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All-in-one terahertz taste sensor: integrated
electronic and bioelectronic tongues
Jin Wang,* Kenji Sakai and Toshihiko Kiwa

Taste sensors, also known as electronic tongues or bioelectronic tongues, are designed to evaluate foodand beverages, as well as for medical diagnostics. These devices mimic the ability of the human tongue todetect and identify different tastes in liquid samples, such as sweet, sour, salty, bitter, and umami. In thisstudy, a novel all-in-one terahertz taste sensor was proposed, which differs from traditional
electrochemical approaches. This sensor utilizes terahertz technology for imaging and sensing chemical
reactions on the terahertz semiconductor emitter surface. The surface can be functionalized with ionsensitive membranes, proteins, DNA aptamers, and organic receptors, enabling the detection of various
substances, such as solution pH, physiological ions, sugars, toxic chemicals, drugs, and explosives.
Received 10th February 2023,
Accepted 11th March 2023
DOI: 10.1039/d3sd00038a

Terahertz taste sensors offer several advantages, including being label-free, high sensitivity and selectivity,
rapid response, minimal sample consumption, and the ability to detect non-charged chemical substances.
By integrating multiple receptors or sensing materials on a single chip, the all-in-one terahertz taste sensor
has significant potential for future taste substance detection, nutrition evaluation, metabolite and drug

rsc.li/sensors

monitoring, and biomarker sensing.

Taste sensors
Taster sensors, also known as electronic or bioelectronic
tongues, are devices that mimic the human sense of taste byidentifying and measuring different chemical compounds ina sample solution. Researchers began developing taste
sensors in the late twentieth century to analyze the chemicalcompounds found in foods and beverages, which are difficult
to measure or identify. These electronic tongues are generally
potentiometric or amperometric devices or equipment with
ion-selective electrodes,1 metal oxides,2,3 or artificial lipid
polymer arrays,4–8 which can detect or measure changes in
pH and ion concentration as well as identify a wide range oftaste substances or chemical compounds in liquid samples(milk, beer, tea, etc.) by measuring the electrical potential or
current. Legin et al. developed a sensor array-based electronic
tongue and pattern recognition algorithm for the qualitative
measurement of several different beverages.9 Dias et al.
successfully built 36 cross-sensibility sensors for therecognition of five basic taste substances.10 Moreover, several
sensor devices and equipment have been manufactured andcommercialized for laboratory research and industrial
applications. For example, the TS-5000Z taste sensing system

Graduate School of Interdisciplinary Science and Engineering in Health Systems,
Okayama University, 3-1-1, Tsushima-Naka, Kitaku, Okayama, 700-8530, Japan.
E-mail: wangjin@okayama-u.ac.jp

620 | Sens. Diagn., 2023, 2, 620–626(Fig. 1A), developed by Professor Toko and Intelligent Sensor
Technology Inc., Japan, detects five basic tastes, flavor
properties (sharpness and richness), and taste masking
properties (Fig. 1B).11,12 Another commercial tongue consistsof seven ion-selective field effect transistors (ISFET) developedby Astree II (Alpha MOS, Toulouse, France), which are also
featured in taste evaluation, food quality control, andpharmaceutical industry applications.
In the early twenty-first century, another importantdevelopment of the bioelectronic tongue was presented toanalyze complex mixtures of chemical compounds and identify
individual compounds that are not available using traditional
methods.13–16 Bioelectronic tongues are based on a variety ofrecognition elements,17–23 such as nucleic acids, proteins,antibodies, cells, and taste receptors. A key feature ofbioelectronic tongues is their high selectivity and sensitivity.
This enables the identification of specific chemical compounds
that may not be detectable using traditional analytical methods.
Furthermore, bioelectronic tongues can be used for thedetection of biomolecules, such as proteins and nucleic acids,
using enzyme-, antibody-, or nucleic acid-based receptors. Qin
et al. proposed a biohybrid tongue that combines a
microelectrode array chip with mammalian gustatory
epithelium to create a highly sensitive taste sensing system. The
study quantified the interaction effects of sourness on
sweetness, revealing that suppression of sweetness by sourness
increases with the concentration of the sour stimulus (Fig. 2).
Jeong et al. successfully developed an ultrasensitive artificial© 2023 The Author(s). Published by the Royal Society of ChemistryView Article Online

