A Molecular Communication Perspective on Synchronization of Coupled Microfluidic-Spectroscopy.

A challenge for real-time monitoring of biochemical processes, such as cells, is detection of biologically relevant molecules. This is due to the fact that spectroscopy methods for detection may perturb the cellular environment. One approach to overcome this problem is coupled microfluidic-spectroscopy, where a microfluidic output channel is introduced in order to observe biologically relevant molecules. This approach allows for non-passive spectroscopy methods, such as mass spectrometry, to identify the structure of molecules released by the cell. Due to the non-negligible length of the microfluidic channel, when a sequence of stimuli are applied to a cell it is not straightforward to determine which spectroscopy samples correspond to a given stimulus. In this paper, we propose a solution to this problem by taking a molecular communication (MC) perspective on the coupled microfluidic-spectroscopy system. In particular, assignment of samples to a stimulus is viewed as a synchronization problem. We develop two new algorithms for synchronization in this context and carry out a detailed theoretical and numerical study of their performance. Our results show improvements over maximum-likelihood synchronization algorithms in terms of detection performance when there are uncertainties in the composition of the microfluidic channel.

Off-Chip-Controlled Droplet-on-Demand Method for Precise Sample Handling.

We present a simple, stable, and highly reproducible off-chip-controlled method for generating droplets-on-demand. To induce the droplet generation, externally pre-programmed positive pressure pulses are applied to the dispersed phase input while the continuous phase channel remains at constant input pressure. By controlling solely one fluid phase, the method allows for connecting multiple independent dispersed-phase channels to a single continuous channel. Experimental results show that the method allows for a droplet generation frequency of 33 Hz and a high reproducibility of droplets with standard deviations less than 5% of the mean value. Moreover, utilization of the off-chip-controlled method results in the simplicity in chip design and allows rapid (∼5 min) and cost-efficient (0.5 USD) prototyping of the device.

Simulation before fabrication: a case study on the utilization of simulators for the design of droplet microfluidic networks.

The functional performance of passively operated droplet microfluidics is sensitive with respect to the dimensions of the channel network, the fabrication precision as well as the applied pressure because the entire network is coupled together. Especially, the local and global hydrodynamic resistance changes caused by droplets make the task to develop a robust microfluidic design challenging as plenty of interdependencies which all affect the intended behavior have to be considered by the designer. After the design, its functionality is usually validated by fabricating a prototype and testing it with physical experiments. In case that the functionality is not implemented as desired, the designer has to go back, revise the design, and repeat the fabrication as well as experiments. This current design process based on multiple iterations of refining and testing the design produces high costs (financially as well as in terms of time). In this work, we show how a significant amount of those costs can be avoided when applying simulation before fabrication. To this end, we demonstrate how simulations on the 1D circuit analysis model can help in the design process by means of a case study. Therefore, we compare the design process with and without using simulation. As a case study, we use a microfluidic network which is capable of trapping and merging droplets with different content on demand. The case study demonstrates how simulation can help to validate the derived design by considering all local and global hydrodynamic resistance changes. Moreover, the simulations even allow further exploration of different designs which have not been considered before due to the high costs.

Bacterial Relay for Energy-Efficient Molecular Communications.

In multi-cellular organisms, molecular signaling spans multiple distance scales and is essential to tissue structure and functionality. Molecular communications is increasingly researched and developed as a key subsystem in the Internet-of-Nano-Things paradigm. While short range microscopic diffusion communications is well understood, longer range channels can be inefficient and unreliable. Static and mobile relays have been proposed in both conventional wireless systems and molecular communication contexts. In this paper, our main contribution is to analyze the information delivery energy efficiency of bacteria mobile relays. We discover that these mobile relays offer superior energy efficiency compared with pure diffusion information transfer over long diffusion distances. This paper has widespread implications ranging from understanding biological processes to designing new efficient synthetic biology communication systems.