Organic–Inorganic Hybrid Perovskite Materials for Ultrasonic Transducer in Medical Diagnosis

Abstract

The ultrasonic transducer is considered the most important component of ultrasound medical instruments, and its key active layer is generally fabricated by piezoelectric materials, such as BaTiO₃, Pb (Zn, Ti)O₃, PVDF, etc. As the star material, perovskite photovoltaic materials (organic and inorganic halide perovskite materials, such as CH₃NH₃PbI₃, CsPbI₃, etc.) have great potential to be widely used in solar cells, LEDs, detectors, and photoelectric and piezoelectric detectors due to their outstanding photoelectric and piezoelectric effects. Herein, we firstly discussed the research progress of commonly used piezoelectric materials and the corresponding piezoelectric effects, the current key scientific status, as well as the current application status in the field of ultrasound medicine. Then, we further explored the current progress of perovskite materials used in piezoelectric-effect devices, and their research difficulties. Finally, we designed an ideal ultrasonic transducer fabricated by perovskite photovoltaic materials and considered the future application prospects of organic and inorganic halide perovskite material in the field of ultrasound.

1. Introduction

Ultrasound (US) is an imaging technology that uses high-frequency sound waves to characterize tissue. Over past decades, due to its non-invasiveness, real-time capabilities, and safety, ultrasonic technology (UT) has been applied in a wide range of medical and related manufactory areas with rapid advancements in transducers, microelectronics, data acquisition, signal processing, and related software fields. Moreover, ultrasound technology continues to evolve additional functions in medical fields [1,2,3,4,5,6], which include 3D ultrasound imaging [1,2,3,4], elastography [5,6,7,8], contrast-enhanced ultrasound (CEU) using microbubbles [9,10,11,12], and wearable ultrasound using stretchable skin-worn phased arrays [13,14].

However, the performance of ultrasound is largely determined by ultrasound transducers, which convert electrical energy into mechanical (sound) energy and back again, based on the piezoelectric effect. An ultrasonic transducer is a special sound-related sensor; piezoelectric electrical signals are sent to the object, and when the signal strikes the object, it then reverts to the transducer. In detail, the ultrasonic transducer is considered a very important core component of the medical ultrasound system, which converts the electrical signal of the system into ultrasonic waves, reflects from the inside of the human body, converts the back signal, and sends it back to the system to form an image. The reason why the transducer is the key to the whole system is because, as is commonly said, “garbage in, garbage out”, the quality of the original signal that the transducer sends back to the system is the “original material” of the final system image. System engineers can use a variety of powerful signal processing algorithms to optimize and shape images, but the quality of the original signal is the most critical basis for improving image quality. Generally, the ultrasound transducer consists of five main components which include matching layers, piezoelectric layers, positive and ground electrodes on the faces of the element, and conductive backing (see in Figure 1) [1,2,3,4,15].

Ultrasound transducer heads used in the clinical practice in current hospitals are basically stacked. The most important material layers are matching layers, piezoelectric layers, and backings. A rubber layer between them is usually used to stick them together, and the front and rear ends of the piezoelectric wafer are connected by metal coatings and cables. The key materials in ultrasound transducers must be piezoelectric wafers. Piezoelectric wafers are a type of crystal material in which the positive and negative charge centers of the lattice are coincident when they are in static equilibrium, so there is no electrical signal output. However, when they are stretched or squeezed by external forces, the positive and negative charge centers of the lattice will deviate from each other, and there will be an electric field formed inside the crystal material. Then, the positive and negative charges will be gathered at the front and back ends of the piezoelectric wafer. Dynamic repeated stretching and extrusion (i.e., mechanical vibration) causes the electric field inside the material to flip repeatedly, creating an alternating current output in front of and behind the piezoelectric wafer, which is named the piezoelectric effect [8,9,10,11,12,13,14,15].

