Melinda G. Simon

A Laplace pressure based microfluidic trap for passive droplet trapping and controlled release.

Here, we present a microfluidic droplet trap that takes advantage of the net Laplace pressure force generated when a droplet is differentially constricted. Mathematical simulations were first used to understand the working range of the component; followed by finite element modeling using the CFD software package to further characterize the behavior of the system. Controlled release of the trapped droplets is also demonstrated through both a mechanical method and a chemical method that manipulates the total pressure exerted on the trapped droplet. The unique design of this trapping device also provides the capability for selection of a single droplet from a train, as well as droplet fusion.

Machine learning: A crucial tool for sensor design

Sensors have been widely used for disease diagnosis, environmental quality monitoring, food quality control, industrial process analysis and control, and other related fields. As a key tool for sensor data analysis, machine learning is becoming a core part of novel sensor design. Dividing a complete machine learning process into three steps: data pre-treatment, feature extraction and dimension reduction, and system modeling, this paper provides a review of the methods that are widely used for each step. For each method, the principles and the key issues that affect modeling results are discussed. After reviewing the potential problems in machine learning processes, this paper gives a summary of current algorithms in this field and provides some feasible directions for future studies.

Microfluidic Droplet Manipulations and Their Applications

“Droplet microfluidics” enables the manipulation of discrete fluid packets in the form of microdroplets that provide numerous benefits for conducting biological and chemical assays. Among these benefits are a large reduction in the volume of reagent required for assays, the size of sample required, and the size of the equipment itself. Such technology also enhances the speed of biological and chemical assays by reducing the volumes over which processes such as heating, diffusion, and convective mixing occur. Once the droplets are generated, carefully designed droplet operations allow for the multiplexing of a large number of droplets to enable large-scale complex biological and chemical assays. In this chapter, four major unit operations in droplets are discussed: droplet fusion, droplet fission, mixing in droplets, and droplet sorting. Combined, these operations allow for much complexity in executing chemical reactions and biological assays at the microscale. A broad overview of potential applications for such technology is provided throughout. While much research effort has been focused on the development of these individual devices, far fewer attempts to integrate these components have been undertaken. A review of many microfluidic unit operation devices is provided here, along with the advantages and disadvantages of each approach for various applications.

Increasing label-free stem cell sorting capacity to reach transplantation-scale throughput.

Dielectrophoresis (DEP) has proven an invaluable tool for the enrichment of populations of stem and progenitor cells owing to its ability to sort cells in a label-free manner and its biological safety. However, DEP separation devices have suffered from a low throughput preventing researchers from undertaking studies requiring large numbers of cells, such as needed for cell transplantation. We developed a microfluidic device designed for the enrichment of stem and progenitor cell populations that sorts cells at a rate of 150,000 cells/h, corresponding to an improvement in the throughput achieved with our previous device designs by over an order of magnitude. This advancement, coupled with data showing the DEP-sorted cells retain their enrichment and differentiation capacity when expanded in culture for periods of up to 2 weeks, provides sufficient throughput and cell numbers to enable a wider variety of experiments with enriched stem and progenitor cell populations. Furthermore, the sorting devices presented here provide ease of setup and operation, a simple fabrication process, and a low associated cost to use that makes them more amenable for use in common biological research laboratories. To our knowledge, this work represents the first to enrich stem cells and expand them in culture to generate transplantation-scale numbers of differentiation-competent cells using DEP.

Novel on-demand droplet generation for selective fluid sample extraction

A novel microfluidic device enabling selective generation of droplets and encapsulation of targets is presented. Unlike conventional methods, the presented mechanism generates droplets with unique selectivity by utilizing a K-junction design. The K-junction is a modified version of the classic T-junction with an added leg that serves as the exit channel for waste. The dispersed phase fluid enters from one diagonal of the K and exits the other diagonal while the continuous phase travels in the straight leg of the K. The intersection forms an interface that allows the dispersed phase to be controllably injected through actuation of an elastomer membrane located above the inlet channel near the interface. We have characterized two critical components in controlling the droplet size-membrane actuation pressure and timing as well as identified the region of fluid in which the droplet will be formed. This scheme will have applications in fluid sampling processes and selective encapsulation of materials. Selective encapsulation of a single cell from the dispersed phase fluid is demonstrated as an example of functionality of this design.

Instrumentation and Sensors for Human Breath Analysis

Exhaled breath contains a vast milieu of compounds, both volatile and non-volatile, that appear to correlate with physiological processes on-going in the body. These breath biomarkers hold enormous diagnostic potential when they are adequately measured and monitored. Thus, instrumentation geared towards breath analysis applications has expanded rapidly in the last decade, although challenges for future research still exist. This chapter briefly reviews the history of analytical instrumentation and breath biosensors that have been reported in the literature, and corresponding data analysis approaches that have been attempted to date.

3-D In-Bi-Sn Electrodes for Lab-on-PCB Cell Sorting

We present a microfluidic lab-on-printed circuit board (PCB) device containing alloy vertical electrodes for sorting microparticles using dielectrophoresis. The device consists of a hydrodynamic prefocuser and an electronic sorting region. Lining the two sidewalls of the electronic sorting region are regularly spaced rectangular metal electrodes reaching from the floor to the ceiling of the flow channel that bridge electric field lines laterally across the channel. The size and distribution of these vertical electrodes are arranged asymmetrically such that the resultant electric field forms sharp electric field gradients across the channel; specific geometries were optimized using finite element methods. Particles entering the device are initially focused on a single stream as they pass through the prefocuser. Subsequently, they are exposed to the lateral electric field gradient and separate into streams based on their size and dielectric properties. Validation was performed by dielectrophoretically separating live cells from dead cells. Importantly, the system presented can be readily integrated with various external sensors and actuators using commercially available components owing to the devices integration into a PCB.