Comprehensive biocompatibility of nontoxic and high-output flexible energy harvester using lead-free piezoceramic thin film

Flexible piezoelectric energy harvesters have been regarded as an overarching candidate for achieving self-powered electronic systems for environmental sensors and biomedical devices using the self-sufficient electrical energy. In this research, we realize a flexible high-output and lead-free piezoelectric energy harvester by using the aerosol deposition method and the laser lift-off process. We also investigated the comprehensive biocompatibility of the lead-free piezoceramic device using ex-vivo ionic elusion and in vivo bioimplantation, as well as in vitro cell proliferation and histologic inspection. The fabricated LiNbO3-doped (K,Na)NbO3 (KNN) thin film-based flexible energy harvester exhibited an outstanding piezoresponse, and average output performance of an open-circuit voltage of ∼130 V and a short-circuit current of ∼1.3 μ A under normal bending and release deformation, which is the best record among previously reported flexible lead-free piezoelectric energy harvesters. Although both the KNN an...

2][23] Several researchers have reported that PZT might be used for biological and in vivo applications, but these reports were only based on cell viability or histology over shortterm periods, 18,24,25 which cannot guarantee actual biocompatibility for long-term periods or repeated exposures. 26Pb causes severe chronic poisoning and pain with long-term exposure (years-to-decades), even when accumulated in small traces. 27,28Additionally, compounds containing Pb, e.g., lead oxides, are also classified as hazardous materials because they have been implicated in diverse diseases, including tumors. 29,30][36][37] Piezoelectric polymers (e.g., polyvinylidene fluoride (PVDF)) are alternative materials for piezoelectric-bionic applications because they are soft and flexible as previously reported bioimplantations, 38,39 but they have relatively weak chemical/mechanical resistivity, and mediocre piezoelectric coupling compared to piezoelectric ceramics. 40Recently, numerous researchers have investigated high-performance lead-free piezoelectric ceramics with perovskite-crystalline structures such as BaTiO 3 , 41,42 (Bi,Na)TiO 3 , 43 and BiFeO 3 -based ceramics. 44Although they are alternatives to leadbased piezoceramics, there are diverse shortcomings, such as the low Curie points, the poor piezoelectric coefficients, and the serious leakage levels.][47][48][49][50][51][52] Nevertheless, the deposition or post-crystallization of KNN-based materials involves difficult processing due to the loss of vaporizable alkaline compositions and slow deposition rates. 53,54][56] Herein, we demonstrate a high-performance KNN-based flexible piezoelectric energy harvester (f-PEH) using the ADM with the laser lift-off (LLO) process and investigate overall biocompatibility features (Fig. 1).This lead-free f-PEH produces high generating-output of ∼130 V and ∼1.3 µA from bending motions; these values reach ∼170 V and ∼5.5 µA using random finger flicks.Our developed f-PEH represents the best performance of lead-free f-PEHs, and it is even comparable to previously reported lead-based f-PEHs.We also conducted experiments of cell viability and histological stability to show the short-term biocompatibility of both KNN and PZT.To prove the comprehensive biocompatibility of piezoceramics, general elution tests detecting dissolved ions were additionally performed to foresee long-term toxicity.Finally, we confirmed the electrical output of our high-performance nontoxic f-PEH in in vivo circumstance, conformally sutured and deformed on a porcine heart, to show its bioimplantable feasibility.
Fig. 2(a) shows the fabrication of the KNN-based f-PEH device using the ADM and LLO.As shown in the scanning electron microscopy (SEM) image of Fig. 2(b), we synthesized 0.058LiNbO 3 -0.942(K0.480 Na 0.535 )NbO 3 (L-KNN) using the solid-state method for excellent piezoelectricity. 49,57he tunneling electron microscopy (TEM) image and the fast-Fourier transformation (FFT) indicate the perovskite L-KNN particles (the right panel of Fig. 2(b)). 58After granulation of the particles to ensure high efficiency in the ADM, the powders were blended with O 2 gas to build aerosol flows to be directed onto a sapphire wafer.The aerosol flow was accelerated and ejected from a nozzle (Fig. 2 and consequently, a dense L-KNN thin film was deposited by the mechanical collision of the granule spray in vacuum (GSV), 56 with ∼2.7 µm thickness (Fig. 2(c)) after following post-annealing (800 • C, 1 h).SEM and atomic force microscopy (AFM) images of the as-deposited L-KNN film are also shown in Fig. S1.
