•Detection and screening of bitterness using animal’s gustatory system.•Features of spiking activity as well as LFP are both analyzed.•Fast response and high classification accuracy are achieved.•Interference study is conducted ensuring the high specificity to bitterness.Bitterness detection has attracted increasing attention in science and industry. However, existing methods often suffer from drawbacks such as long detection time and low specificity. Mammalian gustatory systems have been acknowledged as valid chemosensing systems, and thus the potential of utilizing intact rat gustatory system is investigated in bitterness detection and screening. Rat’s gustatory cortex (GC) functions as the central processor of gustation, and GC neurons are coupled with microelectrode array under anesthesia to reduce moving artifacts. By recording extracellular potentials in GC, response patterns evoked by bitterness are widely discovered in both single neuron and neural network activities. As a result, signals are observed to carry abundant information about taste qualities within the first 4 s after bitterness delivery, and the purpose of fast detection is achieved. Based on support vector machine, this biosensor can detect and recognize bitterness with an accuracy of 94.05%. Moreover, the high specificity to bitter compounds is guaranteed by single bitter responsive neuron which can generate highly specific firing patterns in spite of the existence of interference. Quantitative study also reveals that this in vivo system is sensitive enough for further applications. In conclusion, this whole animal-based biosensor is able to detect bitterness especially with strict constrains in time and provides new platform for bitterness screening with high specificity.

•Detection of bitterness using behaving rat's gustatory system and brain–machine interface.•High accuracy in discrimination between bitter and non-bitter substances.•Dependence found between power of LFP oscillations and bitterness concentration.•Detection of bitterness is achieved with high sensitivity and the limit of detection is 0.076 μM.Animals' gustatory system has been widely acknowledged as one of the most sensitive chemosensing systems, especially for its ability to detect bitterness. Since bitterness usually symbolizes inedibility, the potential to use rodent's gustatory system is investigated to detect bitter compounds. In this work, the extracellular potentials of a group of neurons are recorded by chronically coupling microelectrode array to rat's gustatory cortex with brain–machine interface (BMI) technology. Local field potentials (LFPs), which represent the electrophysiological activity of neural networks, are chosen as target signals due to stable response patterns across trials and are further divided into different oscillations. As a result, different taste qualities yield quality-specific LFPs in time domain which suggests the selectivity of this in vivo bioelectronic tongue. Meanwhile, more quantitative study in frequency domain indicates that the post-stimulation power of beta and low gamma oscillations shows dependence with concentrations of denatonium benzoate, a prototypical bitter compound, and the limit of detection is deduced to be 0.076 μM, which is two orders lower than previous in vitro bioelectronic tongues and conventional electronic tongues. According to the results, this in vivo bioelectronic tongue in combination with BMI presents a promising method in highly sensitive bitterness detection and is supposed to provide new platform in measuring bitterness degree.

•A novel cell-based Love Wave biosensor is established to detect Okadaic acid (OA).•The biosensor can monitor the cell attachment and detect the cell response to OA.•This biosensor has a wide linear detection range (10-100 μg/L).A novel HepG2 cell-based biosensor using Love Wave sensor was developed to implement the real-time and sensitive detection of a diarrheic shellfish poisoning (DSP) toxin, Okadaic acid (OA). Detachable Love Wave sensor unit and miniaturized 8-channel recording instrument were designed for the convenient experimental preparation and sensor response signal measurement. The Love Wave sensor, whose synchronous frequency is around 160 MHz, was fabricated with ST-cut quartz substrate. To establish a cell-based biosensor, HepG2 cells as sensing elements were cultured onto the Love Wave sensor surface, and the cell attachment process was recorded by this biosensor. Results showed this sensor could monitor the cell attachment process in real time and response signals were related to the initial cell seeding densities. Furthermore, cell-based Love Wave sensor was treated with OA toxin. This biosensor presented a good performance to various OA concentrations, with a wide linear detection range (10–100 μg/L). Based on the ultrasensitive acoustic wave platform, this cell-based biosensor will be a promising tool for real-time and convenient OA screening.

Cell-based bioassays were effective method to assess the compound toxicity by cell viability, and the traditional label-based methods missed much information of cell growth due to endpoint detection, while the higher throughputs were demanded to obtain dynamic information. Cell-based biosensor methods can dynamically and continuously monitor with cell viability, however, the dynamic information was often ignored or seldom utilized in the toxin and drug assessment. Here, we reported a high-efficient and high-content cytotoxic recording method via dynamic and continuous cell-based impedance biosensor technology. The dynamic cell viability, inhibition ratio and growth rate were derived from the dynamic response curves from the cell-based impedance biosensor. The results showed that the biosensors has the dose-dependent manners to diarrhetic shellfish toxin, okadiac acid based on the analysis of the dynamic cell viability and cell growth status. Moreover, the throughputs of dynamic cytotoxicity were compared between cell-based biosensor methods and label-based endpoint methods. This cell-based impedance biosensor can provide a flexible, cost and label-efficient platform of cell viability assessment in the shellfish toxin screening fields.

