Recent advances in development of electrochemical biosensors for the detection of biogenic amines

Abstract

Biogenic amines (BAs) are widely found in food as a consequence of diverse factors including free amino acid availability, microbial production of decarboxylases, and variations in processing and storage conditions. Hence, BAs are considered as an important marker for determining the freshness and quality of food. Owing to the documentation of BAs in different dietary products, their numerous negative impacts on human health have reported to be a serious concern in past few decades. Therefore, the quantification of these chemical species in food becomes crucial as it can immensely contributes toward control of new episodes on food intoxication in humans. In this line, various chromatographic and colorimetric methods have been developed to detect BAs. However, these methods are in use from a longer time, still are limited by high cost, lengthy procedures, huge infrastructure and skilled personnel requirements that hinder their on-field application. In pursuit of a reliable method offering accurate detection of BAs, this review presents the state-of-the-art of electrochemical strategies for BAs sensing in food. The core of the review discusses about the widely employed electrochemical transducers, such as amperometric, potentiometric, impedimetric and conductometric-based BAs biosensors with significant findings of research work conducted previously. The application of electrochemical sensors to analyze BAs in different fields including food systems (fermented and non-fermented types) and smart packaging systems has been reviewed. Moreover, existing challenges and further available prospects for the development of rapid, facile, and sensitive electrochemical strategies for on-site determination of BAs have also been discussed.

Introduction

Biogenic amines (BAs) are low molecular weight, aliphatic or heterocyclic (aromatic) bases that participate in a range of biological processes (Bachrach 2005). They can be found in various kind of food products including fermented food (Park et al. 2019), meat (Zhang et al. 2019), seafood (Hu et al. 2012), dairy (Novella-Rodríguez et al. 2002), alcoholic beverages (Nalazek-Rudnicka and Wasik, 2017; Gagic et al. 2018), (beer and wine), soy, fruits and vegetables (Czajkowska-Mysłek and Leszczyńska 2017) at varying concentrations (Landete et al. 2007; Naila et al. 2010). BAs are typically formed by microbiological decarboxylation of its precursor amino acids (Dong and Xiao 2017) or via amination and transamination of ketones as well as aldehydes found in microbes, animals and plants. Chemically, these are organic, polycations with aliphatic such as putrescene (Put), spermine (Spm), spermidine (Spmd), and cadaverine (Cad) and aromatic structures such as tyramine (Tyr) and phenylthylamine (PEA), tryptamine (Tryp) and histamine (His) (Önal 2007). Put, His, Tyr, PEA, Cad, Trypt, Spdm and Spm are the main food-related BAs, while among these Put, Cad, Spm, Spdm have large distribution in the human body (Santos 1996).

Different types of BAs have great significance associated with them. Their role is important for physiological functions and biological processes, such as immune response, inflammatory process, gastric secretions (Özogul and Özogul 2019), cell growth, integration, proliferation and stabilization of lipids and proteins, brain development, DNA damage inhibition, nuclear control and gene expression in all living organisms (Ramani et al. 2014). However, several such amines are considered as a serious risk to humans at higher concentrations. The ingestion of BAs can cause nausea, hypertension, hypotension, renal impairment, heart arrhythmia, migraines, brain haemorrhage, and even fatality (Ramani et al. 2014; Verma et al. 2020). Figure 1 shows a schematic diagram illustrating microbial enzymes catalyzed production of biogenic amines along with their harmful impacts.

Fig. 1.

Schematic diagram illustrating microbial enzymes catalyzed production of biogenic amines and their harmful impacts

Numerous food items including fish, drinks, meat, fermented foods and vegetables are well-known to contain high quantities of a diverse range of BAs (Lopez et al. 2017). This higher level of BAs in food is further responsible for causing serious food defects/spoilages and toxicity issues. Presence of histamine in fish “scombroid poisoning,” (Murray et al. 1982), tyramine in cheese "cheese effect" or "cheese reaction" and Put, Cad in foods are well-known to cause serious food poisonings (Pastore et al. 2005). Food toxicity of many such BAs is due to their inhibitory activity toward different types of enzymes, such as diamine oxidase (DAO), polyamine oxidase (PAO), histamine methyl transferase (HMT) etc. BAs are also known to induce nitrite-related reactions in foods resulting in formation of carcinogens (Hernández-Jover et al. 1997; Eerola et al. 1997). Moreover, presence of BAs in foods has also been reported to adversely affect the aroma and taste of food (Wunderlichová et al. 2014). Existing reports have clearly reveal the inherent heat stability of BA which further complicates their eradication even during heat processing of food items. Furthermore, concentration of BAs have been found to be nearly same in the finished product as it was for raw material (Ruiz-Capillas and Herrero 2019). Due to aforementioned reasons, BAs are also considered as potential markers of cancer, food freshness, food quality and extent of microbial spoilages (Draisci et al. 1998; Lange and Wittmann 2002; Rokka et al. 2004; Kaneki et al. 2004; Castilho et al. 2005; Mureşan et al. 2008;).

Keeping in view, the ill effects of BAs especially their role in degrading quality and safety of food have forced international regulatory bodies to set their permissible limits for foods. As per US Food and Drug Administration, a concentration of 500 ppm has been accepted as a serious danger (US FDA 2011). However, a maximum concentration of 0.75–0.9 g/kg for BAs is set as the safety range for Put, Tyr, Cad and His. For these reasons, regulatory bodies, such as the European Commission (EC) Regulation (EC 2073/2005) (Di Fusco et al. 2011), are also becoming increasingly acceptable in investigating the amounts of BAs in foods and beverages.