The key fabrication techniques of ultrasonic transducers are the piezoelectric wafers and the matching layers. Piezoelectric wafers are generally polycrystalline precursor materials sintered at high temperatures [15], and the common precursor materials mainly include lead dioxide, lead titanate, lead zirconate, etc., and at the same time, they must go through many processes of post-processing to be truly used in ultrasonic transducers. The role of matching layers and backing materials is increasing response amplitude and reducing response time. The matching layer is generally made by stirring with epoxy resin and adding high-density powder (such as tungsten powder or alumina powder), and for high-impedance matching materials, there are also solid materials such as glass or graphite directly used. A thin, even paste between the matching layers is critical [3,4,15].

The piezoelectric layer is the key layer for ultrasound transducers. Figure 1B gives the development of piezoelectric material milestones/breakthroughs. The piezoelectric effect was first discovered in 1880 by Pierre and Jacques Curie in piezoelectric quartz crystals. In the early 1940s, a breakthrough was achieved by the use of ferroelectrics with a perovskite structure. The first of these ferroelectrics, barium titanate (BaTiO₃) (BT), was discovered independently by Von Hippel and Goldman. The milestone studies, which established the perovskite PZT system as exceptionally suitable piezoelectric material formulations, were carried out by Jaffe et al., who discovered that the nearly temperature-independent morphotropic phase boundary (MPB) in PZT was vitally important for piezoelectric applications, owing to the high piezoelectric properties near the MPB compositions. Figure 1C gives a comparison of the “hard” and “soft” PZT ceramics which have been extensively used for more than 60 years from the 1950s [15]. Different from ferroelectric ceramics/crystals, polyvinylidene fluoride (PVDF) polymers, which were first reported in 1969, are strong candidates for new sensors that cannot be realized with piezoceramics or single crystals. Various piezoelectric composites were introduced by Newnham in 1978, through the concept of “engineered biphasic connectivity”. Systematic studies on the piezoelectric properties of PMN-PT crystals poled along different crystallographic directions were reported in the late 1990s and early 2000s [1,2,3,4,15].

Excitingly, the brightest star of perovskite structure is undoubtedly the organic and inorganic hybrid perovskite represented by CH₃NH₃PbI₃ in the past decade [16,17,18,19]. Since the first report by Miyasaka Research Group of Japan in 2009, the power conversion efficiency of perovskite solar cells has increased significantly from about 3% to more than 25% in less than one decade, stimulating fierce competition around the world [19,20,21,22]. Such perovskite materials have also produced great application prospects in the fields of phototransistors, detectors, laser generation and detection, imaging, hysteresis storage, and so on [16,17,18,19,20,21,22,23,24,25,26].

Due to the unique crystal symmetry and structure of organic and inorganic hybrid perovskites, which are still widely debated, the present perovskite materials exhibit a controllable ultra-sensitive piezoelectric effect and will provide great potential for application in the field of ultrasound. It is generally accepted that CH₃NH₃PbI₃ is a cubic structure at high temperatures and a quad-rank structure at room temperature [17]. There are two more possibilities for spatial groups of quadrilateral structures: one is an I4/mcm structure, which is a centrally symmetrical nonpolar structure; the other is the I4 cm structure, which is a polar structure of non-central symmetry. Unfortunately, the two lattice structures are subtle and difficult to distinguish. Over the past few years, scholars have published numerous papers on X-ray diffraction (XRD), neutron diffraction, optical second harmonic excitation (SHG), macroscopic hysteresis loop testing and pyroelectric testing, microscopic piezoelectric atomic force microscopy (PFM), transmission electron microscopy (TEM), and even density functional theory (DFT) first-principles calculations and molecular dynamics simulations (MD) [15,16,17,18]. However, there is no definite result at present, and opinions are divided. Some studies consider systems to be polar structures, while others consider structures to be nonpolar. These controversies have cast an even more mysterious veil over the structure of organic and inorganic hybrid perovskites.

In 2017, two high-impact papers, which were published in Energy & Environmental Science and Science Advances, both demonstrated very clear and typical domain structures in CH₃NH₃PbI₃ [27,28]. However, the authors interpret it very differently. The German Colsmann group believes that this is a ferroelectric domain, while the Jin-Song Huang group believes that it is an iron bomb domain and a non-ferroelectric domain. Recently, Huang et al. further conducted an in-depth analysis of CH₃NH₃PbI₃ single-crystal domain structure, and they observed the domain structure through polar optical microscopy, scanning electron microscopy, AFM morphology, and PFM. These domains are likely structures formed by variations of the cubic-quadrilateral phase transition [17]. Notably, they found that there are high-response domains and low-response domains for electrogenic positive strains [17].