•We established two human cancer cell-based impedance biosensors (CIB) to detect DSP toxins in dynamic and real-time way.•Comparative experiments in DSP toxins detection were carried out between CIB and conventional cell-based assay (CCK8).•CIB method presents a good correlation with mouse bioassay (MBA) and LC–MS–MS in DSP toxins detection.Diarrhetic shellfish poisoning (DSP) toxin is a dangerous contamination in seafood worldwide that can threaten human health and fishing. A large number of animal bioassays and chemical analytical methods are employed for DSP toxin detection. However, these toxin detection methods are low-throughput and high-cost which hamper their wide applications. In this study, HeLa and HepG2 cell lines were selected as the sensitive elements to establish the CIBs for monitoring the cytotoxicity induced by a representative DSP toxin, okadaic acid (OA). The limit of detection (LOD) of HeLa- and HepG2-based biosensors are 10.2 μg/L and 3.3 μg/L, respectively, which are both lower than the conventional cell-based assay (21.2 μg/L of HeLa cells and 9.8 μg/L of HepG2 cells). The half maximal inhibitory concentration (IC50) values of OA in HeLa and HepG2 cells which were obtained from CIB (49.9 ± 4.9 and 39.2 ± 4.3 μg/L) are both lower than Cell Counting Kit-8 assay (CCK8) (62.7 ± 7.1 and 45.8 ± 6.7 μg/L). Besides, CIB measurement presents good correlation with mouse bioassay (MBA) and liquid chromatography–tandem mass spectrometry (LC–MS/MS). In summary, all the results indicate that the CIB technology had great potential to be an effective complement in DSP toxins detection.

Herein, we present a novel miniaturized multisensor chip integrated with a nanoband electrode array (NEA) for lead and copper detection and a light addressable potentiometric sensor (LAPS) for pH sensing. By this means, pH information could be provided before electrochemical analysis to ensure high performance in heavy metal quantification due to the significant effects of solution acidity on electrochemical analyses. The fabrication processes of the multisensor chip are described in detail and the electrochemical behaviour of NEA was characterized using cyclic voltammetry in sulfuric acid and acetate buffer. For the detection of lead and copper qualitatively and quantitatively, square wave anodic stripping voltammetry (SWASV) was applied with the standard addition method. Deposition potential and deposition time were optimized to be −0.6 V and 120 s, respectively. NEA exhibited a sensitivity of 0.510 μA pbb−1 and 0.678 μA ppb−1 towards lead and copper, respectively, with high correlation coefficients. The repetitive and long-term experiments also demonstrated the good reproducibility and stability of NEA in heavy metal detection. Moreover, the silicon nitride modified LAPS showed a pH sensitivity of 56.49 mV pH−1 with a high correlation coefficient of 0.9999. The reproducibility of LAPS was also investigated and a deviation of less than 2 mV was obtained in both the samples. These results indicate that the miniaturized multisensor chip demonstrates good electrochemical performance in heavy metal and pH sensing.

With growing concern about human health, relevant drug and food toxicity has drawn more and more attention. However, traditional methods like mouse bioassays cannot meet the sharply increasing demand for drug and food toxicity assessment. In this study, a multifunctional cell-based impedance biosensor system is established for drug and toxin analysis, using a cell-based impedance biosensor (CIB) as the sensitive element. Cellular growth and beating experiments were carried out to verify the multifunctionality of the system. Four typical heart-related compounds including verapamil, bay K8644, chromanol 293B, and adriamycin were used for cardiotoxicity analysis function tests of the CIB system. Also, one typical marine diarrhetic toxin, okadaic acid (OA), was used for cytotoxicity analysis function tests of the CIB system. From the results, the CIB system can reflect the drug function and toxicity directly through the cell growth and beating status. According to the results, the multifunctional CIB system may provide a high-throughput and useful method for effective screening of cardiovascular drugs and marine toxins in vitro.

•A hippocampal neuronal network-based biosensor is designed and applied it in detecting 5-hydroxytryptamine (5-HT).•This biosensor is sensitive and specific in detecting 5-HT, which may provide promising approaches for neurotransmitter studies.5-hydroxytryptamine (5-HT) is an important neurotransmitter in regulating emotions and related behaviors in mammals. To detect and monitor the 5-HT, effective and convenient methods are demanded in investigation of neuronal network. In this study, hippocampal neuronal networks (HNNs) endogenously expressing 5-HT receptors were employed as sensing elements to build an in vitro neuronal network-based biosensor. The electrophysiological characteristics were analyzed in both neuron and network levels. The firing rates and amplitudes were derived from signal to determine the biosensor response characteristics. The experimental results demonstrate a dose-dependent inhibitory effect of 5-HT on hippocampal neuron activities, indicating the effectiveness of this hybrid biosensor in detecting 5-HT with a response range from 0.01 μmol/L to 10 μmol/L. In addition, the cross-correlation analysis of HNNs activities suggests 5-HT could weaken HNN connectivity reversibly, providing more specificity of this biosensor in detecting 5-HT. Moreover, 5-HT induced spatiotemporal firing pattern alterations could be monitored in neuron and network levels simultaneously by this hybrid biosensor in a convenient and direct way. With those merits, this neuronal network-based biosensor will be promising to be a valuable and utility platform for the study of neurotransmitter in vitro.