Permissible standards laid down by above regulatory bodies clearly indicates an urgent need of BAs detection in foods to comply the same. However, the analysis of their trace amounts in a complex dietary matrix (Mureşan et al. 2008) presents several associated challenges. Although, various analytical approaches, chiefly capillary electrophoresis (Steiner et al. 2009; Li et al. 2012), thin layer (Romano et al. 2012; Martin et al. 1987), Gas (Laleye et al. 1987; Marks and Anderson 2006), ion exchange (Standara et al. 2000), high performance liquid and cation exchange chromatography (Pastore et al. 2005; Cinquina et al. 2004; Saccani et al. 2005) and laser desorption/ionisation spectrometry with matrix (Su et al. 2015), offering quantitative analysis of BAs in foods are available. However, at the same time, they have serious drawbacks associated with their application, such as lengthy sample pre-treatment steps, technical expertise, man-power requirements, equipment cost and huge infrastructure installation etc. This highlights the need and paramount importance of development of rapid, cost-effective and user-friendly analytical tool for detection of BAs (Kaçar et al. 2020). Unlike the above, one such rapid technique is biosensing.

Biosensing is a novel, precise, efficient, and automated method that provides an immediate, accessible, and cost-effective approach offering detection of several analytes, including BAs (Bóka et al. 2012). Till date, various biosensing element such as enzymes, microbes, organelles, cells, or tissues, antibodies, receptors, and nucleic acids have been explored for their use to sense BAs. Among currently available biosensors for BAs analysis, electrochemical biosensors of both enzymatic and non-enzymatic types are holding leading positions. Among enzymatic electrochemical biosensors, chiefly those based on amine oxidases from different sources have been explored more in recent past (Santos 1996). Similarly, non-enzymatic biosensor mainly making the use of poly neutral red (Kumar et al. 2021), TiO2-Ag/polypyrrole (Erdogan et al. 2018), nafion-coated copper phosphate electrodes (Lee et al. 2018), tungsten trioxide nanoparticles (Anithaa et al. 2021), carbon dots-functionalized gold nanoparticles (Amiri et al. 2019) and chameleon stain Py-1 (Steiner et al. 2009) have also been proved as a competent alternative for tracing BAs in real samples.

The current article is an attempt to give a comprehensive review of recent advances in developments of different types of biosensors for the detection of BAs using electrochemical means along with special emphasis on their application to analyze BAs in different fields including food systems (fermented and non-fermented types) and smart packaging systems. Moreover, it also provides the insights into existing challenges and future prospects that paves the way to carry out further research to achieve their industrial applications for BAs detection in diverse range of food items.

Biogenic amines (BAs): types and forms

There are different criteria used to classify BAs. These criteria mainly include chemical structure, number of amine gps, route of synthesis and physiological functions. Chemically, BAs are of diverse nature. On the basis of their chemical properties they can be classified as aromatic, aliphatic or heterocyclic organic bases of low molecular weight. According to the precursor amino acids, many amines have been named Tym from Tyr, Him originates from His, and Tryp from Trp etc. (Glória and Vieira 2007).

BAs can exist in three different forms depending on their availability: (i) they can be electrostatically free, (ii) electrostatically coupled to negatively charged molecules, or (iii) conjugated as cinnamic acids, such as caffeic, ferulic, and p-coumaric acids. They have been known to play important roles in promoting growth, development and biotic/abiotic stress response in plants (Bouchereau et al. 1999; Walters 2003). For instance, the plant hormones phenyl acetic acid and indol-3-yl-acetic acid derived from and phenylethylamine and tryptamine, respectively (Coutts et al. 1986). Furthermore, BAs are of vasoactive or neuroactive types. Neuroactive amines such as serotonin and histamine influence the central nervous system through acting on neural transmitters. On the other hand, vasoactive amines affect the vascular system either directly or indirectly.

Significance of biogenic amines

Till date, various studies have documented both the positive and negative impacts of varying types and levels of biogenic amines on human and animal health. BAs perform various type of metabolic and physiological functions including cell growth and proliferation, regulation of immune responses, blood pressure, nutrient intake, neural transmission, allergic response, and the synthesis of alkaloids and hormones, stabilization of DNA's negative charge, protein synthesis, stress resistance and apoptosis (Larqué et al. 2007; Igarashi and Kashiwagi 2010; Plenis et al. 2019). Some amines act as precursors of compounds having biological importance. On the other hand, others, for instance, spermine deficiency results in a polyamine deficiency syndrome, called as Snyder–Robinson syndrome. It is an X-linked form of mental retardation disorder which occur due to a defect in spermine synthase gene (Cason et al. 2003). Mild to moderate mental retardation, osteoporosis, decreased spermine synthase activity, thin habitus, cerebellar circuitry dysfunction, kyphoscoliosis, facial asymmetry, hypotonia correspondingly low intracellular level of spermine in fibroblasts and lymphocytes, and elevated spermine/spermidine ratios are different symptoms in affected males (Cason et al. 2003). BAs could also stimulate the formation of free radicals to expand exponentially, causing oxidative damage (Bjelakovic et al. 2010). To our knowledge, understanding of the role of BAs has now been explored at a level, where they could be beneficial as well as detrimental for maintaining good health of living organisms.

