. Reproduced with permission.^{[ 300 ]} Copyright 2019, American Chemical Society. d) Urchin‐like microperforator for intracellular payload delivery. Reproduced with permission.^{[ 301 ]} Copyright 2020, Wiley.

Figure 11

Biofilm degradation. a) Urea‐powered micromotor for degradation of cancer spheroids. Reproduced with permission.^{[ 309 ]} Copyright 2019, American Chemical Society. b) Magnetic micromotor for catalytic biofilm degradation. Reproduced with permission.^{[ 310 ]} Copyright 2019, AAAS.

Figure 12

Micro/nanorobot for biosensing. a) Fluorescent sensor for pH monitoring of the surrounding microenvironment using a FRET‐labeled triplex DNA‐based motor. Reproduced with permission.^{[ 312 ]} Copyright 2019, American Chemical Society. b) Micromotor with oligonucleotide probes for detection of complementary nucleic strains. Reproduced with permission.^{[ 314 ]} Copyright 2011, American Chemical Society. c) Loop‐mediated isothermal amplification for motion‐based sensing. Reproduced with permission.^{[ 316 ]} Copyright 2018, Springer Nature. d) Zika virus detection based on motion‐based immunoassay. Reproduced with permission.^{[ 327 ]} Copyright 2018, American Chemical Society.

Figure 13

Micro/nanorobot based isolation. a) Microrobot functionalized with antibodies to isolate target bacteria. Reproduced with permission.^{[ 345 ]} Copyright 2012, American Chemical Society. b) Noncontact manipulation of cancer cells using rotating microrobots. Reproduced with permission.^{[ 352 ]} Copyright 2018, American Chemical Society. c) Red blood cell/platelet coated nanorobot for synergistic isolation of pathogens and toxins. Reproduced with permission.^{[ 358 ]} Copyright 2018, AAAS.

Figure 14

Micro/nanorobots as mechanical probes. a) Nanorobot of measuring intracellular mechanical properties. Reproduced with permission.^{[ 359 ]} Copyright 2018, Wiley. b) Nanorobot for biofluid rheology. Reproduced with permission.^{[ 364 ]} Copyright 2016, American Chemical Society. c) Nanorobot for measuring mechanical forces of a macrophage. Reproduced with permission.^{[ 369 ]} Copyright 2017, AAAS.

Figure 15

Medical imaging of microrobots. a) In vivo fluorescence imaging of magnetically driven microrobot carrying cells into a mouse flank. Reproduced with permission.^{[ 229 ]} Copyright 2018, AAAS. b) In vivo photoacoustic imaging of a magnesium propelled motor located at a mouse intestine. Reproduced with permission.^{[ 382 ]} Copyright 2013, Elsevier. c) In vitro ultrasound imaging detecting bubbles generated by a chemically propelled microrobot. Reproduced with permission.^{[ 382 ]} Copyright 2019, AAAS.

Figure 16

Other medical imaging applications. a) Magnetic resonance imaging of helical micromotors for intragastric region Reproduced with permission.^{[ 377 ]} Copyright 2017, AAAS. b) Radionucleotide based imaging of microrocket coated with iodine isotope. Reproduced with permission.^{[ 386 ]} Copyright 2018, American Chemical Society.

Figure 17

Biofabrication of microrobots and cellular microstructures. a) Hydrogel robot fabricated by magnetic assembly. Reproduced with permission.^{[ 225 ]} Copyright 2014, Springer Nature. b) Tunable fabrication of cellular microstructures using magnetic levitation. Reproduced with permission.^{[ 402 ]} Copyright 2018, Wiley. c) Bioacoustic fabrication of organoids. Reproduced with permission.^{[ 409 ]} Copyright 2015, Wiley.

Figure 18

Micro/nanorobots’ clinical translation outlook. a) Operation of micro/nanorobots in diverse regions of the body. b) Characterization of medical micro/nanorobots based on their potential and ease of deployment. c) Developmental trends of emerging technologies.