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Fig. 1 (A) Taste sensor (TS-5000Z) system, configuration, and lipid/polymer membrane. (B) TS-5000Z sensor response versus five basic tastes andastringency substances. Reprinted with permission from ref. 12, copyright 2023, Elsevier.

sweet taste bioelectronic tongue based on the T1R2 VFT of ahuman sweet taste receptor, which detects substances down toa limit of 0.1 fM and selectively discriminates sweet substancesfrom other taste substances (Fig. 3).
Recent advancements in technology, materials science,computational biology, and artificial intelligence have enabled
the incorporation of novel receptors and material structures
into taste sensors. These include metallic nanostructure-based
plasmonic sensors,24,25 voltammetric electronic tongue withmachinelearning
algorithms,26
andelectrochemical
27,28
sensors.
These advancements have significantly enhanced
the performance of electronic and bioelectronic tongues,
thereby offering more accurate and robust measurements.

Current challenges
Taste sensors are still considered a research area and are notwidely employed in commercial applications. They have beenused in laboratory settings to analyze a wide range ofsamples, including foods and beverages and medical andFig. 2 Biohybrid tongue. (A) Human gustatory system. (B) Gustatory
epithelium functionalized microelectrode array chip. Reprinted withpermission from ref. 19, copyright 2022, American Chemical Society.

© 2023 The Author(s). Published by the Royal Society of Chemistry

environmental samples. They have also been used for quality
control in the food and beverage industry, as well as inmedical diagnostics.
However, they have difficulties in detecting and selectively
identifying non-charged taste substances such as glucose andcaffeine, lack applicability for detecting nutrients, drugs,
metabolites, and heavy ions at the same time, and have
limitations in the design of bioreceptors for multiplex
sensing.
There is still a need for further development andvalidation to make them more practical for commercial use.
Scientists are still working on developing and improving
electronic and bioelectronic tongues with the goal of making
them more accurate, reliable, and practical for commercial
use. This includes developing new sensors, improving signal
processing and data analysis methods, and reducing thecosts of the devices. The main challenges in the development
and practical use of electronic and bioelectronic tongues
include the following:• Require more receptors or sensing materials for multianalyte measurement.

Fig. 3 Bioelectronic tongues. (A) Sweet taste receptor-based CNT-FET
tongue. (B) Real-time sensor response corresponding to different
concentrations of sucrose solutions. Reprinted with permission fromref. 23, copyright 2022, American Chemical Society.

Sens. Diagn., 2023, 2, 620–626 | 621

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Table 1 Main chemical compounds and properties of the five basic tastes

Taste

Chemical compounds

Properties

Sweet
Sour
Salty
BitterUmami

Glucose, fructose, sucrose
Citric acid, lactic acid, acetic acid
Sodium, potassium, other minerals
Caffeine, quinine, alkaloids
Amino acids, glutamate, aspartate

