Page 24 - ITU Journal Future and evolving technologies Volume 2 (2021), Issue 3 – Internet of Bio-Nano Things for health applications
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ITU Journal on Future and Evolving Technologies, Volume 2 (2021), Issue 3




          transduces information‑encoded electronic input signals   architecture  that  can  enable  the  in  vivo  optical
          into  biologically‑recognized  signals  in  the  form  of  hy‑   stimulation  of  brain  cells  to  control  neuronal
          drogen  peroxide  through  an  oxygen  reduction  reaction.   communications  based  on  external  EM  signals.  Their
          These signals are recognized by bacterial cells that are at‑   device architecture includes a wireless antenna unit that
          tached  to  the  biohybrid  electrode,  and  then  biologically   connects the implanted device to external networks, an
          propagated  across  a  microbial  population  with  quorum   ultrasonic  energy  harvester,  and  a  micro  light  emitting
          sensing molecules.  The overall electronic‑biology link is   diodes (  - LED) for optical stimulation.
          bidirectional such that a microbial subpopulation in the
                                                               Fluorescent  molecules,  such  as    luorescent  proteins,
          BioLAN generates speci ic molecules that can be detected   quantum dots, and organic dyes, can also be used to rea-
          by  the  electrode  via  an  electrochemical  oxidation  reac‑   lize  a  wavelength‑selective  optical  interface.  In  [113],
          tion.                                                organic   dye   molecules   have   been   used   as
          Wearable and epidermal tattoo biosensors and transder‑   nanotransceiver  antennas  for  FRET‑based  molecular
          mal  drug‑delivery  systems,  which  have  attracted  a  sig‑   nanonetworks.  They  act  as  single  molecular  optical
          ni icant research interest for various healthcare applica‑   interfaces  that  receive  optical  control  signals  from  an
          tions,  can  also  be  targeted  for  an  macro‑nano  interface   external  source  and  non‑radiatively  transmit  them
          that can connect intrabody IoBNT to the external commu‑   into  a  FRET‑based  nanonetwork.   They  enable  an
          nication networks, with the integration of communication   nano‑to‑macro  interface  as  well,  since  the  excited
          antennas, such as radio‑frequency‑identi ication (RFID)‑     luorescent  molecules  return  to  their ground  state  by
          tag‑antennas [117, 118, 119, 120].  The challenges lie in   releasing  a  photon  at  a    ic  wave‑length  that  can
          the  further  miniaturization  of  these  devices  as  well  as   be  detected  by  an  external  photodetector.  Similarly, in
          their continuous operation, since biosensors exposed to   [75, 126], it is suggested that a nano‑to‑ macro interface
                                                               can  be  realized  with  engineered  bacteria  receivers
          physiological    luids  suffer  contamination,  and  drug  de‑
                                                               expressing  pH‑sensitive  green   luorescent  proteins
          livery  systems  require  periodic  replenishment  of  their
                                                               (GFPs)  that  change  excitation/emission  characte-ristics
          reservoir.
                                                               depending  on  the  pH  of  the  environment.  Biolumi‑
          3.2.2   Optical Interfaces                           nescent molecules that are excited upon reaction with a
                                                               target molecule can also be used for the direct conversion
                                                               of MC signals to optical signals to enable a nano‑to‑macro
          Light represents an alternative modality to interface the
                                                               interface, as proposed in [127, 108].
          intrabody IoBNT with external networks. In the case that
          MC is utilized in IoBNT, such an optical interface can be
          realized with the help of light‑sensitive proteins and bio‑   3.2.3   Other Interfacing Methods
          luminescent/ luorescent proteins.
          Optical control of excitable cells,  e.g.,  neurons and mus‑   Depending on the communication modality utilized in in‑
          cle cells, can be achieved through a well‑known technique   trabody IoBNT, there are some other nano‑macro inter‑
          called optogenetics [121].  The method relies on the ge‑   facing methods proposed in the literature. For example, in
          netic    ication  of  natural  cells  for  enabling  them  to   [128], the authors consider the use of magnetic nanopar‑
          express light‑sensitive transmembrane ion channel pro‑   ticles (MNs) as information carriers in a MC system. They
          teins, e.g., channelrhodopsin. The resulting light‑sensitive   propose a wearable magnetic nanoparticle detector in the
          ion channels open or close depending on the wavelength   form of a ring to connect the intrabody MC to an RF‑based
          of the incident photons. The technique enables speci icity   backhaul.  In a follow‑up study [129],  they also demon‑
          at the level of single cells in contrast to conventional elec‑   strate the control of MN‑based MC signals in micro luidic
          trical interfacing techniques, which generally suffer from   channels with external magnetic  ields, that could poten‑
          low  level  of    icity.  It  is  shown  in  [122,  123]  that   tially evolve to a bidirectional interface for IoBNT.
          bacteria can also be engineered to express speci ic light‑   In light of the emerging reports on the EM‑based wireless
          sensitive proteins, e.g., bacteriorhodopsin, that pump out   control of cellular functions via speci ic proteins that are
          protons under illumination, and thus, change the pH of its   responsive to electromagnetic  ields [130], a wireless link
          close environment.                                   is proposed to connect THz‑band EM and MC modalities,
          In [56], the authors propose that optical control of engi‑   that can translate into an EM‑based nano‑macro interface
          neered cells with light‑sensitive ion channels can be ex‑   [131].  The authors in [132], develop an information the‑
          ploited to enable an optical macro‑to‑nanoscale interface   oretical model for the mechanotransduction communica‑
          that can modulate the molecular release of MC transmit‑   tion  channel  between  an  implantable  THz  nanoantenna
          ters.  The authors in [124],  experimentally demonstrate   acting as the transmitter and a biological protein as the re‑
          that synthetic bacteria expressing bacteriorhodopsin can   ceiver undergoing a conformational change upon stimula‑
          convert external optical signals to chemical signals in the   tion by the THz waves.  Although THz‑waves are theore-
          form  of  proton  concentration  at  1  bit/min  conversion   tically  shown  to  reliably  control  the  conformational
          rate.  They  use  the  same  technique  to  enable  an  expe‑   states of proteins, it remains as a challenge to investigate
          rimental  MC  testbed  in  [75].  Similarly,  in  [125],  the   the  use  of  the  same  modality  in  sensing  the  protein
          authors  propose  an  implantable  bio‑cyber  interface   states to enable bidirectional wireless interface.




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