Regulations and detection of BAs

Keeping in view, the aforementioned importance and toxicological impacts of BAs, several regulatory bodies have given permissible/acceptable limits to check the level of BAs in different food matrices (Table 1). The specific standards have been only introduced for histamine by most of the regulatory bodies and no any limits have been set for other type of BAs for different food types, such as meat, dairy, or other products. However, usually the same standards as applicable to fish is applied for other food products also (Ruiz-Capillas and Herrero 2019). Hence, it indicates an urgent need for detection of BAs to determine their actual level present in particular food item (Lopez et al. 2017). In a study, Tyr toxicity threshold level for cheese has been reported to be 100–400 ppm; however, no law to limit this value has been proposed (Burdychova and Komprda 2007; Mercogliano et al. 2010). However, a safety range of 750–900 ppm has been established for total BAs, which includes Put, Tyr, Cad, and His (Gezginc et al. 2013). Examining BAs levels in food and drinks is increasingly being mandated by regulatory bodies, such as the EU Commission Regulation (Di Fusco et al. 2011). BAs are well-known to serve as potential markers for detection of cancers and quality and freshness of a wide variety of food products (Compagnone et al. 2001; Castilho et al. 2005; Carelli et al. 2007; Mureşan et al. 2008). Hence, highly selective and sensitive detection of BAs is highly needed to comply the above mentioned standards for BAs. Till date, numerous conventional analytical approaches including chromatographic methods such as TLC (Lange and Wittmann 2002; Romano et al. 2012), cation-exchange chromatography (CEC) (Pastore et al. 2005; Saccani et al. 2005), capillary electrophoresis (CE) (Steiner et al. 2009; Li et al. 2012), HPLC (Bockhardt et al. 1996; Gatti et al. 2012), GC (Laleye et al. 1987; Ishimaru et al. 2019; Nadeem et al. 2019), ion exchange chromatography (IEC) (Standara et al. 2000; Cinquina et al. 2004), matrix-assisted laser desorption/ionization mass spectrometry (Marks and Anderson 2006; Su et al. 2015), Raman spectroscopy (Li et al. 2020), colorimetry (Patange et al. 2005), fluorimetry (Adamou et al. 2005) and Ion Mobility Spectrometry (IMS) (Parchami et al. 2017) are available to detect BAs. Although these methods are used since long ago to detect BAs, but at the same time they have certain limitations, such as: low specificity, poor sensitivity, long analysis period, skilled personnel required to operate, complex high potential and expensive instrumentation etc. In addition, the handling of different sample quantities is increasingly challenged by the necessity for time-consuming sample pretreatment processes and derivatization. Owing to the documentation of above listed methods, recently some rapid methods including biosensors, chemosensors and immunoassays have also been explored by different researchers.

Table 1.

Legal limits set by regulatory bodies for biogenic amines in different types of food

Regulatory body	Biogenic amine (s)	Food	Set Limits	References
European Commission Regulations (2073/2005, 144/2007, 365/2010)	Histamine	Fish species of Scombridae, Clupeidae, Eugraulidae, Coryphenidae, Pomatomidae, and Scomberesocidae families	Safety limit—100–200 mg/kg; Maximum limit—200 mg/kg	Ruiz-Capillas and Herrero (2019)
		After processing (brine, enzyme maturation, curing, etc.) of fish species of above families	Safety limit—200–400 mg/kg Maximum limit—400 mg/kg
Canada, Australia and New Zealand standard codex feature	Histamine	Fish	Maximum limit— 100–200 mg/kg	FS Australia, New Zealand; CFIA
U.S. Food and Drug Administration	Histamine	All type of food and food products	50 mg/kg	US FDA (2011)
Eurasian Economic Union, (Armenia, Belarus, Kazakhstan, Kyrgyz, and Russia) TR EAEU 040/2016	Histamine	Tuna, mackerel, herring, salmon fish and their food products	100 mg/kg is	Müller et al. (2022)
Slovak Republic	Tyramine	Cheese	200 mg/kg Regulatory limit	Neofotistos et al. (2019)
	Histamine	Beer	20 mg/L Regulatory limit
Other Countries	Histamine	Wine	2 mg/L (Germany); 5–6 mg/L (Belgium); 8 mg/L (France); 10 mg/L (Switzerland) Regulatory limit

The current articles presents a comprehensive review on the recent advances in development of biosensing technology chiefly electrochemical types to detect BAs.

Biosensors: principle and components

The interaction of biological components with a specific analyte (the substance to be detected in the sample) and the creation of physicochemical changes are the fundamental principles upon which biosensors are based. Biosensors are simple, robust, and cost-effective analytical systems that signals the presence or absence of any analyte usually on the basis of transfer of electrons or heat, change in pH and mass, absorption or release of particular ions or gases. All type of biosensors include two main components (i) biorecognition element and; (ii) transducers and processors. Biorecognition elements mainly include enzymes, whole cells, antibodies, nucleic acids/aptamers and plant tissues etc. These biorecognition components are actually responsible for identifying target analytes and subsequent amplification, processing, and translation of the resulting signal into a readable format is achieved by means of transducer. In case of electrochemical biosensors, the resultant signal is converted into a quantifiable electronic signal by the transducer and the strength of the signal generated is directly proportional to the concentration of the target analyte that is located in close proximity to it. Electrochemical biosensors now holding leadership among the currently available biosensing systems for BAs analysis due to their great performance, simple design, rapid screening procedures, low cost, low detection limits or higher sensitivity and the possibility of downsizing (Lopez et al. 2017). Furthermore, among electrochemical biosensors, in particular, enzymatic amperometric biosensors have gained more importance over the course of the past 10 years (Henao-Escobar et al. 2013). These devices make the use of enzyme selectivity to identify an analyte with the direct transduction of the rate of the biocatalytic reaction into a current signal (Freire et al. 2003). As a result, enzymatic biosensors have received a considerable amount of attention in the electroanalysis of BAs in recent years, as can be shown in Table 2. After years of development in the laboratory, biosensors are finally being put to use in the field, and several of them have already been brought to market (Sharma et al. 2003). The present review presents extensive review of different types of electrochemical biosensors for BAs detection, which cover a diverse range of fabrication processes and materials.