In this work, we firstly summarize the research progress of commonly used piezoelectric materials and their piezoelectric effects, the current key scientific issues, research difficulties, and the application status in the field of ultrasound medicine. Then, we further summarize the research progress of the piezoelectric effect of perovskite materials, the current key scientific issues and research difficulties, and consider the future application prospects of organic and inorganic perovskite materials in the field of ultrasound.

2. Discussion

Ultrasound technology can widely apply in medicine [8,9,10,11,12,13,14]. Conventional 2D US has been widely used in various clinical applications. However, the limitation of 2D US imaging makes diagnostic accuracy uncertain, as it heavily depends on the experience and knowledge of clinicians. Therefore, 3D ultrasound imaging was proposed to help diagnosticians acquire a full understanding of the spatial anatomic relationship [1,2,3,4]. Figure 2A shows the structure of a mechanical 3D probe. The 3D probe is developed for real-time 3D US imaging by assembling a linear array transducer, which can be rotated by a motor with a computer control [8]. The axis of rotation, tilt, or translation can be used as reference frame for 3D image reconstruction. There are three types of mechanical scanning including linear scanning, tilting scanning, and rotational scanning. A variety of mechanical 3D probes are developed in various clinical applications [8,9,10].

Ultrasound elastography (USE) is an imaging technology sensitive to tissue stiffness that was first described in the 1990s [4,5,6,7,8]. Its elastography-based imaging techniques have received substantial attention in recent years for non-invasive assessment of tissue mechanical properties. Measurements are acquired in specialized imaging modes that can detect tissue stiffness in response to an applied mechanical force (compression or shear wave) [7,8]. In Figure 2B, a normal stress σ is applied to tissue by a static compression with stress ε. Besides strain imaging, shear wave imaging (SWI), a technique in which a dynamic stress ε is applied to tissue with stress ε by using a mechanical vibrating device, is also frequently applied [6,8].

Contrast-enhanced ultrasounds (CEU) were invented for use as an ultrasound contrast agent to enhance image resolution to distinguish vessels clearly and minimize noise and background signals. [10] Many kinds of ultrasound with contrast agents, which are made of lipid, polymer, and protein shells, have been used. For example, Figure 2C shows the therapeutic use of the sonoporation effect of microbubbles [9]. Contrast-enhanced ultrasound stability limitations are caused by diffusion of the core gas across the shell [9,10]. In recent years, studies such as coating microbubbles with nanoparticles, US/MR dual-modal microbubbles, and microbubbles for targeted imaging can enhance the potential to overcome the limitations of microbubbles and extend their applications [11,12].

Wearable ultrasound (WU) is the latest advancement in current ultrasound applications. It is described as stretchable phased arrays for the continuous monitoring of physiological signals from deep tissues, constrained by the depth of signal penetration and by difficulties in resolving signals from specific tissues [13,14]. Figure 2D shows a prototype skin-conformal ultrasonic phased array for the monitoring of hemodynamic signals from tissues up to 14 cm beneath the skin [14].

Therefore, the ultrasound has extended its application in the fields of biomedical, biotechnology, etc.

Antiferroelectric or ferroelectric materials have been always regarded as a promising candidate for electronic energy storage devices, owing to their natural double polarization versus electric field (P−E) hysteresis loops. Recently, the two-dimensional (2D) organic and inorganic hybrid perovskite materials, with structural diversity and tunability, have received a large number of attracted interests [18,25,26]. For example, Wu et al have reported a new type of 2D Ruddlesden−Popper (RP) hybrid perovskite antiferroelectric, ((CH₃)₂CH₂NH₃)2CsPb₂Br₇ showing an above-room-temperature Curie temperature at 353 K, and trigging by the synergistic dynamic motion of inorganic Cs atoms and organic isobutyl ammonium cations [18].

