Microwave Dielectric Heating of Drops in Microfluidic Devices

We present a technique to locally and rapidly heat water drops in microfluidic devices with microwave dielectric heating. Water absorbs microwave power more efficiently than polymers, glass, and oils due to its permanent molecular dipole moment that has a large dielectric loss at GHz frequencies. The relevant heat capacity of the system is a single thermally isolated picoliter drop of water and this enables very fast thermal cycling. We demonstrate microwave dielectric heating in a microfluidic device that integrates a flow-focusing drop maker, drop splitters, and metal electrodes to locally deliver microwave power from an inexpensive, commercially available 3.0 GHz source and amplifier. The temperature of the drops is measured by observing the temperature dependent fluorescence intensity of cadmium selenide nanocrystals suspended in the water drops. We demonstrate characteristic heating times as short as 15 ms to steady-state temperatures as large as 30 degrees C above the base temperature of the microfluidic device. Many common biological and chemical applications require rapid and local control of temperature, such as PCR amplification of DNA, and can benefit from this new technique.Comment: 6 pages, 4 figure

High Voltage Dielectrophoretic and Magnetophoretic Hybrid Integrated Circuit / Microfluidic Chip

A hybrid integrated circuit (IC)/microfluidic chip is presented that independently and simultaneously traps and moves microscopic objects suspended in fluid using both electric and magnetic fields. This hybrid chip controls the location of dielectric objects, such as living cells and drops of fluid, on a 60 times 61 array of pixels that are 30 times 38 mum2 in size, each of which can be individually addressed with a 50-V peak-to-peak dc-to-10-MHz radio-frequency voltage. These high-voltage pixels produce electric fields above the chip's surface with a magnitude |oarrE| ap 1 V/ mum, resulting in strong dielectrophoresis (DEP) forces |oarrFDEP| ap 1 nN. Underneath the array of DEP pixels, there is a magnetic matrix that consists of two perpendicular sets of 60 metal wires running across the chip. Each wire can be sourced with 120 mA to trap and move magnetically susceptible objects using magnetophoresis. The DEP pixel array and magnetic matrix can be used simultaneously to apply forces to microscopic objects, such as living cells or lipid vesicles, that are tagged with magnetic nanoparticles. The capabilities of the hybrid IC/microfluidic chip demonstrated in this paper provide important building blocks for a platform for biological and chemical applications.Engineering and Applied Science

Integrated Circuit / Microfluidic Chips for Dielectric Manipulation

Engineering and Applied Science

Magnetic Nanoparticles and microNMR for Diagnostic Applications

Sensitive and quantitative measurements of clinically relevant protein biomarkers, pathogens and cells in biological samples would be invaluable for disease diagnosis, monitoring of malignancy, and for evaluating therapy efficacy. Biosensing strategies using magnetic nanoparticles (MNPs) have recently received considerable attention, since they offer unique advantages over traditional detection methods. Specifically, because biological samples have negligible magnetic background, MNPs can be used to obtain highly sensitive measurements in minimally processed samples. This review focuses on the use of MNPs for in vitro detection of cellular biomarkers based on nuclear magnetic resonance (NMR) effects. This detection platform, termed diagnostic magnetic resonance (DMR), exploits MNPs as proximity sensors to modulate the spin-spin relaxation time of water molecules surrounding the molecularly-targeted nanoparticles. With new developments such as more effective MNP biosensors, advanced conjugational strategies, and highly sensitive miniaturized NMR systems, the DMR detection capabilities have been considerably improved. These developments have also enabled parallel and rapid measurements from small sample volumes and on a wide range of targets, including whole cells, proteins, DNA/mRNA, metabolites, drugs, viruses and bacteria. The DMR platform thus makes a robust and easy-to-use sensor system with broad applications in biomedicine, as well as clinical utility in point-of-care settings

Toolbox for Exploring Modular Gene Regulation in Synthetic Biology Training

We report a toolbox for exploring the modular tuning of genetic circuits, which has been specifically optimized for widespread deployment in STEM environments through a combination of bacterial strain engineering and distributable hardware development. The transfer functions of 16 genetic switches, programmed to express a GFP reporter under the regulation of the (acyl-homoserine lactone) AHL-sensitive luxR transcriptional activator, can be parametrically tuned by adjusting high/low degrees of transcriptional, translational, and post-translational processing. Strains were optimized to facilitate daily large-scale preparation and reliable performance at room temperature in order to eliminate the need for temperature controlled apparatuses, which are both cost-limiting and space-constraining. The custom-designed, automated, and web-enabled fluorescence documentation system allows time-lapse imaging of AHL-induced GFP expression on bacterial plates with real-time remote data access, thereby requiring trainees to only be present for experimental setup. When coupled with mathematical models in agreement with empirical data, this toolbox expands the scalability and scope of reliable synthetic biology experiments for STEM training