Table 2.

Recently developed electrochemical biosensors for detection of biogenic amines with analytical figures of merit

Bio recognition element	Transducer construction	Type of biogenic amine	Detection limit	Linear response range	Response Time	Storage Stability	References
Amperometric
Diamine oxidase	DAO-nPt/GPH/CHIT/CSPE	Histamine	2.54 × 10–8 M	0.1 to 300 uM	60 s	30 days	Apetrei and Apetrei (2016)
Calcium phosphate materials	Brushite cement-PPO-GA	Tyramine	4.85 × 10−8 M	5.8 × 10−7 to 1.6 × 10−5 uM	6 s	7 days	Lopez et al. (2017)
Polyamine oxidase	PAO/CHIT/Zeolite-AuNPs/Au	Spermidine	0.1 μM	0.2–200 μM	5 s	> 180 days	Chauhan et al. (2017)
Putrescine oxidase	PUOD/POD/KB/AuMDE	Putrescene	5 μM	17 to 500 μM	5 s	NR	Xia et al. (2017)
Free enzyme	Cu Electrode	Histamine	0.33 μM	1 to 750 μM	NR	28 days	Lin et al. (2018)
Tyrosinase	Ty/Fe3O4-CH/PLL/SPCE	Tyramine	7.53 × 108 M	4.93 × 107 to 6.33 × 105 M	NR	7 days	Dalkıran et al. (2019)
Tyrosinase	Poly(MPAA)/CGL	Tyramine	3.16 μM	10 to 60 μM	5 s	35 days	Soares et al. (2019)
Diamine oxidase	DAO/ITONP/PB/SPCE MAO/	Histamine	2.7 × 10−6 M	6.0 × 10−6 to 1.0 × 10–3 M	40 s	NR	Kaçar et al. (2020)
Monoamne oxidase	ITONP/PB/SPCE	Cadaverine	8.9 × 10–3 M	3.0 × 10−6 to 1.0 × 10−3 M
Diamine oxidase	DAO/GA/SPCE	Histamine	0.97 ppm	5–75 ppm	NR	35 days	Torre et al. (2020)
Diamine oxidase	DAO/HRP/ LDH/Mg2AlCO3	Histamine	< 10–8 M	10–8 to 10–3 M	< 20 s	> 10 days	Hidouri et al. (2021)
Diamine oxidase	DAO-CS-AuNPs/PB/MWCNTs/SPCE	Histamine	1.81 μmol L–1	2.5–125.0 μML–1	NR	35 days	Nontipichet et al. (2021)
Peroxidase	Apt/AuNFs/ITO	Histamine	0.79 nmol L−1	1 to 5000 nM L−1	Few s	> 30 days	Xu et al. (2022)
Potentiometric
Direct recognition	DAO/HRP	Tyramine	5.8 × 10−5 M	1 × 10−2 to 7.74 × 10−5 M	5–10 s	NR	Draz et al. (2021)
Affinity	DAO/HRP	Histamine	25 mM	0 to 500 mM	20 s	NR	Minamiki and Kurita (2019)
Diamine oxidase	DAO/HRP	Histamine	10–8 M 1 µM	10–8 to 10–3 M	< 8 s	NR	Ma et al. (2021)
Impedimetric
Tyrosinase	Brushite cement-PPO-GA	Tyramine	4.85 × 10−8 M	5.8 × 10−7 to 1.6 × 10−5 M	6 s	7 days	Lopez et al. (2017)
Molecularly imprinted polymer	MIP-CP electrode	Histamine	7.4 × 10−11 M	7 × 10−9 to 4 × 10−7 M	5 s	20 days	Akhoundian et al. (2017)
Tyrosinase	AuNP-PANSA	Tyramine	0.04 µM	0.8 to 80 µM	NR	NR	da silva et al. (2019a; b)
Tyrosinase	SELEX/ELONA/ EIS	Tyramine	0.71 µm	10 to 120 µM	NR	NR	Ho et al. (2020)
Molecularly imprinted polymer	Au/Cys/MIP	Histmine	2.1 × 10−7 M	5.0 × 10−7 to 1.0 × 10−3 M	NR	NR	Serrano et al. (2020)
Schiff base	Nano-TiO2/FTO	Histamine	4.6 × 10 − 8 M	1.0 × 10−7 to 1.0 × 10−2 M	NR	180 days	Sahudin et al. (2021)

NR not reported

Electrochemical biosensors for the detection of BAs

An electrochemical biosensor is defined as sensing platform that make the use of a biorecognition element and an electrochemical transducer. Biorecognition elements induces a biological event or response in the presence of analyte. The generated response can then be followed by its capturing by sensing transducer, as shown in Fig. 2. Electrochemical biosensors convert analyte–sensor interactions into electrochemical signals. In the literature, there are four types of electrochemical biosensors, i.e., amperometric, potentiometric, impedimetric and conductometric which have been employed for BAs detection.

Fig. 2.