As depicted in Figure 3(Aa), inorganic alkali metal Cs + ions, which are confined in the cavities, constructed by the corner-sharing PbBr₆ octahedra, exhibit distinct shifts along their crystallography b-axis orientation [18]. It is considerably interesting that displacement directions of inorganic Cs⁺ ions in two adjacent layers are antiparallel, which obviously distinguishes itself from previously reported hybrid perovskite. Similar to inorganic Cs + ions, the organic i-BA + moieties’ arrangements in between two adjacent layers are also antiparallel along their b-axis direction [29,30]. Consequently, the combination of dynamic movement of organic and inorganic cations gives rise to antiparallel alignment of adjacent dipoles along their b-axis direction, thereby resulting in macroscopic zero net spontaneous polarization, which suggests the possible antiferroelectricity of (i-BA)₂ CsPb₂Br₇ [18,29,30].

The double hysteresis loop, which is one of most powerful pieces of evidence to ascertain antiferroelectricity, appears when the antiparallel dipoles transform into parallel arrangement along the same direction by applying an adequate external electric field. Figure 3B shows the representative P−E double hysteresis loops over a wide temperature range of 298−353 K at an electric field of 94 kV/cm for (i-BA)₂ CsPb₂Br₇ which was obtained by deducting the normal resistance constituents [18]. At room temperature, 298 K, the (i-BA)₂CsPb₂Br₇ shows a perfect P−E double hysteresis loop, making it much more promising as an application in electronic energy storage cells. The corresponding polarization value is estimated to be 6.3 μC/cm². Such a value is comparable to some other antiferroelectric materials, including 2-trifluoromethylbenzimidazole (5.9 μC/cm²) and 2-difluoromethylbenzimidazole (6 μC/cm²) [31]. Meanwhile, the forward switching field from antiferroelectric to ferroelectric conversion (E_AFE-FE) and the backward switching field from the ferroelectric to the antiferroelectric conversion (E_FE-AFE) were acquired from current peaks of the current I−E curves. From Figure 3(Ab), it can be clearly observed that the values of E_AFE-AFE and E_FE-AFE are 75 and 40 kV/cm, respectively [18]. With an increase in the temperature, the switching field is gradually reductive, which indicates that the electric field inducing the dipoles’ transformation from an antiparallel (antiferroelectric state, AFE) to a parallel arrangement (ferroelectric state, FE) becomes easier at relatively higher temperatures. This phenomenon of the reduced switching electric field is attributed to the flattened free-energy barrier between AFE and FE states with increasing temperature [18,31,32,33].

Many recent works have been made to further enhance the PCEs of perovskite solar cells (PSCs), while the best reported PCE value is now improved over 25.7% [20]. However, further promoting the value of PCEs for PSCs is challenged by their material properties, stability, and series of packaging technologies. Notably, the piezo-phototropic effect has been obtained by a number of photovoltaic scientists [18,28,31]. In Figure 3C, Sun et al. reported a new approach to increase the PCEs of flexible PSCs via introduction of the piezo-phototronic effect in the PSCs by growing an array of ZnO nanowires on flexible plastic substrates, which act as the electron-transport layer for PSCs [16]. From the piezo-phototronic effect, the absolute PCE was improved from 9.3 to 12.8% for flexible perovskite solar cells under a static mechanical strain of 1.88%, with a ∼40% enhancement but no change in the components of materials and device structure [16]. A corresponding working model was proposed to elucidate the strategy to boost the performance of the PSCs [16].

In Figure 3D,E, Li et al. reported the development of nonlinear atomic force microscopy methods to distinguish the relative contributions of iron polarization and ion migration by comparing the electromechanical coupling effects of double frequency [21,34]. They found that, under light, the doubling response increased significantly, the corresponding quality factor was enhanced, and the resonance frequency was slightly reduced, showing the enhanced effect of photo ferrolideanization [21]. The corresponding double-frequency response did not change significantly, indicating that the illumination did not cause significant ion migration. In order to reveal the possible effects of polarization enhancement, the research group further developed the local photocurrent microscopy method, imaging the photocurrent distribution under a series of bias voltages, and reconstructing the JV curve of the nanoscale local area through principal component analysis, and found that the hysteresis was very low, showing that even in the presence of iron polarization, the iron polarization still had no large impact on photovoltaic hysteresis [35,36]. This nanoscale local association has also been confirmed by macroscopic device testing. Therefore, this study shows that we can improve the separation efficiency of its photogenerated carriers through the design of iron polarization, without worrying about its adverse effects on photovoltaic hysteresis [37].

