Artificial Tongue Research Articles

A first-of-its-kind 3D biomimetic artificial mouth capable of reproducing the oral processing of soft foods

With a growing global population and ageing demographics, the food industry stands at a pivotal crossroads, necessitating bespoke solutions and groundbreaking innovations. In vitro experiments can help understanding food oral processing and formulating products meeting the specific needs of different populations. However, current in vitro models do not reproduce well human oral anatomy and tongue biomechanics, essential for assessing the behaviour of novel and texturized foods under physiologically relevant oral conditions. In response, we unveil a novel 3D biomimetic artificial mouth, showcasing a pneumatic multi-degree-of-freedom artificial tongue meticulously crafted to mirror the mechanical properties and wettability of the human tongue. This cutting-edge technology, featuring tongue surface papillae, is capable of performing lifelike movements. The comparison with in vivo data demonstrates that it accurately reproduces oral processing of three, vastly different, soft foods. Textural characteristics (firmness, adhesive and cohesive properties) and shear viscosities—measured at oral and oropharyngeal-relevant shear rates—of in vitro food boli closely mirrored those observed in vivo. This in vitro device presents unprecedented opportunities for studying the dynamics of food transformation in the mouth, to adapt texture towards food that can be swallowed with ease and to improve food palatability, accommodating specific health needs critical for older adults (e.g., reduced salivary secretion, tongue weakness or poor coordination).

Artificial Q-Grader: Machine Learning-Enabled Intelligent Olfactory and Gustatory Sensing System.

Portable and personalized artificial intelligence (AI)-driven sensors mimicking human olfactory and gustatory systems have immense potential for the large-scale deployment and autonomous monitoring systems of Internet of Things (IoT) devices. In this study, an artificial Q-grader comprising surface-engineered zinc oxide (ZnO) thin films is developed as the artificial nose, tongue, and AI-based statistical data analysis as the artificial brain for identifying both aroma and flavor chemicals in coffee beans. A poly(vinylidene fluoride-co-hexafluoropropylene)/ZnO thin film transistor (TFT)-based liquid sensor is the artificial tongue, and an Au, Ag, or Pd nanoparticles/ZnO nanohybrid gas sensor is the artificial nose. In order to classify the flavor of coffee beans (acetic acid (sourness), ethyl butyrate and 2-furanmethanol (sweetness), caffeine (bitterness)) and the origin of coffee beans (Papua New Guinea, Brazil, Ethiopia, and Colombia-decaffeine), rational combination of TFT transfer and dynamic response curves capture the liquids and gases-dependent electrical transport behavior and principal component analysis (PCA)-assisted machine learning (ML) is implemented. A PCA-assisted ML model distinguished the four target flavors with >92% prediction accuracy. ML-based regression model predicts the flavor chemical concentrations with >99% accuracy. Also, the classification model successfully distinguished four different types of coffee-bean with 100% accuracy.

Hyaluronic acid applied as a natural flavor enhancer and its mechanism exploration

Creating natural flavor enhancers presents a promising approach to reducing excessive seasoning consumption. This study aimed to determine whether food-grade hyaluronic acid could serve as a viable option to decrease salt content in low-sodium foods without sacrificing saltiness. Using both an artificial tongue and quartz crystal microbalance with dissipation (QCM-D), we examined the effects of different molecular weights (100 kDa, 400 kDa) and concentrations (0.2% w/v, 0.4% w/v) of hyaluronic acid (HA) on the saltiness perception of NaCl solutions. HA has been confirmed with a taste-enhancing effect. Furthermore, when added to pre-made dishes such as Sichuan fish and black pepper steak, HA was found to maintain the saltiness of the sample with at least 10% less salt added. Simulation with a hydrogel artificial tongue revealed that Na+ adhesion positively correlated with increasing molecular weight and concentration of HA. The QCM-D results supported this finding, showing that 100 kDa HA enabled greater permeation of Na+ into the oral mucosal layer and thus showed a stronger perception of saltiness in comparison to 400 kDa HA. Overall, the mucoadhesion and mucopenetration of HA make it a promising alternative to traditional seasonings and could facilitate the pursuit of healthier dietary habits.

The Science of Melting Chocolate: An artificial tongue illuminates how chocolate changes from solid to smooth emulsion.

