Biological systems that are able to detect cancer cells and treat systemic diseases, e.g. Inflammatory Bowel Disease, have recently been synthetically designed using principles from electronic engineering. Both prokaryotic and eukaryotic cells have been engineered to mimic electronic systems using this interdisciplinary approach, resulting in devices such as toggle switches, oscillators and amplifiers that process molecules as information signals. An example of a synthetically engineered device proposed by the TSSG is a digital logic circuit that is created from bacteria illustrated in Fig. 1. The design involves developing a pill with compartments, and each compartment holds a population of bacteria that represents a logica gate. The communication between the gates is established through molecular communications. The computational study focuses on the quality performance and reliability analysis of the synthetic logic circuit as molecules are communicated in the circuits.
Figure 1 – Illustration of three engineered bacterial populations that execute Boolean operations. For this system, diffused molecules are used to communicate between the logic gates of the circuit.
In this research work, a compartmented microfluidic box is used to isolate three engineered bacterial populations, which can exchange molecules through a filtered wall and only allows molecules to pass and not the bacteria. The flow of molecules between the chambers A, B, and C enables the logic circuit to compute the incoming signals into the pill.
The reliability and the channel capacity of the circuit was investigated by evaluating the molecular signals and its diffusion process. The circuit’s quality was evaluated by comparing the ouput molecular signal, after the computing operation, with the expected values. From this comparison, the true positive of molecular concentration production above a certain threshold and true negative, when below the same threshold, were analysed and used to evaluate five metrics: accuracy_ratio, precision_ratio, recall_ratio, false negative_ratio and false positive_ratio. The channel capacity was evaluated using the information entropy of molecular signals that is communicated in the circuit.
Fig. 2 presents two results from the study. The quality analysis, depicted in Figure 2a, shows that as the output bit-1 ratios (number of true positives over the total samples) increases, the accuracy_ratio and false positive_ratio reduces. At the same time, the precision_ratio, recall_ratio and false negative_ratio do not show any significant variations. Figure 2b shows the system channel capacity when the circuit is subjected to delays between different signal inputs into the circuit in parallel to different molecular signal amplitudes. The result shows that the delay in the signals has a greater impact on the system, than variations in the molecular signal amplitudes.
Figure 2 – Example results of the quality and channel capacity analysis for the proposed synthetic circuit. (a) Quality metrics results for different output bit-1 ratios. (b) Channel capacity for different delays of input signals for the three gates with different input concentration difference (molecular signal amplitudes) values.
This research work demonstrates that the integration of synthetic biology and molecular communications can result in new types of molecular computing devices that has the potential to be used in future implantables for healthcare and animal monitoring applications.
Authors: Daniel P. Martins, Michael T. Barros, Sasitharan Balasubramaniam
Journal: IEEE Transactions on NanoBioscience (to appear, 2019)