•We have developed a neuro-2a cell-based impedance biosensor to detect PSP toxins.•STX could be detected by this method with a detection limit as low as 0.1 nM.•This improved method has excellent specificity in marine toxins detection.Paralytic shellfish poisoning (PSP) toxins are well-known sodium channel-blocking marine toxins, which block the conduction of nerve impulses and lead to a series of neurological disorders symptoms. However, PSP toxins can inhibit the cytotoxicity effect of compounds (e.g., ouabain and veratridine). Under the treatment of ouabain and veratridine, neuroblastoma cell will swell and die gradually, since veratridine causes the persistent inflow of Na+ and ouabain inhibits the activity of Na+/K+-ATPases. Therefore, PSP toxins with antagonism effect can raise the chance of cell survival by blocking inflow of Na+. Based on the antagonism effect of PSP toxins, we designed an improved cell-based assay to detect PSP toxins using a neuroblastoma cell-based impedance biosensor. The results demonstrated that this biosensor showed high sensitivity and good specificity for saxitoxins detection. The detection limit of this biosensor was as low as 0.03 ng/ml, which was lower than previous reported cell-based assays and mouse bioassays. With the improvement of biosensor performance, the neuroblastoma cell-based impedance biosensor has great potential to be a universal PSP screening method.

•A portable cardiomyocyte-based potential biosensor is established to rapidly detect saxitoxin (STX) and brevetoxin (PbTX-2).•The potential biosensor can record high consistent and quite regular cardiomyocytes extracellular field potential (EFP) signals for 60 h.•The potential biosensor can detect 0.35 ng/ml STX and 1.55 ng/ml PbTX-2 within 5 min.Saxitoxin (STX) and brevetoxin (PbTX-2), which are produced by marine dinoflagellates, are highly-toxic marine toxins targeting separate sites of the α subunit of voltage-dependent sodium channels (VDSCs). In this work, a portable cardiomyocyte-based potential biosensor is designed for rapid detection of STX and PbTX-2. This potential biosensor is constructed by cardiomyocyte and microelectrode array (MEA) with a label-free and real-time wireless 8-channel recording system which can dynamically monitor the multisite electrical activity of cardiomyocyte network. The recording signal parameters, spike amplitude, firing rate and 50% of spike potential duration (SPD50) extracted from extracelluar field potential (EFP) signals of the potential biosensor is analyzed to quantitatively evaluate toxicological risk of STX and PbTX-2. Firing rate of biosensor signals presents high sensitivity to STX with the detection limit of 0.35 ng/ml within 5 min. SPD50 shows high sensitivity to PbTX-2 with the detection limit of 1.55 ng/ml within 5 min. Based on the multi-parameter analysis, cardiomyocyte-based potential biosensor will be a promising tool for rapid detection of these two toxins.

Herein, we present a novel miniaturized multisensor chip integrated with a nanoband electrode array (NEA) for lead and copper detection and a light addressable potentiometric sensor (LAPS) for pH sensing. By this means, pH information could be provided before electrochemical analysis to ensure high performance in heavy metal quantification due to the significant effects of solution acidity on electrochemical analyses. The fabrication processes of the multisensor chip are described in detail and the electrochemical behaviour of NEA was characterized using cyclic voltammetry in sulfuric acid and acetate buffer. For the detection of lead and copper qualitatively and quantitatively, square wave anodic stripping voltammetry (SWASV) was applied with the standard addition method. Deposition potential and deposition time were optimized to be −0.6 V and 120 s, respectively. NEA exhibited a sensitivity of 0.510 μA pbb−1 and 0.678 μA ppb−1 towards lead and copper, respectively, with high correlation coefficients. The repetitive and long-term experiments also demonstrated the good reproducibility and stability of NEA in heavy metal detection. Moreover, the silicon nitride modified LAPS showed a pH sensitivity of 56.49 mV pH−1 with a high correlation coefficient of 0.9999. The reproducibility of LAPS was also investigated and a deviation of less than 2 mV was obtained in both the samples. These results indicate that the miniaturized multisensor chip demonstrates good electrochemical performance in heavy metal and pH sensing.

With growing concern about human health, relevant drug and food toxicity has drawn more and more attention. However, traditional methods like mouse bioassays cannot meet the sharply increasing demand for drug and food toxicity assessment. In this study, a multifunctional cell-based impedance biosensor system is established for drug and toxin analysis, using a cell-based impedance biosensor (CIB) as the sensitive element. Cellular growth and beating experiments were carried out to verify the multifunctionality of the system. Four typical heart-related compounds including verapamil, bay K8644, chromanol 293B, and adriamycin were used for cardiotoxicity analysis function tests of the CIB system. Also, one typical marine diarrhetic toxin, okadaic acid (OA), was used for cytotoxicity analysis function tests of the CIB system. From the results, the CIB system can reflect the drug function and toxicity directly through the cell growth and beating status. According to the results, the multifunctional CIB system may provide a high-throughput and useful method for effective screening of cardiovascular drugs and marine toxins in vitro.