Microfluidic Molecular Communications: Design, Theory, and Manufacture

Lead Research Organisation: King's College London
Department Name: Informatics

Abstract

Molecular communication (MC) provides a way for nano/microdevices to communicate information over distance via chemical signals in nanometer to micrometer scale environments. The successful realization of MC will allow its future main applications, including drug delivery and environmental monitoring. The main hindrance for the MC application stands in the lack of nano/micro-devices capable of processing the time-varying chemical concentration signals in the biochemical environment. One promising solution is to design and implement programmable digital and analog building blocks, as they are fundamental building blocks for the signal processing at MC transceivers. With two existing approaches in realizing these building blocks, namely, biological circuits and chemical circuits, synthesizing biological circuits faces challenges such as slow speed, unreliability, and non-scalability, which motivates us to design novel chemical circuits-based functions for rapid prototyping and testing communication systems.

Conventional chemical circuits designs are mainly based on chemical reaction networks (CRNs) to achieve various concentration transformation during the steady state from the input to the output with all chemical reactions occurring in same "point" location. This kind of design does not fit for the time-varying signals in communication system due to that the temporal information can be invisible to even state-of-the-art molecular sensors with high chemical specificity that respond only to the total amount of the signaling molecules. Thus, this project aims to design the chemical reaction-based microfluidic MC prototypes with time-varying chemical signal processing functionalities, including modulation and
demodulation, encoding and decoding, emission and detection. This also facilitates the microfluidic drug delivery prototype design and cancer cell on chip testing under time-varying drug concentration signal.

This project has the ambitious vision to develop novel time-varying chemical concentration signal processing methodology for microfluidic MC and microfluidic drug delivery. In the long run,
1) our microfluidic MC results will enable the implementation of MC functionality into nanoscale machines, by downsizing the proposed components through the utilization of nanomaterials with fluidic properties, and by translating the functional chemistry into biological circuit designs;
2) our microfluidic drug delivery results will revolutionize the conventional drug delivery testing approach by enabling ICT technologies for novel in-vitro microfluidics for drug delivery, allowing rapid measurement of therapeutic effect, toxicology, to reduce development costs and minimize the use of animal models.

Planned Impact

The MIMIC project is the UK's first innovative effort to realize the signal processing and communication capabilities of the microfluidic device via chemical reactions, to address its fundamental theoretical and experimental aspects of microfluidic molecular communication, and to exploit efficient in-vitro drug delivery on cancer cell on chip.

The general communication and detection of nano/micro-devices are important to achieve precision embedded sensing and actuation in a wide range of future applications, including environmental monitoring, and drug delivery. The economic potential of this idea is enormous, which we can estimate by looking at the related market for nano-medicine (such as precision drug delivery): studies estimate the present market size at $96.9 billion (2016), with a 14.1% per year growth (BCC Research Report). This project contributes to "Digital Signal Processing" and "Microsystems" EPSRC research areas, and also directly aligns to the EPSRC Healthcare Technologies Grand Challenges by developing the enabling ICT technologies for the novel in vitro microfluidics for drug delivery.

The immediate beneficiaries will be the telecommunication, microfluidics, and drug delivery industries, in particular, our industry partners, Elveflow, and Mediwise. We will exploit the economic impact of our microfluidic prototypes 1) for delivering drugs to cancer cell on chip in the conditions closest to the physiological conditions via working with Elveflow; 2) for intelligent insulin delivery, with potential integration with Mediwise's GlucoWise platform with blood glucose monitoring capability. The long-term benefits of molecular communication research, as a potential enabling technology for the nanoscale communication in 6G, will also be exploited with IEEE P1906.1.1 standard committee on nanoscale communication system and Wireless World Research Forum (WWRF).