To transfer the L-KNN film onto a flexible plastic sheet (∼125 µm thickness), the LLO process was applied to the lead-free piezoelectric film on the sapphire using a XeCl-pulsed excimer laser (Fig. 2(a)).In contrast to sapphire, the L-KNN film absorbs the incident energy since the KNN-based ceramic band-gap energy is lower than the laser photonic energy, 59,60 and this results in meltingdissociation of L-KNN at the interface, followed by the transfer of the L-KNN film from sapphire to the pre-attached flexible plastics (the right panel of Fig. 2(c)).][56] Both Raman spectra before and after the LLO clearly manifest the tetragonal/orthorhombic symmetries of L-KNN maintained during the LLO process, 58 and high crystallinity was confirmed by X-ray diffraction (XRD) patterns (Figs.S2(a) and S2(b)).The chemical composition of the L-KNN film was also retained during the LLO transfer, as demonstrated in the X-ray photoelectron spectroscopy (XPS) (Fig. S2(c)), revealing the advantage of ADM for depositing vaporizable-elemental films.The optical microscope image in Fig. S2(d) shows the overall surface morphology of the transferred L-KNN thin film after the LLO, including slightly overlapping square-shaped laser tracks (beam size ∼625 µm × 625 µm).As shown in Fig. S2(d) and Fig. S3, the more the laser shots were overlapped, the more bubble-like nanoscale ridged agglomerates arose on the laser-irradiated surface.This topographical phenomenon results from laser-induced local melting/dissociation during the short energy-duration irradiation of the pulsed laser (<30 ns). 11,61In the LLO process, namely, there was neither mechanical damage nor chemical degradation for the transfer of the entire area of the L-KNN film onto the flexible polymer sheet.
Fig. 3(a) shows a lead-free f-PEH device made from the KNN-based film.The gold interdigitated electrodes (IDEs), with a 200 µm gap-and-width pitch, were fabricated by photolithography.The bottom inset of Fig. 3(a) provides the results of a three-dimensional (3D) finite element analysis (FEA) simulation, with confirmed physics, 46,49,57,62,63 which indicates the efficient piezopotential of the L-KNN between a pair of IDEs when subjected to bending with a bending radius of ∼1.8 cm (tensile strain of ∼0.25%,rate of ∼2.2% s 1 , and frequency of ∼0.4 Hz).The polarization-electric field (P-E) curve of the L-KNN film energy harvester also exhibited definite ferroelectric behavior (Fig. S4(a)), comparable to that of a previously reported AD-formed PZT film, considering different thickness factors. 55s displayed in the second downward peak of Fig. 3(b), the KNN-based f-PEH generated maximum signals up to 140 V and 1.8 µA during reciprocating bending/unbending with a strain of ∼0.25%.The produced electrical energy was definitively ascribed to the piezoelectric effect of the L-KNN film, as verified by a polarity switching with forward/reverse connections (Fig. S4(b)).Our lead-free energy harvester also showed good mechanical endurance during the durability test with over 6000 cycles and 1 week-strained status (Fig. S4(c)).There is no mechanical crack after repetitive bending (Fig. S5).The voltage output through the circuit load gradually augmented with ascending resistance in the gross (Fig. S4(d)).From changing circuit resistance, a maximum instantaneous power of ∼30 µW was elicited at ∼150 MΩ.Although this matching impedance was too high to be compared with conventional electronic components, due to the high internal resistance of the IDE-type piezoelectric devices, 64 our result demonstrates that lead-free piezoceramics can replace lead-based piezoelectric energy harvesters, even for mechanically flexible manner.Furthermore, the KNN-based f-PEH produced even higher output with finger flicking (time interval of ∼4 s, approximately), up to ∼170 V and ∼5.5 µA, and operated 40 light-emitting diodes (LEDs) with diverse colors (Fig. S4(d)).onto flexible plastics, but the output was low since it could not be crystallized (amorphous KNN, a-KNN) below 300 • C. 51 Although Gao et al. fabricated a decent-performance flexible nanogenerator using patterned/aligned KNN-elastomer composites, the device was too thick (∼200 µm) to achieve efficient mechanical flexibility and high output density. 52On the contrary, our AD-formed KNN f-PEH device is strikingly superior to these representative previous reports of flexible lead-free generators.The high performance in this work is even comparable to that of prior high-performance lead-based f-PEHs made by sol-gel PZT films, 11,65 AD-formed PZT thick film, 55 and solid-grown Pb(Mg 1/3 Nb 2/3 )O 3 -PZT (PMN-PZT) thick film 66 with IDEs under similar deformations.This remarkable output performance of our lead-free f-PEH stems from the high-quality and dense AD-formed L-KNN piezoceramic thin film.