Source of natural sugar and vitamins
Source of vitamin C
Maintain electrolyte balance
Noxious compounds but some have beneficial effects
Provide essential amino acids and other nutrients• Improve the accuracy and reliability with machinelearning algorithms and data analysis approaches.
• Reduce the cost of the sensor system or device
equipment for commercialization.
• Simplify the sample preparation process and operationof the sensor system.
• Integrate multiple sensors or obtain a more precise andcomprehensive view.
• Conduct standardization when using the taste sensors.
Sensing materials and receptors play a critical role in thedevelopment of advanced taste sensors. In recent years, there
have been several widely used sensing materials or receptors forsensing taste chemical compounds in electronic andbioelectronic tongues. These include ion-selective membranes,
metal oxides, artificial lipid polymer membranes, andbioreceptors, including enzymes, antibodies, nucleic acids, andcells. For example, cell-based bioelectronic tongues can behighly selective but are also more expensive to produce andmaintain, require more time to prepare, and have limited
selectivity and specificity in detecting certain chemicalcompounds compared to other types of sensors.
As is well-known, thousands of chemical compounds
contribute to taste, including sweet, sour, salty, bitter, andumami tastes. Table 1 shows a summary of the main substancesand properties of the five basic tastes. Specific compounds that
contribute to each taste can vary depending on the food orbeverage being tasted. Measuring certain taste substances, suchas noncharged glucose and caffeine, using potentiometricelectronic tongues can be challenging. Therefore, further researchis needed to develop new taste receptors or sensing materials
coupled with nanotechnology and microfabrication techniques
for advanced taste sensor development. For example, conductive
polymers, organic and inorganic materials, nanomaterials, andartificial receptor molecularly imprinted polymers (MIP) havebeen widely developed for electronic tongue development.29–31
These sensing materials can be integrated into electronic devices
such as field-effect transistors (FET), quartz crystal microbalances(QCM), surface plasmon resonance sensors (SPR), or cantileversensors through an array-based approach and machine learningalgorithms to detect and identify the target chemical compoundswith high-throughput, simple, and low-cost measurements,
overcoming the current challenges.32 Additionally, nanomaterials
such as carbon nanotubes can be combined with bioreceptors,
enzymes, antibodies, cells, or other biological molecules todevelop more sensitive and specific taste sensors.
For bioelectronic tongue development, small receptors like
peptides or aptamers over antibodies, cells, or enzymes have622 | Sens. Diagn., 2023, 2, 620–626

several advantages such as the following: they can beengineered to have specific binding properties and areversatile and easier to synthesize with low cost, which makes
them ideal for use in biosensors and diagnostic assays. To
better understand taste receptors for taste substanceperception, in silico investigation is required. AlphaFold2 is a
novel computational method that utilizes deep learning andneural networks to predict the structures of proteins fromthe amino acid sequences.33–35 It is a valuable tool for
researchers in the fields of structural biology andbioinformatics because it eliminates the need for costly andtime-consuming experimental methods to determine theprotein structure. As shown in Fig. 4A and B, a new bitter
taste receptor, TAS2R20, which is a G protein-coupled
receptor (GPCR), was predicted and analyzed by moleculardocking.36 Three typical bitter chemicals – quinine,
humulone, and caffeine – interact with TAS2R20 withdifferent binding affinities, and the binding residues areshown in Fig. 4C. This indicates how bitter moleculesinteract with taste proteins. Additionally, the binding motif
was predicted, which can aid in the future design of short
peptides for binding bitter substances using artificial neuralnetworks (Fig. 4D and E).
Many studies have used computational algorithms to predict
the structure and binding properties of peptides, including

Fig. 4 AlphaFold2 prediction of Homo sapiens TAS2R20 (taste
receptor type 2 member 20) computational molecular docking
simulation and design for bitter compound perception. (A) Typical
bitter compounds. (B) TAS2R20 structure and molecular docking with
bitter compounds. (C) Binding properties of a receptor–ligand
complex. (D) Predicted binding motif via multiple Em for motif
elicitation. (E) Molecular docking of a binding motif–ligand complex.

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computational design of odorant-binding peptides or rational
design of binding peptides from odorant-binding proteins(OBPs),37–40 which can be a very efficient way to identify
potential candidates for further experimentation. In ourprevious study, we rationally designed a small receptor peptide
from an anti-TNT monoclonal antibody in the complementarity
determination region (CDR) (Fig. 5A and B), which is theantigen-binding region. Based on the molecular docking
simulation and array-based fluorescence measurements(Fig. 5C), 15-mer amino acid peptides were selected as the TNTbinding peptides.41,42 The small receptor exhibited high affinity(Kd = 10.14 nM) for targeting TNT molecules and excellent
selectivity.43 These studies revealed a novel approach for thedevelopment of small receptors.