Microwave dielectric heating of non-aqueous droplets in a microfluidic device for nanoparticle synthesis

We describe a microfluidic device with an integrated microwave heater specifically designed to dielectrically heat non-aqueous droplets using time-varying electrical fields with the frequency range between 700 and 900 MHz. The precise control of frequency, power, temperature and duration of the applied field opens up new vistas for experiments not attainable by conventional microwave heating. We use a non-contact temperature measurement system based on fluorescence to directly determine the temperature inside a single droplet. The maximum temperature achieved of the droplets is 50 °C in 15 ms which represents an increase of about 25 °C above the base temperature of the continuous phase. In addition we use an infrared camera to monitor the thermal characteristics of the device allowing us to ensure that heating is exclusively due to the dielectric heating and not due to other effects like non-dielectric losses due to electrode or contact imperfection. This is crucial for illustrating the potential of dielectric heating of benzyl alcohol droplets for the synthesis of metal oxides. We demonstrate the utility of this technology for metal oxide nanoparticle synthesis, achieving crystallization of tungsten oxide nanoparticles and remarkable microstructure, with a reaction time of 64 ms, a substantial improvement over conventional heating methods.Engineering and Applied SciencesPhysic

Point-of-Care Diagnostics on a Chip

The topic of this book is the development of automated and inexpensive tools that transfer medical tests from a specialized clinical laboratory directly to the point of care, using biochip technology. Immediate access to medically relevant biochemical information for doctors and nurses promises to revolutionize patient care and dramatically lower costs. The miniaturization and automation of medical tests are made possible by biochip technology, that integrates advances in integrated circuits, microelectromechanical systems (MEMS), microfluidics, and electronics. The target audience for this book includes engineering and biomedical researchers who would like to develop or apply biochip technology. They can use this book as a review of the field and as a guide for the development of novel biochip technology for point of care medicine. This book can also be used as a teaching tool for engineering and biomedical students, as as well as a reference for physicians and health professionals

Diagnostic technologies for circulating tumour cells and exosomes

Circulating tumour cells (CTCs) and exosomes are promising circulating biomarkers. They exist in easily accessible blood and carry large diversity of molecular information. As such, they can be easily and repeatedly obtained for minimally invasive cancer diagnosis and monitoring. Because of their intrinsic differences in counts, size and molecular contents, CTCs and exosomes pose unique sets of technical challenges for clinical translation–CTCs are rare whereas exosomes are small. Novel technologies are underway to overcome these specific challenges to fully harness the clinical potential of these circulating biomarkers. Herein, we will overview the characteristics of CTCs and exosomes as valuable circulating biomarkers and their associated technical challenges for clinical adaptation. Specifically, we will describe emerging technologies that have been developed to address these technical obstacles and the unique clinical opportunities enabled by technological innovations

Integrated Circuit / Microfluidic Chip for Programmable Cell and Droplet Manipulation with Dielectrophoresis

We present an integrated circuit/microfluidic chip that traps and moves individual living biological cells and chemical droplets along programmable paths using dielectrophoresis (DEP). Our chip combines the biocompatibility of microfluidics with the programmability and complexity of integrated circuits (ICs). The chip is capable of simultaneously and independently controlling the location of thousands of dielectric objects, such as cells and chemical droplets. The chip consists of an array of 128 × 256 pixels, 11 × 11 µm2 in size, controlled by built-in SRAM memory; each pixel can be energized by a radio frequency (RF) voltage of up to 5 Vpp. The IC was built in a commercial foundry and the microfluidic chamber was fabricated on its top surface at Harvard. Using this hybrid chip, we have moved yeast and mammalian cells through a microfluidic chamber at speeds up to 30 µm sec–1. Thousands of cells can be individually trapped and simultaneously positioned in controlled patterns. The chip can trap and move pL droplets of water in oil, split one droplet into two, and mix two droplets into one. Our IC/microfluidic chip provides a versatile platform to trap and move large numbers of cells and fluid droplets individually for lab-on-a-chip applications.Engineering and Applied Science