The Science of Melting Chocolate: An artificial tongue illuminates how chocolate changes from solid to smooth emulsion.

Bioinspired multi-stimulus responsive MXene-based soft actuator with self-sensing function and various biomimetic locomotion

Although a series of outstanding achievements have been realized so far, developing soft actuators that can respond to various stimuli and simulate biological versatility (e.g., self-sensing function, diverse locomotion, etc.) is still a great challenge. Here, by utilizing internal stress generated spontaneously during the preparation process, an originally rolled MXene/polydimethylsiloxane (PDMS) bimorph soft actuator has been designed and fabricated. Based on the outstanding photothermal/electrothermal conversion efficiency and adjustable interlayer d-spacing change of Ti3C2Tx MXene, and the large thermal/chemical vapor expansion of crosslinked PDMS, this actuator can produce reversible large deformation under various forms of stimulus, including heat, light, electric, and n-hexane vapor. More importantly, microcracks can be formed spontaneously on the surface of MXene layer during the fabrication process of the actuator, which causes the resistance of MXene layer to be very sensitive to mechanical deformation. Based on this, a light-driven artificial tongue is fabricated, which not only mimic the ejection motion and catching prey behavior of the frog’s tongue, but also perceive the touching object. Moreover, a series of sophisticated biomimetic locomotion such as jumping, crawling, and self-oscillation all can be realized by using this soft actuator. Besides, the actuator with rolled initial structure can also be an intelligent gripper with low energy consumption. By doping Fe3O4 nanoparticles in PDMS matrix, the composite actuator can carry object to through complex maze in adjustable magnetic field without additional stimulation. This MXene-based actuator provides new insights in design of next generation of smart actuators with multi-functions and multiform motions.

CaMKII-Dependent Contractile Dysfunction and Pro-Arrhythmic Activity in a Mouse Model of Obstructive Sleep Apnea.

Left ventricular contractile dysfunction and arrhythmias frequently occur in patients with sleep-disordered breathing (SDB). The CaMKII-dependent dysregulation of cellular Ca homeostasis has recently been described in SDB patients, but these studies only partly explain the mechanism and are limited by the patients' heterogeneity. Here, we analyzed contractile function and Ca homeostasis in a mouse model of obstructive sleep apnea (OSA) that is not limited by confounding comorbidities. OSA was induced by artificial tongue enlargement with polytetrafluorethylene (PTFE) injection into the tongue of wildtype mice and mice with a genetic ablation of the oxidative activation sites of CaMKII (MMVV knock-in). After eight weeks, cardiac function was assessed with echocardiography. Reactive oxygen species (ROS) and Ca transients were measured using confocal and epifluorescence microscopy, respectively. Wildtype PTFE mice exhibited an impaired ejection fraction, while MMVV PTFE mice were fully protected. As expected, isolated cardiomyocytes from PTFE mice showed increased ROS production. We further observed decreased levels of steady-state Ca transients, decreased levels of caffeine-induced Ca transients, and increased pro-arrhythmic activity (defined as deviations from the diastolic Ca baseline) only in wildtype but not in MMVV PTFE mice. In summary, in the absence of any comorbidities, OSA was associated with contractile dysfunction and pro-arrhythmic activity and the inhibition of the oxidative activation of CaMKII conveyed cardioprotection, which may have therapeutic implications.

Artificial tongue based on carbon dots and a porphyrin derivative for pattern recognition of metal ions

An array-based artificial tongue consisting of C-dots, TMPyP (porphyrin derivative) and a C-dot–TMPyP complex for the discrimination of different metal ions.

Machine-learning assisted multiplex detection of catecholamine neurotransmitters with a colorimetric sensor array.