From the academic impact perspective, our communication components design, analysis, and optimization based on chemical circuits and microfluidics contribute to the field of molecular communication; our chemical circuits analysis and design contributes to the field of chemistry and synthetic biology; our flow-based microfluidic analysis and design contributes to the field of microfluidics; and our microfluidic drug delivery prototype contributes to the field of drug delivery. In the long run, 1) our microfluidic MC results will enable the implementation of MC functionality into nanoscale machines, by downsizing the proposed components through the utilization of nanomaterials with fluidic properties, and by translating the functional chemistry into biological circuit designs; 2) our microfluidic drug delivery results will revolutionize the conventional drug delivery testing approach by enabling ICT technologies for novel in-vitro microfluidics for drug delivery, allowing rapid measurement of therapeutic effect, toxicology, to reduce development costs and minimize the use of animal models.

By bringing together academic experts from chemistry, microfluidics, drug delivery, and molecular communication, as well as industry practitioners in microfluidics and bioengineering, we are able to cross-fertilize academic research between disparate but important disciplines and accelerate the molecular communication industry.

Publications

10 25 50
 
Description The communication engineering community has never stopped on the road of pioneering innovative applications to shorten the time needed for communication and expand the space and place of human interactions. Although most of interactions employ electromagnetic phenomena for communication, it is insufficient to enable nanonetworks and bio/nano-applications, such as Internet-of-nano-things, environment monitoring, and drug delivery. An alternative approach that has received increasing attention within the communication community over the last decade is Molecular Communication (MC) which employs chemical molecules as the information carrier. Considering that electronic devices can hardly be miniaturized into micro/nanoscale, a great challenge in MC is how to process chemical concentration signals over the molecular domain, and a lack of pure chemical circuits with analog/digital signal processing capabilities prevents it from unleashing the potential of MC for applications in medicine, biology, or environmental science.

In this project, we designed, analyzed, simulated, and prototyped the first experimental MC platform for processing chemical concentration signals through chemical reactions instead of relying on the assistance of electronic or mechanical devices. In our approach, we encoded the information into the acidity of the solution and used acid-base reactions as well as a pH-sensitive dye to shape, threshold, amplify, and detect chemical signals. We show that careful calibration and fine-tuning of the chemical reactions and the microfluidic platform geometry can ensure reliable information transmission. To illustrate the far-reaching implications of our MC platform design, we
• provide an open approach and all the building instructions accompanying software development for microfluidic MC platforms,
• reveal the strong dependency of the chemical and microfluidic design on communication performance,
• show how the chemical-reaction-based microfluidic system can be evaluated and optimized from the communication engineering perspective.
Exploitation Route Our work is likely to find a broad interest even beyond the communication engineering and chemistry communities. Our design, combining the selection of specific chemical reactions and the fine-tuning of the microfluidic setup architecture to achieve signal processing, can be applied by microfluidic research groups to their own designs and expand their current capabilities. Moreover, the biocompatible feature of our MC platform, achieved by replacing electronic devices with chemical reactions for signal processing, can stimulate and inspire the research of multidisciplinary cell biologists, despite MC still being a fairly new research field. For example, the development of our platform will provide new routes to explore drug delivery and open new opportunities to understand the response of organisms to the administration of drugs.
Sectors Chemicals

Digital/Communication/Information Technologies (including Software)

Environment

Healthcare

Manufacturing

including Industrial Biotechology

Pharmaceuticals and Medical Biotechnology

URL https://www.youtube.com/watch?v=rzgGDwzSxzg
 
Description Our Nature Communications paper entitled "Real-time signal processing via chemical reactions for a microfluidic molecular communication system" was publicized as a KCL news, that has been picked up by one of the UK's largest pharmaceutical magazines - PharmaTimes: KCL molecular communication system to revolutionize drug delivery - PharmaTimes. This is a publication with a reasonable footprint in the UK pharmaceutical trade, which leads to a way to engage with a medical audience to push forward industry applications of the MIMIC platform.
First Year Of Impact 2023
Sector Pharmaceuticals and Medical Biotechnology
Impact Types Policy & public services