Schematic diagram showing working principle of electrochemical biosensors

Amperometric

Amperometric transducers works on the principle of measuring the electric current when an electric potential is applied through an electrode. Their properties are mostly determined by the physicochemical properties of the material used in the transducers as well as the mode of immobilizing the enzyme used as biosensing element (Singh et al. 2009; Vasconcelos et al. 2021). Then, various studies are presented in which amperometry is used as the basis for these investigation demonstrate the device’s versatility, ranging from the determination of BAs in the blood/serum samples of rat to culinary samples, such as pickled vegetables and fish etc. Table 2 covers many such amperometric biosensors developed till date for targeting BAs detection. A biosensor has also been developed to determine the total BAs present in samples of rat blood. Bovine serum albumin, glutaraldehyde and carbodiimide were used to immobilize horseradish peroxide on graphite and the LOD was 17 mg/mL. Since it enables rapid analysis with no sample pretreatment, this biosensor is a good replacement for conventional techniques (Castilho et al. 2005). On a carbon electrode that was screen-printed with MAO/tetrathiafulvalene and MAO/gold nanoparticles, two working electrodes were developed as an amperometric biosensor to detect PUT and CAD. For PUT and CAD, this BS demonstrated detection capabilities of 9.9uM and 19.9 + 0.9Um, respectively (Henao-Escobar et al. 2013). In a different method of detection, glutaraldehyde trapped DAO rather than MAO onto an electro-synthesised bilayer membrane. The sensitivities obtained this sensor. HIS, PUT, and CAD had values of 2.65 ± 2.2, 114.2 ± 3.0 and 57.5 ± 2.1 (nA/mM). the biosensor worked well in both correct and incorrect preserved fish samples (Torre et al. 2019). Recently reported research uses a screen-printed carbon electrode and DAO to detect His (Apetrei and Apetrei 2015). Enzymes were co-immobilized onto a polysulfone/carbon nanotube/ferrocene membrane utilising a phase inversion screen-printed electrode. With a low LOD of 1.7 × 10–7 M. The use of carbon nanotube for TYM detection has also been proposed (Pradela-Filho et al. 2021). According to the results of the study, it is possible to produce a biocompatible matrix for the immobilisation of tyrosinase by employing a modified screen-printed electrode carboxyl functionalized with single-walled carbon nanotubes and an amperometric-based biosensor. Screen-printed nanotube electrodes with thick film electrodes were cast using the casting process, and then glutaraldehyde was used to cross-link the electrodes. The limit of detection for biosensor was 0.62 um. Past studies have shown that this biosensor can identify Tym in smoked fish and pickled samples. This study developed a novel electrochemical method for the detection of tryptamine, employing a microfluidic system based on paper and an amperometric detector made of thermoplastic electrode. Surprisingly, the authors assert that more ascorbic acid from an alkaline sample can be oxidised at higher concentrations of oxygen (compressed air). Ascorbic acid must be removed from an alkaline sample in greater amounts. This simple approach appears to be effective in removing ascorbic acid peaks from the chronoamperogram of the amperometric sensor (Torre et al. 2019). It was found that the amperomatric biosensor may be utilised to determine the interference properties of amino acids in food matrixes. The response of the biosensor was tested by making a comparison between the signal produced for a 0.04 M BAs standard solution and the signal obtained for solutions of the same concentration of the amino acids that were utilised in the study and are naturally involved in the production of BAs. This was done to determine how well the biosensor responded. The introduction of the amino acids histidine and lysine in the real sample drastically altered the biosensor response for MAO and DAO (Draz et al. 2021). A glutaraldehyde-based method can be used to immobilise the enzymes utilised to detect PUT, CAD, HIS, and tyrosine on a variety of electrodes, such as those described above. As per literature, amperometric biosensors have been proved to be efficient in detection of BAs such as histamine in a highly sensitive and selective way without requiring any type of lengthy steps for preparation of sample (Gajjala and Palathedath, 2018). However, performance of enzymatic amperometric biosensor has found to be sometimes adversely affected by the method selected for immobilization of enzyme. Therefore, the stability and sensitivity of such biosensors can only be improved using an appropriate immobilisation method (Mentana et al. 2020).

Potentiometric

The working principle of potentiometric biosensors is based on the detection of a change in the electrode's electric potential after coming in contact with a particular analyte (Yin and Qin 2013). It is used to measure the intensity of signal. A measurable potential or charge accumulation is determined (Bratov et al. 2010). A reference electrode and an indicator electrode are included in these system. Commercially, available potentiometric sensors include glass coated and ion-selective electrode as well as metal oxide electrode, which are subset of the potentiometric sensors, the almost of which is a pH-sensitive glass electrode (Koncki 2007).The signal is generated by charge separation at the interface between the ion-selective membrane and the solution. This is because of the selective partitioning of ionic species that occurs between these two phases (Bratov et al. 2010).The inclusion of MIPs in poly(vinylchloride)membranes was previously reported as a potentiometric sensors for HIS detection in the wine and fish samples (Basozabal et al. 2014).The LOD was attained 1.12 × 10–6 mol/L. The researchers came to the conclusion that the label-free detection of histamine in real samples was feasible due to the utilisation of nanoparticles that possessed affinity and high levels of specificity. For the purpose of detecting BAs, an artificial receptor in the form of a water electrode that has been functionalized with a SAM of 4-mercaptobenzoic acid was used. The carboxylate group is able to detect the presence of the amino group through the use of hydrogen bonding and electrostatic interactions. This procedure resulted in LOD of 25 nm (Minamiki and Kurita 2019).Solid-state potentiometric sensors for TYR detection were developed just, so that TYR could be used solely to identify meals. The impact of each element was assessed during the sensor optimization process. Interferences of different cationic species were assessed using the separate solution method to measure potentiometric selectivity coefficient. Lower the value, higher the target ion selectivity. These coefficient were discovered to be tiny enough demonstrating the potentiometric sensor’s TYR selectively. Potentiometric biosensors constitute the most extensively used cost-effective analytical device in today’s time. Their use offers several advantages such as high sensitivity, selectivity, lower limit of detection with high accuracy and ease of miniaturisation and automatic operation (Kamel 2015; Hassan et al. 2018). Various potentiometric biosensors developed to detect BAs have been listed in Table 2.