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Jeong et al.APL Mater.5, 074102 (2017)   We subsequently performed cell growth and tissue implant experiments using both AD-formed KNN and PZT films to study cytotoxicity and histotoxicity.Figs.4(a) and 4(b) present the results of cell viability tests of human embryonic kidney (HEK)-293 cells well cultured on KNN and PZT devices like control groups (Fig. S6), respectively, which shows that neither of the piezoceramics are cytotoxic for short-term periods.No species or cell specificity was observed, as evident from H9C2 cell line (rat's cardiomyocyte) also well proliferating on both ceramics, on a par with the control group (Fig. S6).
Cell attachability on both KNN and PZT films was evaluated by culturing the MG-63 (human osteosarcoma) cell.The osteocyte adhered well to both the piezoceramic surfaces without significant biological degradation (Figs.S7(a) and S7(b)).Based on the diverse cell growth, average cell proliferation ratios were calculated for both KNN and PZT devices, which determined that the cells well lived in all cases (Fig. S7(c From the above biocompatibility tests with cellular/histological approaches, it appears that leadbased piezoceramics like PZT, as well as alkaline-based lead-free piezoceramics like KNN, are biocompatible, as contended by several engineers. 18,248][69] In addition, histological inflammation and infection do not easily occur with sterilized extraneous objects without the involvement of germs, viruses, or macroscopic stabs. The best way to realistically examine biocompatibility is with long-term follow up surveys to reveal chronological trends in body fluids and clinical effects after implanting devices into the body; but this is very hard to perform at the laboratory level.In lieu of the actual long-term diagnostic analyses, therefore, we studied the dissolution of PZT and L-KNN films in not only human serum but also tap water, using an inductively coupled plasma mass spectrometer (ICP-MS) to investigate heavy metal ion concentrations eluted from the devices.The temperatures of the human serum and tap water were maintained at about 36.5 • C and 25 • C, respectively, agitated by shaking and stirring, to create close to real conditions.We selected Nb and Pb ions as the primary elements for this ion detection test of KNN and PZT, respectively.Note that Nb is basically considered to be a nontoxic element 70 although there is a report about the harmfulness of Nb dust, 71 which is not the chemical maleficence of Nb.The left panel of Fig. 5 highlights that the eluted Pb concentration from the PZT is about three orders of magnitude higher than the Nb concentration from the KNN in both serum  and water cases.37]72,73 These dissolution results are reasonable because lead oxides are readily soluble in aqueous conditions, 74 while niobium oxides are theoretically insoluble. 75Note that the amount of dissolution in human serum was much higher than the amount in water owing to enhanced corrosive interactions with proteins. 76,77Control tests conducted without devices are plotted in the supplementary material (Fig. S8).
We finally demonstrated the in vivo implantation of our lead-free piezoelectric energy harvester into a porcine chest.As given in Fig. 5 (the middle panel), the KNN-based nontoxic high-output f-PEH was intimately fixed to the living porcine heart by suturing.Our lead-free f-PEH converted the continuous heartbeat biomechanical energy into electrical energy of up to 5 V and 700 nA (Fig. 5, the right panel), which comparable to in vivo PZT-ribbons-array f-PEH. 18Our result is the first to show the bioimplantation of a lead-free f-PEH with high performance in a large-animal model.
To sum up, a high-performance lead-free f-PEH was accomplished using a flexible KNN-based piezoceramic film enabled by the ADM and LLO processing.The lead-free f-PEH generated ∼130 V and ∼1.3 µA with regular bending and 170 V and 5.5 µA with random flicking, which is the best output performance among previously reported lead-free f-PEHs.This result is even comparable to up-to-date lead-based flexible piezoelectric generators.Both AD-formed KNN and PZT showed good short-term biocompatibility as determined by cell and histological studies.Because these approaches do not provide proper information for clinicians, however, we additionally performed ion elution tests of KNN and PZT in both human serum and tap water to chase dissolved heavy metal ions, which can affect physiological phenomena, even in infinitesimal amounts, with long-term accumulation.The resulting concentration of eluted noxious Pb ions measured in the test was meaningful for evaluating the hazardous potential of lead-based piezoceramics for medical/environmental devices.Although the elution test is an indirect approach for determining clinical toxicity, it can provide crucial information about poisoning related to long-term bio-/eco-compatibility.Finally, we confirmed the bioimplantation of our KNN-based f-PEH using a large-animal model.By harnessing the movement of living porcine heart, the sutured nontoxic high-output f-PEH produced electricity of up to 5 V and 700 nA.This work demonstrates the promise of high-performance lead-free piezoelectric energy harvesting for biocompatible and ecofriendly applications, as notable alternatives to lead-based piezoceramics.
FIG. 1. Scheme illustrating the biocompatibility of our high-output lead-free KNN-based f-PEH.