Catecholamine neurotransmitters (CNs), such as dopamine (DA), epinephrine (EP), norepinephrine (NEP), and levodopa (LD), are recognized as the primary biomarkers of a variety of neurological illnesses. Therefore, simultaneous monitoring of these biomarkers is highly recommended for clinical diagnosis and treatment. In this study, a high-performance colorimetric artificial tongue has been proposed for the multiplex detection of CNs. Different aggregation behaviors of gold nanoparticles in the presence of CNs under various buffering conditions generate unique fingerprint response patterns. Under various buffering conditions, the distinct acidity constants of CNs, and consequently their predominant species at a given pH, drive the aggregation of gold nanoparticles (AuNPs). The utilization of machine learning algorithms in this design enables classification and quantification of CNs in various samples. The response profile of the array was analyzed using the linear discriminant analysis algorithm for classification of CNs. This colorimetric sensor array is capable of accurately distinguishing between individual neurotransmitters and their combinations. Partial least squares regression was also applied for quantitation purposes. The obtained analytical figures of merit (FOMs) and linear ranges of 0.6-9 μM (R2 = 0.99) for DA, 0.1-10 μM (R2 = 0.99) for EP, 0.1-9 μM (R2 = 0.99) for NEP and 1-70 μM (R2 = 0.99) for LD demonstrated the potential applicability of the developed sensor array in precise and accurate determination of CNs. Finally, the feasibility of the array was validated in human urine samples as a complex biological fluid with LODs of 0.3, 0.5, 0.2, and 1.9 μM for DA, EP, NEP, and LD, respectively.

A pH-Sensitive, Stretchable, Antibacterial Artificial Tongue Based on MXene Cross-Linked Ionogel.

Dehydration has always been a confusing problem for a hydrogel exposed to air, which restricts its application in practical detection. While an ionogel with unique properties can lock water molecules efficiently due to its low vapor pressure, the design and development of an ionogel with excellent water-locking properties and stability to achieve satisfactory detection are thus highly desirable. In this work, a pH-sensitive, stretchable, antibacterial, and stable ionogel artificial tongue was fabricated through dual cross-linking. The artificial tongue consisted of MXene as a cross-linking agent, phenol red as an indicator, gelatin, N-(2-hydroxyethyl) acrylamide, and 1-butyl-3-methylimidazolium chloride as the three-dimensional polymer network. A small quantity of MXene was used as a cross-linker the first time to promote the initiator in the system to generate free radicals, accelerating the reaction process and the multilevel linkage among the polymers. Meanwhile, the indicator phenol red was introduced into the ionogel successfully for the first time, showing great stability in 5 weeks. After evaluation by the Brand-Altman analysis, it was found that the method of pH measurement using ionogels had good consistency with the pH meter measurement method. Additionally, the prepared ionogel presented excellent water retention, mechanical stretchability, antibacterial property, and stability, as well as good test results in the test of artificial simulated saliva, demonstrating great potential in clinical applications.

Artificial Tongue Embedded with Conceptual Receptor for Rubber Gustatory Sensor by Electrolytic Polymerization Technique with Utilizing Hybrid Fluid (HF)

The development of gustatory sensors is essential for the development of smart materials for use in robotics, and in the food, beverage, and pharmaceutical industries. We therefore designed a prototype of a rubber tongue embedded with a gustatory receptor mimicking a human tongue using our previously proposed hybrid fluid rubber (HF rubber) and an electrolytic polymerization technique. The fabricated gustatory receptor was composed of Pacinian corpuscles, which are well known and have already been elucidated as effective haptic and auditory receptors in previous studies. Moreover, the receptor has self-powered voltage generated as built-in electricity as a result of the ionized particles and molecules in the HF rubber. The utilization of a layered structure for the Pacinian corpuscles induced a typical response not only to normal and shear forces but to thermal variations. Typical gustatory characteristics, including the initial response voltage and the cyclic voltammogram form, were clearly varied by five tastes: saltiness, sourness, sweetness, bitterness, and umami. These results were due to ORP, pH, and conductivity.

Ultralow‐Power and Multisensory Artificial Synapse Based on Electrolyte‐Gated Vertical Organic Transistors

AbstractBioinspired electronics have shown great potential in the field of artificial intelligence and brain‐like science. Low energy consumption and multifunction are key factors for its application. Here, multisensory artificial synapse and neural networks based on electrolyte‐gated vertical organic field‐effect transistors (VOFETs) are first developed. The channel length of the organic transistor is scaled down to 30 nm through cross‐linking strategy. Owing to the short channel length and extremely large capacitance of the electric double layer formed at the electrolyte–channel interface, the minimum power consumption of one synaptic event is 0.06 fJ, which is significantly lower than that required by biological synapses (1–10 fJ). Moreover, the artificial synapse can be trained to learn and memory images in a 5 × 5 synapse array and emulate the human brain's spatiotemporal information processing and sound azimuth detection. Finally, the artificial tongue is designed using the synaptic transistor that can discriminate acidity. Overall, this study provides new insights into realizing energy‐efficient artificial synapses and mimicking biological sensory systems.