As shown in Figure 4A, Huang et al. reported CH₃NH₃PbI₃ crystals that were self-grown on FTO/TiO₂ substrates. Synchrotron X-ray diffraction (XRD) covering a large surface area on the scale of hundreds of microns, as shown by the profiles of several measured reflections denoted in the pseudo-cubic setting, indicated the single-crystalline nature of CH₃NH₃PbI₃ [18]. High-resolution transmission electron microscopy (HRTEM) was further implemented to reveal the crystallography of single-crystal CH₃NH₃PbI₃, showing a well-ordered crystalline lattice in Figure 4(Ac) [18].

Remarkably, in Figure 4B, the SHO works well for lateral PFM in high-response polar domains but completely fails in low-response nonpolar domains, as indicated by black dots for all failing points in the corrected amplitude mapping (Figure 4(Ba)) that completely cover the low-response domains. In other words, piezo-response in black regions of Figure 4(Bb) yields no valid solution under SHO. It is notable that the mechanisms other than piezoelectricity, such as electrostatic interactions and ionic activities, are highly unlikely to induce lateral piezo-response due to their high structure symmetry [36,38].

In Figure 4(Be,f), it was observed that, for electrogenic positive strains, there are high-response domains and low-response domains. Interestingly, first-order linear effects dominate in high-response domains and second-order nonlinear domains dominate in low-response domains. Further analysis reveals the coexistence of polar and nonpolar domains. As shown in Figure 4(Ba–d), the domain with the high positive strain response has a high shear strain under the appropriate orientation and matches the polarity domain; domain shear strain responses with low positive strain responses are low and match nonpolar domains [38,39].

Based on the current excellent, stable ferroelectric and piezoelectric effects of organic and inorganic halide perovskite materials reported recently, their excellent performance can be applied to the ultrasonic detection active layer, and then play a huge role in application potential in the field of ultrasound medicine. According to the present structure of ultrasonic equipment, we have designed an ideal ultrasonic detector based on organic and inorganic perovskite materials, and look forward to its industrial application in the near future, which is briefly demonstrated in Figure 5.

3. Conclusions and Outlook

In summary, we first summarized the research progress of commonly used piezoelectric materials and their piezoelectric effects, the current key scientific issues, research difficulties, and the application status of ultrasound. Especially, we focused on current device research and application progress of piezoelectric materials in the medical field. Owing to the sensitive piezoelectric or ferroelectric properties, we further summarized the current research on perovskite piezoelectricity, and further designed and proposed its future applications in the field of ultrasound, especially the huge application prospects of ultrasound medicine applications, such as biological and chemical sensors, high-intensity focused ultrasound for medical therapeutics, blood flow rate measurement, and ultrasound imaging [40,41,42,43,44,45,46].

It is well-known that organic–inorganic hybrid perovskite materials exhibit excellent properties and ultra-high sensitivity in piezoelectric effect studies, and the preparation of materials does not require expensive equipment and processes. However, a series of problems in organic–inorganic hybrid perovskite materials, such as the humidity and thermal stability of the material [24,25,26], seriously restrict their industrialization development and application. Therefore, methods to obtain cheap and stable perovskite materials are of great significance for the widespread development of ultrasonic sensors in the future. For example, many research groups in recent years have improved the stability and performance of perovskite materials through series of new strategies such as solvent engineering, additives, and interface and surface passivation modification, which are also worth learning from, in the study of the active layer of ultrasonic sensors.