FIG. 2 .
FIG. 2. (a) Schematics of the ADM and LLO.Inset: SEM image of L-KNN granules (scale bar: 100 µm).(b) SEM image (left), and high-resolution TEM image and FFT pattern (right) of a L-KNN particle.(c) Photographs of the as-deposited L-KNN film on a sapphire wafer (left) and the L-KNN film transferred onto a flexible PET (right); bottom figures are cross-sectional SEM images (scale bars: 2 µm).

Fig. 3 (
c) is a plot depicting the output performance levels of previously reported representative f-PEHs including both lead-based and lead-free (KNN-based) piezoceramic devices, compared to this study.Recently, Kim et al. reported a KNN thin film f-PEH using direct sputtering deposition

FIG. 3 .
FIG. 3. (a) Photograph of the L-KNN film f-PEH.Insets: optical micrograph of partial IDEs (top) and 3D-FEA simulation of f-PEH.(b) Voltage and current from the lead-free f-PEH.(c) Comparison between this study and previous studies.
)).The right panels of Figs.4(a) and 4(b) show the optical micrographs of rat's muscular tissue after implanting both piezoceramics into the living rat's thigh for one week, showing no serious histological inflammation, similar to the control tests (Figs.S7(d) and S7(e)).

FIG. 4 .
FIG. 4. Fluorescent confocal images of HEK-293 cells cultured on and histological image after implantation of (a) L-KNN and (b) PZT films.Insets: Confocal images of H9C2 cells.

FIG. 5 .
FIG. 5. Concentration of Nb and Pb ions eluted from L-KNN and PZT films (left).In vivo L-KNN film f-PEH sutured on a porcine heart (middle).Original porcine electrocardiogram (ECG), in vivo generated energy harvesting voltage and current (right).Note that the peak deviation in current was due to the individually different periodic movements of ECG.
FIG. S1.Top-view SEM image of AD-formed KNN thin film and corresponding AFM image