Newly designed flat surface artificial tongue system for speech improvement in glossectomy patients: A preliminary study.

To design an efficient tongue prosthesis with reproducibility and to objectively evaluate improvement in speech function. A silicon anatomical artificial tongue (AT) and a flat surface artificial tongue system (FTS) were used in our study. Twenty healthy participants (10 males and 10 females, 26.3 ± 1.8 years) were fitted with a tongue movement suppression appliance (TSA) that fit the dental arch to simulate the glossectomy condition. TSA, TSA + FTS, and TSA + AT simulated the state of glossectomy patients without artificial tongue, with normal artificial tongue, and newly designed artificial tongue, respectively. Three speech intelligibility tests were performed for each of the following conditions: pronouncing 100 Japanese monosyllables, 40 Japanese words, and reading a short story. One-way ANOVA, Wilcoxon signed-rank test, and Tukey-Kramer post-hoc test were used for statistical analyses. Significant differences were observed for 100 Japanese monosyllables and 40 Japanese words between the TSA + FTS, TSA, and TSA + AT conditions (p < 0.05). Regarding the speech intelligibility test for reading a short story, the TSA + FTS condition resulted in a significantly higher speech intelligibility than the TSA and TSA + AT conditions (p < 0.05). A flat surface artificial tongue system contributed to the improvement in speech function. This structure can be easily used in cases where conventional artificial tongue are applicable, regardless of variation in the oral condition; thus, making it a widely applicable treatment option for glossectomy patients.

Design of an Artificial Tongue Driven by Shape Memory Alloy Fibers.

Dysphasia is one of the complications which may cause functional disability after the surgical treatment of oral cancer. The loss of the function derived by tongue and other oral tissues impairs the retention and delivery of liquids and food masses as well as the swallowing motion into pharynx. As accumulation of liquids or food masses in the larynx can lead to pneumonia, therefore swallowing support to improve each coordination of the tongue, the epiglottis and the esophagus in the process of swallowing is highly desirable. In this study, we designed a new artificial tongue which was capable of contracting to deliver the bolus masses in the swallowing propulsion phase in the oral cavity. We designed a two-layered artificial tongue simulating the anatomical identical muscle structures with the longitudinal muscle, and the transverse muscle-genioglossus layer. A silicone rubber material was used for the surface layer, and the covalent shape memory alloy fibers (diameter: 150µm) were implemented in the secondary structure beneath of the silicone rubber material of the artificial tongue. Its contraction was driven by with shape memory alloy fibers shortage inside of the artificial tongue unit. The actuation was accurately controlled by the originally designed electrical current input with pulse width modulation. Firstly, we examined a prototype structure of the artificial tongue as well as the changes in unit thickness as it constricted by electric power supply switching. Secondly, we performed a feasibility study of the prototype into the head-neck medical training model with larynx-tracheal structure with esophagus. The results were as follows: a) the artificial tongue model showed a large contraction with a motion to increase upward pressure, b) the tongue unit expressed the capability of reducing shallow space between dorsal tongue surface and palate in the oral cavity model. Therefore, the first artificial tongue design with active contractile motion will be useful orally installable device for improving delivery function of bolus masses through swallowing procedure in dysphasia.Clinical Relevance- The active artificial tongue system designed for the first time exhibited an effective contractile motion to support bolus food masses propulsion in swallowing process in the oral cavity in the patients with dysphasia.

Orodispersible Membranes from a Modified Coaxial Electrospinning for Fast Dissolution of Diclofenac Sodium.

