Compact Empirical Model for Droplet Generation in a Lab-on-Chip Cytometry System

This study describes the construction of a droplet generation speed compact empirical mathematical model for a flow-focusing microfluidic droplet generator. The application case is a portable, low-cost flow cytometry system for microbiological applications, with water droplet sizes of 50-70 micrometer range and droplet generation rates of 500-1500 per second. In this study, we demonstrate that for the design of reliable microfluidic systems, the availability of an empirical model of droplet generation is a mandatory precondition that cannot be achieved by time-consuming simulations based on detailed physical models. When introducing the concept of a compact empirical model, we refer to a mathematical model that considers general theoretical estimates and describes experimental behavioral trends with a minimal set of easily measurable parameters. By interpreting the experimental results for different water- and oil-phase flow rates, we constructed a minimal 3-parameter droplet generation rate model for every fixed water flow rate by relying on submodels of the water droplet diameter and effective ellipticity. As a result, we obtained a compact model with an estimated 5-10% accuracy for the planned typical application modes. The main novelties of this study are the demonstration of the applicability of the linear approximation model for droplet diameter suppression by the oil flow rate, introduction of an effective ellipticity parameter to describe the droplet form transformation from a bullet-like shape to a spherical shape, and introduction of a machine learning correction function that could be used to fine-tune the model during the real-time operation of the system

Co-Design of Wireless Networked Control Systems: a Reliable and Resource-Efficient Approach

In this research, we provide a co-design strategy for WNCS that simultaneously optimizes network and control parameters. The goal is to optimize power use on the wireless communication layer by establishing a variable inter-packet gap (IPG) or by transforming the control strategy from reliable control to energy-efficient control with moderate reliability. Control performance is optimized for moderate to high packet loss using an RL-based technique that guarantees optimal resource allocation. The design of a multi-objective issue that takes into account both dependability and resource efficiency makes this possible. The developed approach is then applied to the multi-objective optimization problem. The suggested co-design RL-based control approach shows the ability to reduce transmission power by an average of 5% to 10% even when there are losses in the network. In addition, it effectively preserves or enhances control performance.</p

Integrated self-regulating resistive heating for isothermal nucleic acid amplification tests (NAAT) in Lab-on-a-Chip (LoC) devices

<div><p>Isothermal nucleic acid amplification tests (NAAT) in a Lab-on-a-Chip (LoC) format promise to bring high-accuracy, non-instrumented rapid tests to the point of care. Reliable rapid tests for infectious diseases allow for early diagnosis and treatment, which in turn enables better containment of potential outbreaks and fewer complications. A critical component to LoC NAATs is the heating element, as all NAAT protocols require incubation at elevated temperatures. We propose a cheap, integrated, self-regulating resistive heating solution that uses 2xAAA alkaline batteries as the power source, can maintain temperatures in the 60–63°C range for at least 25 minutes, and reaches the target range from room temperature in 5 minutes. 4 heating element samples with different electrical characteristics were evaluated in a thermal mock-up for a LoC NAAT device. An optimal heating element candidate was chosen based on temperature profiling. The optimal candidate was further evaluated by thermal modelling via finite element analysis of heat transfer and demonstrated suitable for isothermal nucleic acid amplification.</p></div

Optical Detection Methods for High-Throughput Fluorescent Droplet Microflow Cytometry

High-throughput microflow cytometry has become a focal point of research in recent years. In particular, droplet microflow cytometry (DMFC) enables the analysis of cells reacting to different stimuli in chemical isolation due to each droplet acting as an isolated microreactor. Furthermore, at high flow rates, the droplets allow massive parallelization, further increasing the throughput of droplets. However, this novel methodology poses unique challenges related to commonly used fluorometry and fluorescent microscopy techniques. We review the optical sensor technology and light sources applicable to DMFC, as well as analyze the challenges and advantages of each option, primarily focusing on electronics. An analysis of low-cost and/or sufficiently compact systems that can be incorporated into portable devices is also presented

Boundary conditions and initial parameter values for the model.

<p>Boundary conditions and initial parameter values for the model.</p

Material properties for the model.

<p>Material properties for the model.</p

Heating element sample performance in the tested Lab-on-a-Chip experimental setup.

<p>Although differences were minor, heating element BM117-83-B1 was the most suitable candidate from the tested samples, both with respect to steady-state temperature and rise times achieved during the test.</p

Design parameters for self-regulating PTC polymer heaters from Heatron Inc.

<p>Design parameters for self-regulating PTC polymer heaters from Heatron Inc.</p

Evaluation of the self-regulating resistive heating element with an on-chip isothermal nucleic acid amplification protocol.

<p>Two Lab-on-a-Chip prototypes with two reaction chambers were prepared along with reaction volumes including samples and master mix separately (A). After 30 minutes of incubation with the heating element, reaction volumes were extracted into Eppendorf tubes and lateral flow strips were added to detect amplicons. The experiment was repeated twice with two chips. Results indicated a successful amplification for all 8 reaction volumes (B). The result was confirmed by separately performing LAMP for a positive and negative control in Eppendorf tubes (C).</p

Comparison of the simulated temperature distribution to the thermal image of the physical prototype.

<p>Both simulated (A) and experimentally recorded (C) images are shown in steady state. Heating element BM117-83-B1 was selected as the candidate for comparison due to its favorable performance. Its temperature-dependent resistivity profile was fed into the model. In both the physical and simulated prototype, temperature probes were placed in the same spot (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0189968#pone.0189968.g001" target="_blank">Fig 1C</a>) and recorded steady-state temperatures compared. The model estimated recorded temperatures with less than 0.2°C absolute error.</p