Impedimetric

Impedimetric transducer detects the conductor’s conductive qualities (more accurately, its impedance) medium as a function of the concentration of the analyte (Vasconcelos et al. 2021). Electrochemical impedance spectroscopy (EIS) integrates the investigation of both capacitive and resistive properties of material using a sinusoidal excitation voltage signal to perturb a system at equilibrium. The motion of ions and electrons is resisted by all of the components contained within the electrochemical cell (such as capacitors, resistors and inductors) which causes a fluctuation in the impedance of the circuit (Guan et al. 2004). A frequency-dependent change in an electrochemical cell's impedance that is generated by a redox biological reaction is monitored (Prodromidis 2010; Uygun and Uygun 2014). It is a method for analysing the kinetics of the electrodes as well as the characteristics of the analyte binding to the electrodes. For the purpose of EIS measurement, an alternate current known as I(t) is used, and simultaneously, an electrical potential known as V(t) is produced with a phase that is distinct from that of the current (Prodromidis 2010).With EIS, a wide frequency range can be used to measure the impedance of a biological reaction at the electrode surface. Many different biomolecules have been tried and tested in the role of fundamental detecting elements in impedimetric biosensors, with variable degrees of effectiveness (Uygun and Uygun 2014).To produce a sensor for the detection and measurement of TYM, the enzyme tyrosinase was first immobilised in a substance composed of calcium phosphate, and then the material was cross-linked using glutaraldehyde. 4.85 × 10^–8 M was determined to be the LOD for the brushite cement-polyphenol oxidase-glutaraldehyde-based biosensor. The TYM content in cheese samples was determined used the suggested biosensor (Lopez et al. 2017). For the research and development of a voltametric basis standard for the detection of HIS in serum samples, the utilisation of MIPs embedded into a carbon paste (CP) electrode as an MIP-CP electrode detector system was investigated and developed. The LOD that could be obtained with this sensor was 7.4 × 10–11 M. (Akhoundian et al. 2017). To build a sensor for TYM detection, a nanocomposite film (made up of polymer and gold NPs) was modified using a gold electrode. To locate TYM in fermented beverages and dairy products, it has been applied. This approach had a LOD of 0.04 uM (Silva et al. 2019a; b).Furthermore, the LOD for TYM detection was 0.71 uM. When using the same immobilisation; however, this time for tyrosinase immobilisation, the results were significantly higher than those found in the earlier studies (Silva et al. 2019a, b).For selective detection of HIS, another study indicated that an impedimetric-based aptasensor was helpful. These aptamers can bind histamine, making them useful as bio-recognition agents and for assessing histamine levels in food samples (Ho et al. 2020).The adaptability of this form of BS is clear from the examples shown above. They can detect or measure distinct BAs using the same detection method. In the research that was summarised, a variety of methods were applied; for instance, calcium phosphate materials were utilised, and then glutaraldehyde cross-linking was performed thereafter. The LOD was discovered to be relatively low in the majority of the experiments.

Because of this, the biological component's final signal is a function of analyte concentration. Immobilized amino oxidases (AOs), which are responsible for the biocatalytic oxidation of PAs, are utilised in a number of different electrochemical biosensors of PAs. The enzymatic reaction generates hydrogen peroxide, which can be measured with a working electrode. For example, flexible electrochemical biosensors have been applied in a variety of food samples. One of the most commonly used bi-enzymatic biosensors is one that uses a second enzyme to biocatalyze its own enzyme products. When the second enzyme's enzymatic activity is detected by the working electrode, it will show whether redox species are being synthesised or consumed. A limited number of injection analysis (FIA) systems incorporate specific electrochemical biosensors for PAs. It is essential that a sample be injected into the flow of liquids in an FIA system for it to work. Because of their rapid sample throughput, small sample volume, and short analyte interaction time, these devices have several distinct benefits over more traditional analytical methods (Vasconcelos et al. 2021). Table 2 lists out many such biosensors for detection of BAs.

Conductometric

The working of conductometric transducers is based on the sensing of conductivities resulting from biological processes. As the conductivity, i.e., the reciprocal of resistivities, can alter according to the biological processes or biochemical reaction. This method uses two parallel electrodes to measure the conductivity of a sample solution (Adley and Ryan 2015). For this reason, it is possible to make a low-cost, huge quantities of biosensors utilising low-amplitude alternating voltages, without the usage of a reference electrode, and without the need for light sensitivity. Other advantages of biosensors based on this phenomenon include the following: Various reactions and methods can be used to determine a wide range of analytes of various types, and the driving voltage can be kept low to minimise the amount of power required. It's possible to use thin-film technologies to include them into the design. They can be integrated using standard thin-film technology; a variety of reactions and processes can be employed to identify a wide range of analytes; and the driving voltage can be low enough to significantly minimise the power consumption (Schaudies 2014). BAs such as CAD, PUT, AGM, HIS, TRY, and TYM were found using a capillary electrophoresis approach with conductometric detection (Kvasnička and Voldřich 2006).The six BAs were clearly differentiated by a detection limit of 2–5 m. Using calixarenes as a conductometric biosensor, Sovovska et al. proposed a novel approach of detecting BAs (Sosovska et al. 2009) There were employed thin-film interconnected planar electrodes, which were doped with macrocycles such as C benzyl resorcinol calixarene (Ladero et al. 2010) or p-tert butylcalix (Landete et al. 2007) arene. The optimal calixarenes concentration for the tested biosensor membranes was found to be 0.25 mg/mL, according to the results. Conductometric sensors have been used to detect BAs that are more closely linked to degradation, despite the fact that the tests described were not the most recent (PUT, CAD, and HIS).