 
Title Real-time signal processing via chemical reactions for a microfluidic molecular communication system 
Description Signal processing over the molecular domain is critical for analysing, modifying, and synthesizing chemical signals in molecular communication systems. However, the lack of chemical signal processing blocks and the wide use of electronic devices to process electrical signals in existing molecular communication platforms can hardly meet the biocompatible, non-invasive, and size-miniaturized requirements of applications in various fields, e.g., medicine, biology, and environment sciences. To tackle this, here we design and construct a liquid-based microfluidic molecular communication platform for performing chemical concentration signal processing and digital signal transmission over distances. By specifically designing chemical reactions and microfluidic geometry, the transmitter of our platform is capable of shaping the emitted signals, and the receiver is able to threshold, amplify, and detect the chemical signals after propagation. By encoding bit information into the concentration of sodium hydroxide, we demonstrate that our platform can achieve molecular signal modulation and demodulation functionalities, and reliably transmit text messages over long distances. This platform is further optimised to maximise data rate while minimising communication error. The presented methodology for real-time chemical signal processing can enable the implementation of signal processing units in biological settings and then unleash its potential for interdisciplinary applications. This dataset provides all the relevant raw data for each figure both in the main manuscript and in the Supplementary Information. 
Type Of Material Database/Collection of data 
Year Produced 2023 
Provided To Others? Yes  
Impact The data are extracted from the flow meters via serial communication, and from the spectrometer using the python-seabreeze library, which can be used for analytical model building and machine learning research of this field 
URL https://zenodo.org/record/8422464
 
Title MolCommUI 
Description MolCommUI is a Python3 software running with the GUI framework PyQt5, allowing to control of platforms designed for typical Molecular Communication applications. MolCommUI integrates the following functions: 1) Timed and scheduled chemical injection (e.g., using syringe pumps); 2) Flow rate measurement and control via PID controller; 3) UV-Visible spectrometry measurement. The software is designed so the platform is fully automated. 
Type Of Technology Software 
Year Produced 2023 
Open Source License? Yes  
Impact To facilitate accurate and reproducible measurement of our microfluidic molecular communications (MIMIC) platform's performance, we have also developed a Python-based software with a graphical user interface (GUI) that entirely automates signal generation through multi-pump synchronisation and control, real-time chemical signal recording, and data visualization. During COVID, our researchers can remotely monitor, control, and automate the experiments of our MIMIC platform, without the need to access to the lab daily. 
URL https://www.nature.com/articles/s41467-023-42885-0
 
Description Invited Talk at First International Symposium on Molecular and Biological Communications 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact I gave an invited talk on "Internet of Bio-Nano Things" virtually at the First International Symposium on Molecular and Biological Communications, it publicized our recent publications generated from this project.
Year(s) Of Engagement Activity 2021
URL https://wibicom.in/schedule
 
Description Organized the Online Workshop on Molecular, Biological, and Multi-Scale Communications 2023 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact The molecular communications research team at King's College London organized the Workshop on Molecular, Biological, and Multi-Scale Communications (WMBMC) on Jan. 19th, 2023. The main objective of this event is to provide the research community with an opportunity to meet and share their latest research and vision in the field of molecular communications. The WMBMC is endorsed by the IEEE ComSoc Technical Committee on Molecular, Biological and Multi-Scale Communications (MBMC-TC). The WMBMC is a one-day virtual event and features 17 invited talks by international experts in the area of molecular communications. This workshop attracted more than 100 registrations and attendance, and inspired research discussions, collaborations, and engagements with professional and general audiences all over the world. All the talks are recorded and posted on my group's Youtube Channel for education and research purchases.
https://sites.google.com/view/wmbmc
Year(s) Of Engagement Activity 2023
URL https://www.youtube.com/@intelligentconnectivitylab
 
Description The presentation at IEEE ACM NANOCOM 2022 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact More than 50 academics, PhD students, and Postdocs attended this presentation and sparked research questions and discussions for future collaboration.
Year(s) Of Engagement Activity 2022
URL https://nanocom.acm.org/nanocom2022/sessions.php
 
Description The presentation at IEEE Globecom 2022 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact My team member presented the work "Microfluidic AND gate design for molecular communication" in IEEE Globecom 2022 in person to publicize our recent work generated from this project.
Year(s) Of Engagement Activity 2022