Deep Reinforcement Learning-Based Approach for Efficient and Reliable Droplet Routing on MEDA Biochips

The micro-electrode-dot-array (MEDA) architecture provides precise droplet control and real-time sensing in digital microfluidic biochips. Previous work has shown that trapped charge under microelectrodes (MCs) leads to droplets being stuck and failures in fluidic operations. A recent approach utilizes real-time sensing of MC health status, and attempts to avoid degraded electrodes during droplet routing. However, the problem with this solution is that the computational complexity is unacceptable for MEDA biochips of realistic size. Consequently, in this work, we introduce a deep reinforcement learning (DRL)-based approach to bypass degraded electrodes and enhance the reliability of routing. The DRL model utilizes the information of health sensing in real time to proactively reduce the likelihood of charge trapping and avoid using degraded MCs. Simulation results show that our approach provides effective routing strategies for COVID-19 testing protocols. We also validate our DRL-based approach using fabricated prototype biochips. Experimental results show that the developed DRL model completed the routing tasks using a fewer number of clock cycles and shorter total execution time, compared with a baseline routing method. Moreover, our DRL-based approach provides reliable routing strategies even in the presence of degraded electrodes. Our experimental results show that the proposed DRL-based routing is robust to occurrences of electrode faults, as well as increases the lifetime and usability of microfluidic biochips compared to existing strategies.

Label-free detection of SARS-CoV-2 neutralizing antibodies in human serum by Bloch surface waves on 1D photonic crystal biochips

We propose a rapid serologic test based on disposable nano-photonic biochips for SARS-CoV-2 related antibodies. The label-free sensograms showed that positive and negative human serum samples were discriminated, enabling real-time and fast label-free detection. © 2022 The Author (s)

Label-free detection of SARS-CoV-2 neutralizing antibodies in human serum by Bloch surface waves on 1D photonic crystal biochips

We propose a rapid serologic test based on disposable nano-photonic biochips for SARS-CoV-2 related antibodies. The label-free sensograms showed that positive and negative human serum samples were discriminated, enabling real-time and fast label-free detection. © 2022 The Author (s)

Biochip Systems for Intelligence and Integration

Disease is one of the major threats to human life and health, and historically there have been many cases which threatened human life due to infectious diseases. In almost all cases, specific triggers for the emergence of disease can be identified, so there is an urgent need for effective detection and identification of most diseases, including infectious diseases. Therefore, this article proposes biochip systems as a tool for disease detection and risk assessment, and explains why they are effective in detecting disease, in terms of their working mechanisms, advantages and disadvantages, specific application scenarios and future trends.

Application and development of molecular diagnostic techniques for detection infectious diseases

With the development of the concept of precision medicine, under the background of the new coronavirus pneumonia epidemic, the clinical diagnosis and treatment of infectious diseases has received more and more attention. The experimental diagnosis technology with molecular biology as the core is used as important means for the clinical laboratory diagnosis of infectious diseases. This lcind of technology is paid special attention. In recent years, advances in nanomaterials, applied chemistry, photophysics, and biosensing technologies have also ushered in revolutionary and creative developments in molecular diagnostic technology. This article reviews the application and development of the latest molecular diagnostic technologies, such as next-generation quantitative PCR technology and gene sequencing technology, isothermal amplification technology, biochip and biosensor technology in the clinical diagnosis of infectious diseases. © 2022 Chinese Medical Journals Publishing House Co.Ltd. All rights reserved.

Adaptive Droplet Routing for MEDA Biochips via Deep Reinforcement Learning

Digital microfluidic biochips (DMFBs) based on a micro-electrode-dot-array (MEDA) architecture provide fine-grained control and sensing of droplets in real-time. However, excessive actuation of microelectrodes in MEDA biochips can lead to charge trapping during bioassay execution, causing the failure of microelectrodes and erroneous bioassay outcomes. A recently proposed enhancement to MEDA allows run-time measurement of microelectrode health information, thereby enabling synthesis of adaptive routing strategies for droplets. However, existing synthesis solutions are computationally infeasible for large MEDA biochips that have been commercialized. In this paper, we propose a synthesis framework for adaptive droplet routing in MEDA biochips via deep reinforcement learning (DRL). The framework utilizes the real-time microelectrode health feedback to synthesize droplet routes that proactively minimize the likelihood of charge trapping. We show how the adaptive routing strategies can be synthesized using DRL. We implement the DRL agent, the MEDA simulation environment, and the bioassay scheduler using the OpenAI Gym environment. Our framework obtains adaptive routing policies efficiently for COVID-19 testing protocols on large arrays that reflect the sizes of commercial MEDA biochips available in the marketplace, significantly increasing probabilities of successful bioassay completion compared to existing methods. © 2022 EDAA.

Minimization of MEDA Biochip-Size in Droplet Routing

With the increasing demand for fast, accurate, and reliable biological sensor systems, miniaturized systems have been aimed at droplet-based sensor systems and have been promising. A micro-electrode dot array (MEDA) biochip, which is one kind of the miniaturized systems for biochemical protocols such as dispensing, dilutions, mixing, and so on, has become widespread due to enabling dynamical control of the droplets in microfluidic manipulations. In MEDA biochips, the electrowetting-on-dielectric (EWOD) technique stands out since it can actuate droplets with nano/picoliter volumes. Microelectrode cells on MEDA actuate multiple droplets simultaneously to route locations for the purpose of the biochemical operations. Taking advantage of the feature, droplets are often routed in parallel to achieve high-throughput outcomes. Regarding parallel manipulation of multiple droplets, however, the droplets are known to be initially placed at a distant position to avoid undesirable mixing. The droplets thus result in traveling a long way for a manipulation, and the required biochip size for routing is also enlarged. This paper proposes a routing method for droplets to reduce the biochip size on a MEDA biochip with the allowance of splitting during routing operations. We mathematically derive the routing problem, and the experiments demonstrate that our proposal can significantly reduce the biochip size by 70.8% on average, compared to the state-of-the-art method.

Securing Biochemical Samples Using Molecular Barcoding on Digital Microfluidic Biochips*

Microfluidic biochips are being adopted today in point-of-care diagnostics, e.g., COVID-19 testing;therefore, it is critical to ensure integrity of bio-sample before bioassays are run on-chip. A security technique called molecular barcoding was recently proposed to thwart sample-forgery attacks in DNA forensics. Molecular barcoding refers to addition of unique DNA molecules in bio-samples, and the sequence of the added DNA sample serves as a distinct 'barcode' for the sample. The existence of the added molecule can be validated using polymerase chain reaction (PCR) and gel electrophoresis. However, this security solution has several limitations: (1) the lack of robustness of the barcode molecules when they are added to other genomic DNA (e.g., samples collected for diagnostics);(2) the need for special bulk instrumentation for validation;(3) the need for human intervention during the overall process. To overcome the limitations, we design a set of robust molecular barcodes that can be validated using both traditional polymerase chain reaction and loop mediated isothermal amplification (LAMP). The validation using LAMP can be executed on a small-in-size and portable digital microfluidic biochip (DMFB). Our LAMP workflow includes a color-changing visual indicator for simple, rapid identification of the barcode existence in solutions. We first demonstrate the proposed security workflow using benchtop techniques. Next, we fabricate a printed circuit board (PCB)-based DMFB with heaters and demonstrate, for the first time, the LAMP assay on a DMFB. © 2021 IEEE.