Applications of electrochemical biosensors for analysis of BAs in diverse fields

The sensitivity level of developed biosensors to detect BAs varies according to their field of application. The performance of BAs biosensors is mainly dependent on: the type of bio recognition element and physicochemical properties of transducer employed in biosensing and; type of food as each food has a unique profile of amino acid that further determines the extent of formation of BAs. Below given studies show the diverse applications of electrochemical biosensors for the detection of BAs in diverse range of non-fermented to fermented foods and packaging systems.

Food system

Various type of food including non-fermented such as fish, meat, milk, fruits, and vegetables and fermented such as wine, beer and cheese etc. are rich in amino acids (Vasconcelos et al. 2021). Under poor temperature and other storage conditions, they easily undergo spoilage chiefly due to microbial decarboxylase activity with resulting increase in BAs concentrations. Therefore, quantification of BAs has been considered as an important indicator to evaluate the shelf-life and freshness of different food items. Keeping in view, in past few decades numerous electrochemical biosensors showing varying level of BAs sensitivity have been developed to assess the level of BAs in diverse food types including those of fermented and fermented types as discussed below.

Fermented foods

In past few years, various studies have documented the development of biosensors chiefly of electrochemical type for targeting the detection of different types of BAs in diverse range of fermented foods and beverages. An electrochemical biosensor for trimethylamine detection was constructed using a nanocomposite film, made up of polymer and AuNPs, modified gold electrode. The developed sensor showed a detection limit of 0.04 µM and has been successfully used to detect TYM in dairy products and fermented drinks (Silva et al. 2019a, b). Apetrei and Apetrei (2013) also reported the development of a tyrosinase-based electrochemical biosensor for targeting the detection of tyramine levels in sauerkraut. To develop the sensor, tyrosinase was immobilized on the Pt electrodes using polypyrrole (PPy) as a cross-linking matrix. The detection mechanism is based on the electrochemical oxidation of o-quinone derivative (dopaquinone) through dopamine (4-(2-aminoethyl)benzene-1,2-diol). With this sensor, 95% of steady state response was achieved in 5 s, indicating rapid electron transfer kinetics. The developed sensor was found to be stable with more than 85% of current response even after 8 weeks of storage under refrigeration at 4 °C. Another study developed an amperometric biosensor for measuring tyramine in beverages and fermented milk products. The biosensor architecture immobilises tyrosinase on a gold nanoparticle- and polymer-modified glassy carbon electrode (8-anilino-1-naphthalene sulphonic acid). Under optimal conditions for fixed potential amperometric detection, the biosensor record a LOD of 0.71 µM. It was selective, stable, and reproducible. The tyramine biosensor measured Tyr in beverages (beer and red wine) and in and in dairy products (yogurt and Roquefort cheese) with good recoveries. The recoveries ranged from 93 to 97% with RSDs less than 2.5%, proving the method's reliability for food safety applications (Silva et al. 2019a; b). Similarly, many other studies have also documented the development of various type of electrochemical biosensors for highly sensitive, rapid and cost-effective detection of BAs in many other type of fermented foods.

Non-fermented foods

Recently, several electrochemical biosensors using different transducer systems have been developed to detect BAs in diverse range of non-fermented foods of animal and plant origin, such as fish, meat, milk, fruits and vegetables etc. A screen-printed carbon electrode and DAO-based biosensor was recently reported for detection of HIS. Using glutaraldehyde and BSA, enzyme immobilization was done on electrode surface via cross-linking. The developed sensor showed a detection limit of 0.5 mg/L with successful applicability for detection of HIS in real fish extracts (Torre et al. 2019). Chauhan et al. (2017) reported the development of a PAO-based biosensor electrode for the detection of Spmd in fish. Cross-linking with glutaraldehyde was used to immobilise enzymes on the surface of electrodes. The designed sensor demonstrated a detection limit with good reproducibility and stability, as well as its usefulness for Spdm detection in fish homogenates.

Packaging system

Various types of food especially fresh fish, meat and dairy products are highly perishable. Different microbial strains results in varying types of spoilage depending on the temperature and storage conditions (Casaburi et al. 2015). To enhance their shelf-life, several smart packaging systems have been introduced in recent years. These packaging systems further needs—(i) the identification of the keynote quality indicating metabolites; (ii) construction of sensing technologies for target metabolites; and (iii) their use to further determine the shelf-life and communicate the food quality and freshness from the time of packaging until the day food is subjected to spoilage (Kuswandi, et al. 2011; Miller et al. 2021). Among different metabolites, biogenic amines (histamine, tyramine, putrescine, and cadaverine) holds great potential for their use as target metabolite to determine microbial spoilages of different types of packaged foods. One of the major factor determining the quality of food especially fish and meat is freshness that can further be assessed by different methods based on analysis of volatiles (Olafsdottir et al. 1997). As per literature, no any type of electrochemical biosensors, chiefly oxidase, dehydrogenase and tyrosinase types, could detect BAs by vapor recognition approach. As the detection of BAs by enzymatic biosensors is chiefly carried out in solution that further needs mashing and dissolution of food for analysis of BAs concentration. However, a non-enzymatic and non-destructive method based on volatiles analysis has been worked out to determine the freshness of packed cod fillets by Heising et al. (2012). This method works on the principle of volatiles partition in headspace, their dissolution and dissociation in an aqueous phase and their subsequent monitoring by electrochemical means, by Heising et al. (2015). The resulting electrochemical properties of aqueous phase were due to total volatile basic nitrogen content (TVB-N). The concentration of TVB-N is further related to the formation of trimethylamine (TMA), a dominant component of fish undergoing spoilage and results in typical fishy odour (Howgate 2010; Huss 1995). TVB-N has been reported as a good indicator to determine the freshness of various types of marine fish (Botta et al. 1984). This research group further extended this work to develop a mathematical model to predict the freshness of packed fish from the signal generated by sensor based on TMA concentration. Significant outcome reported in this study greatly support the concept of intelligent packaging.