All-in-one terahertz taste sensor
Terahertz (THz) waves are electromagnetic radiation that fall
between the microwave and infrared frequencies in the

Perspective
electromagnetic spectrum. They have a frequency range ofapproximately 0.1 to 10 THz. THz waves have uniqueproperties that make them useful for a variety of applications
in different fields, such as spectroscopy, imaging, sensing,communications, materials science, etc.44 Terahertz
technology has been considered as a potential method fortaste sensing, environmental monitoring, and medical
diagnosis, as it offers a non-invasive, highly sensitive,
selective, and label-free method for detecting chemicalcompounds and identifying their concentrations in a sample.
Our group developed an advanced terahertz chemical
microscope (TCM). The TCM utilizes a semiconductor device,
known as the sensing plate, to visualize the electrical potential
distribution.45–49 The sensing plate was constructed bydepositing a thin silicon film on a sapphire substrate and thenadding a silicon oxide layer on the top (Fig. 6A). The thicknessof the silicon film was 500 nm and that of the silicon oxide film
was several nanometers (Fig. 6B and C). The sensing plate was
10 mm square for easy handling; however, it can be fabricatedto wafer size depending on the sensing area that needs to bemeasured. The defects near the boundary between the siliconand silicon oxide films caused the energy band to bend towards
the boundary surface, creating a depletion layer electric field.
The direction of the bend depended on the doping type of thesilicon film. When a femtosecond laser pulse with photon
energy equal to or greater than the silicon bandgap was applied
to the sensor plate from the substrate side, the charge carriers
within the silicon film were excited and accelerated by thedepletion layer electric field. As shown in eqn (1), the amplitude
intensity of the generated terahertz wave (ETHz) is proportionalpﬃﬃﬃ
to the square root of the electric potential ( ϕ ). In thisequation, El represents the depletion layer, e represents theelectric elementary charge, N represents the electric charge
density per unit area, and ε0 denotes the dielectric constant ofvacuum. Therefore, various types of chemical reactions
occurring on the sensing plate can be measured.
ETHz ðtÞ ∝ El ¼

Fig. 5 Rational design of a TNT binding peptide from an anti-TNT
monoclonal antibody. (A) Structure of the TNT antibody, CDR anddesigned binding peptide. Reprinted with permission from ref. 42,
copyright 2018, Elsevier. (B) Homology modelling and amino acidsequence analysis. (C) Experimental fluorescence results of the arraybased peptide measurements (left), docking simulation (middle), andsurface plasmon resonance kinetic analysis (right). Reprinted withpermission from ref. 41 and 43, copyright 2017, American Chemical
Society. Copyright 2019, Elsevier.

© 2023 The Author(s). Published by the Royal Society of Chemistrypﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃ pﬃﬃﬃ
ð2eN=ε0 Þ × ϕ(1)Fig. 6 (A) Schematic of the energy band of the terahertz sensing
plate. (B) Components of the terahertz sensing plate. (C) A photographof the plastic holder for microwell formation and the sensing plate.
Reprinted with permission from ref. 53, copyright 2023, Elsevier.

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Perspective
To address the challenges, an innovative solution – an allin-one terahertz taste sensor – has been proposed. Thisterahertz taste sensor can detect and quantify a diverse rangeof chemicals and biochemicals using multi-well arrays on asingle semiconductor chip (sensing plate). It can visualize
chemical and biochemical reactions with minimal sample
volume consumption by using a terahertz chemical

Sensors & Diagnostics
microscope system. This technology has shown a wide rangeof potential applications (Fig. 7A and B), including measuringphysiological ions, the solution pH, non-charged molecules(Fig. 7C and D), sugars (Fig. 7E), toxic chemicals and drugs(Fig. 7F), enzyme kinetics, detecting cancer cells, analyzing
the binding of antibodies and antigens in immunoassays,
and evaluating cosmetic products and lithium-ion