The dissolution of poorly water-soluble drugs has been a longstanding and important issue in pharmaceutics during the past several decades. Nanotechnologies and their products have been broadly investigated for providing novel strategies for resolving this problem. In the present study, a new orodispersible membrane (OM) comprising electrospun nanofibers is developed for the fast dissolution of diclofenac sodium (DS). A modified coaxial electrospinning was implemented for the preparation of membranes, during which an unspinnable solution of sucralose was explored as the sheath working fluid for smoothing the working processes and also adjusting the taste of membranes. SEM and TEM images demonstrated that the OMs were composed of linear nanofibers with core-sheath inner structures. XRD and ATR-FTIR results suggested that DS presented in the OMs in an amorphous state due to the fine compatibility between DS and PVP. In vitro dissolution measurements and simulated artificial tongue experiments verified that the OMs were able to release the loaded DS in a pulsatile manner. The present protocols pave the way for the fast dissolution and fast action of a series of poorly water-soluble active ingredients that are suitable for oral administration.

Comprehensive CircRNA Profiling and Selection of Key CircRNAs Reveal the Potential Regulatory Roles of CircRNAs throughout Ovarian Development and Maturation in Cynoglossus semilaevis.

Simple SummaryCircRNAs: as molecules involved in gene regulation, have become a new research hotspot in the non-coding RNA field. CircRNAs show tissue- or developmental stage-specific patterns of expression and can influence the expression levels of their parental genes. Recent studies have documented the potential biological roles of circRNAs in the growth, development, reproduction and health of humans and animals. Tongue sole (Cynoglossus semilaevis) is a marine flatfish that is an economically important farmed species in China. The commercial aquaculture of tongue sole has developed in the last few years because wild resources have decreased. Reproduction is regulated by brain-pituitary-gonad-liver axis which limits the development of artificial tongue sole culture. However, the roles of circRNAs in the ovarian development and maturation of tongue sole has never been reported. The identification of the potential functions of circRNAs provides a foundation for understanding the genetic mechanisms that regulate oocyte growth and maturation, which will allow the efficiency of tongue sole reproduction to be improved. Moreover, our findings extend the knowledge about a new type of endogenous RNA involved in regulating the ovarian development and maturation of tongue sole.CircRNAs are novel endogenous non-coding small RNAs involved in the regulation of multiple biological processes. However, little is known regarding circRNAs in ovarian development and maturation of fish. Our study, for the first time, provides the genome-wide overview of the types and relative abundances of circRNAs in tongue sole tissues during three ovarian developmental stages. We detected 6790 circRNAs in the brain, 5712 in the pituitary gland, 4937 in the ovary and 4160 in the liver. Some circRNAs exhibit tissue-specific expression, and qRT-PCR largely confirmed 6 differentially expressed (DE) circRNAs. Gene Ontology and KEGG pathway analyses of DE mRNAs were performed. Some DE circRNA parental genes were closely associated with biological processes in key signalling pathways and may play essential roles in ovarian development and maturation. We found that the selected circRNAs were involved in 10 pathways. RNase R digestion experiment and Sanger sequencing verified that the circRNA had a ring structure and was RNase R resistant. qRT-PCR results largely confirmed differential circRNA expression patterns from the RNA-seq data. These findings indicate that circRNAs are widespread in terms of present in production-related tissues of tongue sole with potentially important regulatory roles in ovarian development and maturation.

Ultrasound monitoring of a deformable tongue-food gel system during uniaxial compression–an in vitro study

This study presents a novel ultrasound method for exploring the mechanical deformability of artificial tongue models (ATMs) topped with agar and/or gelatin food gels during uniaxial compression. The ATMs were made from polyvinyl alcohol and displayed different levels of rigidity and surface roughness. We quantified deformation of the ATM-food system as it underwent compression induced by a texture analyzer. We collected real-time measurements via an ultrasound transducer (1 MHz) placed beneath the ATM, enabling to monitor non-invasively the ultrasound time of flight (ToF) and the apparent reflection coefficient (R*) of the ATM-food interface. The results on ToF reflected the tie between the level of force and ATM deformation; they were also precise enough to identify gel fracture. R* was a crucial parameter influenced by both ATM properties (rigidity, surface roughness) and food gel properties (syneresis, ability to mold to surface asperities).