Current progress, challenges and future prospects

Detection of BAs in food is of utmost importance mainly due to the toxicological risks associated with them and possibility of using them as food quality indicator. However, the quantitation of BAs is highly challenging in food system due to several reasons including (i) very low concentration level (sub-ng/mL range); (ii) strong polarity resulting in a greater solubility in water than organic solvent; (iii) complex nature of sample; and (iv) the presence of interfering species such as polyphenols, lipids, proteins etc. in different types of fermented and non-fermented foods (Papageorgiou et al. 2018). This highlights the need of sample preparation and extraction protocols which is laborious and time consuming. To solve this issue, the developed analytical methods usually employ amine extraction and derivation to carry out quantification. These steps adversely affects the total recovery of analyte. Moreover, derivatization is also an undesirable process as it further leads to errors and loss of analyte. Detection of BAs by most of the conventional methods such as chromatography involves the use of different solvents which is not environment friendly and also results in generation of toxic waste product. On the other hand, use of electrochemical methods especially biosensors offer several advantages including; (i) minimum solvent requirement; (ii) ability to run on aqueous solvent (iii) environment friendly due to the use of probe; (iv) easy sample preparation steps; (v) cost-effective as all enzymatic electrochemical sensors can perform analysis in phosphate buffer and are recyclable nature of used electrodes. Though use of electrochemical approach offers faster BAs detection and is a green approach because of being eco-friendly, still it has several limitations (Papageorgiou et al. 2018; Kumar et al. 2020). The working performance of electrochemical biosensors is negatively impacted and impaired by following factors.

• Many BAs are redox inactive type of molecules, and therefore, their direct detection is not possible by electrochemical sensing. Detection of such type of BAs need an electrode with immobilized enzyme.

• Till date, many studies employ three main type of enzymes including oxidases, dehydrogenases and tyrosinase for detection of BAs. Among these, amine oxidases such as DAO and PAO have been most commonly used to target detection of BAs. A serious drawback associated with the use of these enzyme is their temperature sensitivity. Hence, to maintain their activity, their storage at freezing temperatures is mandatory which in turn limits their practical utility for constructing enzymatic electrochemical biosensors for quantifying BAs.

• Application of amine oxidase-based detection of BAs in alcoholic beverages such as wine and beer greatly suffers by the problem of inhibition of amine oxidases by presence of ethanol

• To perform electrochemical sensing-based experiments, there is always the need of instrument. Although, these instruments are portable but always require power pack’s that further make them unfit for on-field applications.

• The use of different types of working electrodes used conventionally to perform electrochemical analysis such glassy carbon electrode, gold and graphite electrodes etc. also suffers from the matrix effect contributed by various type of immobilization agents (Ancín-Azpilicueta et al. 2008; Kumar et al. 2020).

The aforementioned points clearly indicate an immense need of explore the stated factors in future to promote the faster transfer of developed electrochemical technologies to detect BAs from lab prototypes to food industries. To resolve these issues, the use of disposable screen printed electrode (SPE) with immobilized enzyme is a suitable option that could be used to overcome some of these challenges. As SPE are portable, cost-effective, and simple to construct and offer reliable results with enzymatic biosensors in real world situations. Moreover, development of non-enzymatic electrochemical biosensors to target BAs detection could also be worked out as an alternative option by employing molecularly imprinted polymer (MIP) type of strategies in future.

Conclusions

Food security is a crucial necessity for the entire food chain, thus it’s critical to have a thorough understanding of the dangers related to food as well as how it’s processed and handled. In view of the aforementioned issues related to BAs, the detection of BAs in food has become a serious concern in past few decades. Various traditional chromatographic method such as GC, CE, IEC and HPLC are most frequently employed for BAs detection. These methods so have certain drawbacks, such as the need for competent staff to run them and the reagent requirements for sample pretreatment and derivatization. In contrast to all of these technique, biosensors especially those of electrochemical types represent one of the cutting edge, reliable, and automated technology that provide quick, easy and affordable options for BAs detection. Therefore, this article well-described all major types of electrochemical biosensors that have gained great importance as a bioanalytical device for today and tomorrow, since they can overcome challenges associated with detection of BAs using existing approaches by offering higher detection limit, increased specificity and selectivity. Moreover, using nanomaterials, and functionalization with various substances, and immobilisation of enzymes, bacteria and antibodies, biosensors are extremely versatile. In addition, mediators are used to speed up the transport of electrons from the working electrode surface to the enzyme redox centre. Numerous, promising future for biosensor are still being investigated including the use of multifunctional nanocomposite, nanoelectrodes, and nanofilms.

Data availability statement

This article has no additional data.

Declarations

Conflict of interest

Authors declare no any conflict of interest.

Human and animal rights

This work does not involve the use of any Human Participants and/or Animals.