Utilizing Deep Learning Algorithms for Signal Processing in Electrochemical Biosensors: From Data Augmentation to Detection and Quantification of Chemicals of Interest.

Nanomaterial-based aptasensors serve as useful instruments for detecting small biological entities. This work utilizes data gathered from three electrochemical aptamer-based sensors varying in receptors, analytes of interest, and lengths of signals. Our ultimate objective was the automatic detection and quantification of target analytes from a segment of the signal recorded by these sensors. Initially, we proposed a data augmentation method using conditional variational autoencoders to address data scarcity. Secondly, we employed recurrent-based networks for signal extrapolation, ensuring uniform signal lengths. In the third step, we developed seven deep learning classification models (GRU, unidirectional LSTM (ULSTM), bidirectional LSTM (BLSTM), ConvGRU, ConvULSTM, ConvBLSTM, and CNN) to identify and quantify specific analyte concentrations for six distinct classes, ranging from the absence of analyte to 10 µM. Finally, the second classification model was created to distinguish between abnormal and normal data segments, detect the presence or absence of analytes in the sample, and, if detected, identify the specific analyte and quantify its concentration. Evaluating the time series forecasting showed that the GRU-based network outperformed two other ULSTM and BLSTM networks. Regarding classification models, it turned out signal extrapolation was not effective in improving the classification performance. Comparing the role of the network architectures in classification performance, the result showed that hybrid networks, including both convolutional and recurrent layers and CNN networks, achieved 82% to 99% accuracy across all three datasets. Utilizing short-term Fourier transform (STFT) as the preprocessing technique improved the performance of all datasets with accuracies from 84% to 99%. These findings underscore the effectiveness of suitable data preprocessing methods in enhancing neural network performance, enabling automatic analyte identification and quantification from electrochemical aptasensor signals.

Anomaly Detection for Sensor Signals Utilizing Deep Learning Autoencoder-Based Neural Networks.

Anomaly detection is a significant task in sensors' signal processing since interpreting an abnormal signal can lead to making a high-risk decision in terms of sensors' applications. Deep learning algorithms are effective tools for anomaly detection due to their capability to address imbalanced datasets. In this study, we took a semi-supervised learning approach, utilizing normal data for training the deep learning neural networks, in order to address the diverse and unknown features of anomalies. We developed autoencoder-based prediction models to automatically detect anomalous data recorded by three electrochemical aptasensors, with variations in the signals' lengths for particular concentrations, analytes, and bioreceptors. Prediction models employed autoencoder networks and the kernel density estimation (KDE) method for finding the threshold to detect anomalies. Moreover, the autoencoder networks were vanilla, unidirectional long short-term memory (ULSTM), and bidirectional LSTM (BLSTM) autoencoders for the training stage of the prediction models. However, the decision-making was based on the result of these three networks and the integration of vanilla and LSTM networks' results. The accuracy as a performance metric of anomaly prediction models showed that the performance of vanilla and integrated models were comparable, while the LSTM-based autoencoder models showed the least accuracy. Considering the integrated model of ULSTM and vanilla autoencoder, the accuracy for the dataset with the lengthier signals was approximately 80%, while it was 65% and 40% for the other datasets. The lowest accuracy belonged to the dataset with the least normal data in its dataset. These results demonstrate that the proposed vanilla and integrated models can automatically detect abnormal data when there is sufficient normal data for training the models.

Predicting Analyte Concentrations from Electrochemical Aptasensor Signals Using LSTM Recurrent Networks.

Nanomaterial-based aptasensors are useful devices capable of detecting small biological species. Determining suitable signal processing methods can improve the identification and quantification of target analytes detected by the biosensor and consequently improve the biosensor's performance. In this work, we propose a data augmentation method to overcome the insufficient amount of available original data and long short-term memory (LSTM) to automatically predict the analyte concentration from part of a signal registered by three electrochemical aptasensors, with differences in bioreceptors, analytes, and the signals' lengths for specific concentrations. To find the optimal network, we altered the following variables: the LSTM layer structure (unidirectional LSTM (LSTM) and bidirectional LSTM (BLSTM)), optimizers (Adam, RMSPROP, SGDM), number of hidden units, and amount of augmented data. Then, the evaluation of the networks revealed that the highest original data accuracy increased from 50% to 92% by exploiting the data augmentation method. In addition, the SGDM optimizer showed a lower performance prediction than that of the ADAM and RMSPROP algorithms, and the number of hidden units was ineffective in improving the networks' performances. Moreover, the BLSTM nets showed more accurate predictions than those of the ULSTM nets on lengthier signals. These results demonstrate that this method can automatically detect the analyte concentration from the sensor signals.

Comparison of Duplex and Quadruplex Folding Structure Adenosine Aptamers for Carbon Nanotube Field Effect Transistor Aptasensors.

Carbon nanotube field effect transistor (CNT FET) aptasensors have been investigated for the detection of adenosine using two different aptamer sequences, a 35-mer and a 27-mer. We found limits of detection for adenosine of 100 pM and 320 nM for the 35-mer and 27-mer aptamers, with dissociation constants of 1.2 nM and 160 nM, respectively. Upon analyte recognition the 35-mer adenosine aptamer adopts a compact G-quadruplex structure while the 27-mer adenosine aptamer changes to a folded duplex. Using the CNT FET aptasensor platform adenosine could be detected with high sensitivity over the range of 100 pM to 10 µM, highlighting the suitability of the CNT FET aptasensor platform for high performance adenosine detection. The aptamer restructuring format is critical for high sensitivity with the G-quadraplex aptasensor having a 130-fold smaller dissociation constant than the duplex forming aptasensor.