Author Contributions

Conceptualization, Q.L., L.Y. and Y.Y.; methodology, S.Z., F.W., Y.G. and Y.Y.; formal analysis, L.Y., Y.Y. and S.Z.; writing—original draft preparation, Q.L., L.Y., X.D. and Y.Y.; writing—review and editing, Q.L.; supervision, L.Y., Y.Y. and S.Z.; funding acquisition, S.Z. All authors have read and agreed to the published version of the manuscript.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Figure 1. (A) Structure of a single-unit type matrix transducer. (B) Development of piezoelectric materials with mile-stones/breakthroughs. (C) Comparison of the “hard” and “soft” PZT ceramics. Basic structure of ultrasound transducers and development of the piezoelectric layer material [15]. Adapted with permission from Ref. [15]. Copyright 2018, Springer Nature.

Figure 2. Ultrasound technology applications in medicine. (A) (See in Figure 1 in reference [1] and Figures 2 and 3 in reference [3]. Adapted with permission from Ref. [1]. Copyright 2020, Royal Society of Chemistry) shows the structure of a mechanical 3D probe and 3D ultrasound imaging [3]. Adapted with permission from Ref. [3]. Adapted with permission from Ref. [3]. Copyright 2017, Hindawi. (B) (see in Figure 2 in reference [8], Adapted with permission from Ref. [8]. Copyright 2013, Elsevier) illustrates the before and after static compression of elastography for a medical probe [8]. (C) (see in Figure 4 in reference [9]) shows the contrast-enhanced ultrasound using microbubbles [9]. Adapted with permission from Ref. [9]. Copyright 2017, Springer nature. Application in neck of a wearable ultrasound is shown in (D) (see in Figure 4A,B in reference [14]). Adapted with permission from Ref. [14]. Copyright 2021, Nature.

Figure 3. (A). The crystal structure comparison of (i-BA)2CsPb2Br7 at two different temperatures: (a) antiferroelectric phase (293 K) and (b) paraelectric phase (360 K). All hydrogen atoms were removed for clarity. (B). Antiferroelectric properties and corresponding current signals of (i-BA)2 CsPb2Br7: (a) the electric polarization as a function of the electric field (P-E) hysteresis loops and (b) current versus electric field (I-E) curves for (i-BA)2CsPb2Br7 performed at four different temperatures (298 K, 318 K, 338 K, 358 K) at 40 Hz. (C) Structure of the ZnO-based PSC. Under irradiation, the photoinduced carriers separate at the interface between ZnO NWs and perovskite. The electrons then transport toward the ZnO nanowire. (D) Comparison of piezo response mappings in the dark and under illumination: (a–d) mappings of topography, amplitude, contact resonant frequency, and quality factor in the dark; (e–h) mappings of topography, amplitude, contact resonant frequency, and quality factor under light illumination. (E) Comparison of the first polarization strain and second harmonic ionic strain versus excitation voltage in the dark and under illumination. [16,18,21]. Reprinted/adapted with permission from Refs. [16,18,21].

Figure 4. (A). Single-crystalline CH3NH3PbI3 directly grown on FTO/TiO2 substrates: (a) top view SEM image; (b) selected reflections from synchrotron XRD integrated over a rocking angle range of 1 degree; and (c) HRTEM image with the corresponding selected area’s electron diffraction pattern as inset. (B). Alternating polar and nonpolar domains in CH3NH3PbI3 crystal: (a) Lateral PFM mapping showing complete failure of SHO (marked by black dots) in nonpolar domains due to their lack of true piezoelectricity; (b) Vertical PFM mappings showing identical domain pattern consisting of high-response polar domains and low-response nonpolar domains; (c) Resonant frequency mapping of vertical PFM showing elastic contrast between polar and nonpolar domains and good resonance tracking; (d) Quality factor mapping showing substantially lower quality factor and, thus, higher energy dissipation in nonpolar domains; (e) Point-wise tuning of piezo-response vs. frequency showing a point in high-response polar domain has dominant first harmonic response and negligible second harmonic one, while a point in low-response nonpolar domain has higher second harmonic response; and (f) Comparison of first and second harmonic responses [18].

Figure 5. (A) Ideal ultrasonic detector based on organic and inorganic perovskite materials. (B) The proposed ultrasonic probe in the future based-on organic-inorganic hybrid perovskite materials.

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