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3D Printed Electronic Patch for pH and Hydration Sensing
               There  has been  some  work done  in  fabricating   of stress, and the shape was used to fabricate the wound
           pH-sensing  wound  patches  based  on  fibre  optics ,   patch in this work.
                                                        [29]
           ion-sensitive  field-effect  transistor , nuclear  magnetic
                                        [30]
           resonance , Ultraviolet-visible spectroscopy [32,33] , near-  2.2. Fabrication of patch
                   [31]
           infrared spectroscopy , Raman spectroscopy [35,36] ,   Firstly, the substrate was fabricated  according  to the
                              [34]
           potentiometric  sensor , pH-responsive dyes and     stimulated design. For this purpose, polydimethylsiloxane
                              [37]
           quantum dots [38-48] . Despite the efforts, there are limitations   (PDMS)  (Sylgard 184, DOW, Diatom,  Denmark) was
           of reliability, limited pH range, low sensitivity, complex   used and mixed with a curing agent (10:1 ratio) to give a
           design,  autofluorescence,  use  of  toxic  dyes,  and  high   solution with viscosity ~3.5 Pa.s. To adjust the viscosity
           production cost. Therefore, there exists a need to develop   of the solution, silicon dioxide nanoparticles (SiO  NPs)
           an easy-to-apply, non-toxic and low-cost system, which   (5 – 20 nm, Merck Life Science, Denmark) were added
                                                                                                         2
           can  quantify  both  wound exudate  and  pH levels  in  a   in different ratios (Figure S2). The mixture was heated
           wound.                                              at 80°C for 10  min to get a homogenous solution.  To
               This work demonstrates the potential of flexible and   remove trapped air and bubbles, solution was centrifuged
           printed electronics for integrated wound monitoring by   at 6000 rpm for 10 min followed by degassing at 50°C.
           engineering an on-skin platform. The approach adopted   The patch was printed using Celllink’s BIOX bioprinter
           in this work  was based on the development  of printed   with a mixture containing  20 wt% NPs. Substrate  and
           on-skin sensor patch, which can provide a simple result   top layer were printed using nozzle size and pressure of
           for  the  pH  of  the  wound  fluid.  Single-walled  carbon   22 G, 110 kPa and 25 G, 190 kPa, respectively, and a
           nanotubes (SWCNT) were used for pH sensing owing    speed of 8 mm/s. Ag ink (Smart Fabric Ink tc-c4007, TC)
           to their excellent sensitivity. In earlier  reported  work,   was  used for printing electrodes and hydration sensor.
           a  composite  of carbon  nanotubes (CNT) conductive   Printing was performed using nozzle size of 25 G with
           polymers  were  used  to  increase  the  sensitivity  but   speed and pressure of 5 mm/s and 200 kPa, respectively.
           required the use of reference electrode, which is known to   The temperature of printbed was kept at 60°C. The pH
           suffer from leakage of electrolyte [49,50] . Here, the change   sensor was fabricated by printing SWCNT aqueous ink,
           in CNT resistance is measured as a function of H  ion   (0.2  mg/mL, Merck Life Science, Denmark) using an
                                                      +
           concentration  without the requirement  for a reference   inkjet  printhead. A  total  of  30 layers  were  printed  for
           electrode [51,52] . The patches are also capable of stimulating   homogeneity and interconnection between SWCNTs with
           the wound electrically  for direct  wound management   a speed and pressure of 8 mm/s and 13 kPa, respectively.
           using hydration sensing mechanism.  Fabricated      Valve  open  and  cycle  time  was 1  ms and  100 ms,
           multifunctional  patches show satisfactory  repeatability,   respectively. The temperature of the printbed was kept as
           reusability, and response performance.  To the  authors   60°C with a curing time of 60 s. The complete fabrication
           knowledge, this is the first report on combining the two   process is depicted in Figure 1.
           functionalities of pH and hydration sensing in a single   The complete  patches were designed with four
           patch for wound management. We have used the printing   printed  layers  of  PDMS  modified  with  SiO  NPs  as
           route to fabricate the wound patch due to its attractive   substrate material  and commercial  Ag and SWCNT
                                                                                                      2
           features of low cost, material saving, and fast processing.   inks (Figure 1H). Components 1-4 and 6 were printed
           Printed technologies are a fast-growing area with many   and collectively called as patch while components five,
           techniques under its umbrella namely, material  jetting,   seven, and eight were used as attachments to carry out
           vat polymerization, and material  extrusion [53-55] . We   the  measurements  without  interfering  with  the  printed
           have chosen material extrusion as the preferred mode of
           printing due to the range of the viscosity of the materials   parts. Top insulated layer (1 of Figure 1H) was designed
           used in this work. Material extrusion is also promising to   to support the structure. The presence of three pockets
           create planar platforms with multi-material printing.  allows easy access of fluid for pH and hydration sensors
                                                               (2 and 4 of Figure 1H).
           2. Materials and methods                            2.3. Resistance detection in buffer solution with
           2.1. Finite element analysis (FEA) simulation       different pH

           Solidworks 2019 – 2020 student edition  was used for   Patches  were  tested  in  a  buffer  solution  (McIlvaine
           the simulations of all models (Figure S1). Same forces   buffer,  Merck  Life  Science)  and  resistance  change
           and  fixtures  were  applied  to  all  models.  Patches  were   was measured with a digital Keithley model 2110. The
           subjected  to  forces  in  two directions:  horizontal  and   sensor output was recorded using Kickstart (version 2.4)
           vertical, as marked by yellow and green colored bars. It   software. The sampling rate was 1 kHz, and the data was
           was found that the patch type II has the largest reduction   reviewed with the software KickStart 2.  The patches


           42                          International Journal of Bioprinting (2022)–Volume 8, Issue 1
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