Texture contrast: Ultrasonic characterization of stacked gels’ deformation during compression on a biomimicking tongue

When undergoing compression during oral processing, stacked gels display different mechanical properties that shape perceptions of texture contrasts (Santagiuliana et al., 2018). However, to date, characterizing the mechanical responses of individual gel layers has been impossible. In this study, an ultrasound (US) technique was developed, that allowed such deformation dynamics to be visualized in real time. Stacked gels were created using layers (height: 5 mm) of brittle agar and elastic gelatin in different combinations. In a series of experimental tests, different stacked gel combinations were placed on a rough, deformable artificial tongue model (ATM) made of polyvinyl alcohol; a texture analyzer was used to apply uniaxial force, and deformation was monitored by an US transducer (5 MHz) located under the ATM.From the obtained results, it was observed that the deformation of ATM surface during compression was in accordance with the force recorded by the texture analyzer, suggesting a collaborative response of different layers under compression. Moreover, US imaging revealed that differences in Young's modulus values between layers led to heterogeneous strain distributions, which were more pronounced for the agar layers. Biopolymer elasticity was also a key factor. Regardless of combination type, the gelatin layers never fractured; such was not the case for the agar layers, especially those with lower Young's modulus values. The results of this US study have thus paved the way for a better understanding of the mechanical deformation that occurs in heterogeneous foods, a phenomenon that has been difficult to examine because of the limitations of conventional techniques.

3D Biomimetic Tongue-Emulating Surfaces for Tribological Applications.

Oral friction on the tongue surface plays a pivotal role in mechanics of food transport, speech, sensing, and hedonic responses. The highly specialized biophysical features of the human tongue such as micropapillae-dense topology, optimum wettability, and deformability present architectural challenges in designing artificial tongue surfaces, and the absence of such a biomimetic surface impedes the fundamental understanding of tongue–food/fluid interaction. Herein, we fabricate for the first time, a 3D soft biomimetic surface that replicates the topography and wettability of a real human tongue. The 3D-printed fabrication contains a Poisson point process-based (random) papillae distribution and is employed to micromold soft silicone surfaces with wettability modifications. We demonstrate the unprecedented capability of these surfaces to replicate the theoretically defined and simulated collision probability of papillae and to closely resemble the tribological performances of human tongue masks. These de novo biomimetic surfaces pave the way for accurate quantification of mechanical interactions in the soft oral mucosa.

Testing of fast dissolution of ibuprofen from its electrospun hydrophilic polymer nanocomposites

The dissolution of poorly water-soluble drug poses a big challenge to the researchers in drug discovery. Electrospun nanofibers have been broadly demonstrated as good candidates for resolving this issue. However, the testing methods are often indiscriminate with the drug sustained release profiles. In this study, a new coaxial solid core spinneret was developed to carry out the preparation of ibuprofen (IBU)-loaded polyvinylpyrrolidone (PVP) nanofibers. These nanofibers have an average diameter of 740 ± 130 nm with linear morphology, smooth surface and smooth cross-section without any solid phase separation, as verified by SEM images. XRD and DSC results suggested that IBU presented in the fibers in an amorphous state thanks to their fine compatibility, as disclosed by FTIR spectra. Four different methods (a polarized microscope, an artificial tongue, a contact angle meter, and the in vitro dissolution tests) are exploited to assess the fast dissolution properties of the fibers. Their results concurred the fine functional performances of electrospun nanofibers on improving the dissolution rate of IBU from different standpoints, with 100.3 ± 4.2% of the loaded IBU freed into the dissolution media within the first minute. They are synergistic effects of hydrophilic polymer, large surface and porosity of electrospun nanofiber mats, and amorphous state of the drug.

Supramolecular Sensor for Astringent Procyanidin C1: Fluorescent Artificial Tongue for Wine Components.

An artificial tongue that detects astringent components for a comprehensive evaluation of taste has not been established to date. Herein, we first propose fluorescent polythiophene (PT) derivatives (S1-S3) modified with 3-pyridinium boronic acid as supramolecular chemosensors for wine components including astringent procyanidin C1. After numerous attempts for the synthetic conditions, more than 95 mol % of the PT unit was modified with the pyridinium boronic acid moiety. To evaluate the PT derivatives as chemosensors of the artificial tongue, qualitative and quantitative analyses were performed with four types of wine components (i.e., sweet, sour, bitter, and astringent tastes) in combination with pattern recognition models. Notably, procyanidin C1 in the actual wine sample was successfully detected in a quantitative manner. In other words, we have established an authentic artificial tongue using PT based supramolecular chemosensors.