Fig. 7 (A) Multifunctional terahertz chemical microscope in a variety of applications. Reprinted with permission from ref. 54. Copyright 2022 MDPI
(Basel, Switzerland). (B) Sensing plate functionalization methods. Reprinted with permission from ref. 54. Copyright 2021 MDPI (Basel, Switzerland).
(C) Visualization of pH, Na+, K+, and Ca2+. Reprinted with permission from ref. 45 and 54. Copyright 2018 Optical Society of America and SPIE.
Reprinted with permission from ref. 53. Copyright 2023, Elsevier. (D) DNA aptamer-based terahertz chip for non-charge cortisol detection withhigh sensitivity. Reprinted with permission from ref. 53, copyright 2023, Elsevier. (E) Sensitive detection of the sugar compound mannose.
Reprinted with permission from ref. 45. Copyright 2019 MDPI (Basel, Switzerland). (F) TNT explosive (left) and toxic histamine detection (right).
Reprinted with permission from ref. 53. Copyright 2023, Elsevier and reprinted with permission from ref. 55. Copyright 2022 MDPI (Basel,
Switzerland).

624 | Sens. Diagn., 2023, 2, 620–626© 2023 The Author(s). Published by the Royal Society of ChemistryView Article Online

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batteries.50–54 The terahertz sensing plate can befunctionalized with ion-sensitive membranes, DNA aptamers,organic molecules, proteins, and antibodies.53,55 By
measuring and visualizing the distribution of theelectrochemical potential on the semiconductor sensing
plate, the TCM can provide detailed information aboutchemical reactions. Furthermore, the TCM is a label-free,highly sensitive technology that can detect chemical andphysical changes in the terahertz sensing plate. Unlike otherestablished techniques such as FETs, SPR, QCMs, lightaddressable
potentiometricsensors(LAPS),
andelectrochemical sensors, the TCM does not have thelimitations of Debye length design, molecular mass weightand charged molecule requirements or three electrodes
requirements.56–59 For example, non-charged toxic and drug
compounds have been successfully measured by simply
modifying the semiconductor chip with a polymer and a DNA
aptamer based on charge-transfer complex formation andconformational changes of the negatively charged DNA
structure.53 Moreover, as previously discussed, thedevelopment of a wide range of bioreceptors and sensing
materials through in silico or rational design, combined withthe all-in-one terahertz taste sensor, could accelerate thedevelopment of multi-receptor arrays for detecting various
types of chemicals.
However, the all-in-one terahertz taste sensor has some
limitations or drawbacks, such as long-term stability
problems of the laser power output and the non-uniform
initial potential of the terahertz semiconductor chip causedby the manufacturing process. It requires specialized
equipment and trained personnel to operate, which may limit
its use under certain conditions. Therefore, future researchand development could focus on maintaining the stability of
the laser power output, improving the manufacturing processof the terahertz semiconductor chip, reducing the cost of the
optical setup to make it more accessible, and integrating thesensor for ease of use. In addition, the development ofadvanced data processing or machine learning algorithms isnecessary to achieve more reliable and accurate
measurements.
In summary, the all-in-one terahertz taste sensor shows
great potential for both academic research and industrial
applications, and its non-invasive, label-free, and multianalyte sensing approach will be a major advancement intaste sensing technology. It also has potential for use inenvironmental monitoring, nutrition evaluation, metaboliteand drug measurement, biomarker sensing, and even forodorant identification, which could provide a comprehensive
view and status and contribute to the future Food Data Bank
(FDB).

Author contributions
J. W. wrote the manuscript. K. S. and T. K. reviewed themanuscript. All the authors provided permission for
submission.

© 2023 The Author(s). Published by the Royal Society of Chemistry

Perspective

Conflicts of interest
There are no conflicts to declare.

Acknowledgements
This work was partially supported by a JSPS KAKENHI Grantin-Aid for Early-Career Scientists (grant number: 21K14169).

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