Eric P. Y. Chiou

Floating electrode optoelectronic tweezers: Light-driven dielectrophoretic droplet manipulation in electrically insulating oil medium

We report an optical actuation mechanism, floating electrode optoelectronic tweezers (FEOET). FEOET enables light-driven transport of aqueous droplets immersed in electrically insulating oil on a featureless photoconductive glass layer with direct optical images. We demonstrate that a 681 mum de-ionized water droplet immersed in corn oil medium is actuated by a 3.21 muW laser beam with an average intensity as low as 4.08 muWmm(2) at a maximum speed of 85.1 mums on a FEOET device. FEOET provides a promising platform for massively parallel droplet manipulation with optical images on low cost, silicon-coated glass. The FEOET device structure, fabrication, working principle, numerical simulations, and operational results are presented in this letter.

Magnetic nanowire-enhanced optomagnetic tweezers

We report an optomagnetic tweezers technique that utilizes the highly localized magnetic field gradients induced near the tip of a magnetic nanowire to provide strong trapping forces on magnetic nanoparticles with high spatial resolution. Integral to our approach is a method to trap, translate, and rotate a single magnetic nanowire in three dimensions. Our simulation predicts that forces in the range of 100 pN can be generated on 200 nm magnetic particles within 0.2 μm from a 200 nm diameter nickel nanowire. Such forces are relevant in many biological processes, suggesting that this approach will be of value in biophysical studies.

3D pulsed laser triggered high speed microfluidic fluorescence activated cell sorter

We report a high speed microfluidic fluorescence activated cell sorter (μFACS) capable of sorting at a throughput of 3000 beads/sec and 560 cells/sec with >90% sample purity and 90% cell viability after sorting. The sorting mechanism is realized by exciting dynamic vapor bubbles with focused laser pulses in a microfluidic PDMS channel. The explosive bubble expansion generates fast fluid flows which are directed into a neighboring sample channel to switch the particle of interest into the collection channel. This ultrafast laser triggered switching mechanism has the potential to advance the sorting speed of the state-of-the-art μFACS.

Pulsed laser triggered high speed fluorescence activated microfluidic switch

We report a high speed fluorescence activated microfluidic switch capable of achieving a switching time of 50 µsec with a detection efficiency of 86.6% and a switching efficiency of 86.5% at a particle flow speed of ∼0.7 m/s. The switching mechanism is realized by exciting dynamic vapor bubbles with focused laser pulses in a microfluidic PDMS channel. The explosive bubble expansion generates fast fluid flows which are directed into a neighboring particle channel to switch the particle flow. Fluorescence activated switching of 10 micron polystyrene microspheres in a Y channel has been demonstrated. This ultrafast laser triggered switching mechanism has the potential to advance the sorting speed of the state-of-the-art microscale fluorescent activated cell sorting devices.

Optofluidics for Lab-on-a-Chip

1Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, CA, USA 2Department of Electrical Engineering, University of Hawaii at Manoa, Honolulu, HI, USA 3National Key Laboratory of Science and Technology on Micro/Nano Fabrication, Institute of Microelectronics, Peking University, Beijing, China 4Birck Nanotechnology Center, Purdue University, West Lafayette, IN, USA

Photothermal nanoblade delivers super-sized cargo into living cells

Tools and approaches that enable biologists to deliver extracellular materials into living cells are desired for numerous biological and biomedical research applications. Current physical methods use electric currents, light, or sound to create temporary pores in the cell membrane. However, these methods limit the size of the cargo that can be delivered. This limitation arises from the slow diffusion speed of large objects and their inability to cross transiently opened membrane pores in these approaches. Direct microinjection eliminates the slow diffusion issue by providing active pressure-driven delivery of cargo into a cell through a sharp glass pipette tip. However, to avoid severe cellular trauma and maintain cell viability, the size of the pipette tip usually must be kept below 200nm. During delivery, this small pipette nanochannel may clog near the tip. The method cannot be used to deliver cargo larger than the pipette tip’s inner diameter, such as organelles (e.g., peroxisomes, mitochondria, nuclei), beads, or intracellular pathogens (e.g., bacteria). In addition, some encapsulation approaches, such as use of lipofectamine to enclose cargo in liposomes for delivery, can result in large cargo becoming trapped or degraded in endosomes or endolysosomes. Recently, we demonstrated a new approach called a photothermal nanoblade, which can deliver cargo up to 2–3 microns in size.1, 2 The nanoblade utilizes an ultrahigh-speed, light-triggered cavitation bubble patterned by a metallic nanostructure to disrupt mammalian cell membranes and enable large cargo delivery (see Figure 1). To create the nanoblade, we coat the outer tip of a glass micropipette with a metallic thin film (approximately 100nm thick). Laser pulsing rapidly heats the nanoblade and triggers formation of a cavitation bubble that can Figure 1. High-speed membrane puncture mechanism using metallic nanostructure-guided cavitation to deliver small molecules and micron-sized cargo into somatic cells. Upon excitation by a nanosecond laser pulse, the titanium (Ti) blade heats up rapidly, producing an explosive cavitation bubble that expands and collapses in 200nsec, which locally disrupts the contacting cell membrane (three panels at right). Pressure-driven fluid flow injects the microcapillary contents into the cell in synchrony with the membrane disruption. SiO2: Silicon dioxide.

Advancements in Biomedical Micro/Nano Tools and Technology

Although both microtechnology and nanotechnology deal with small-length scales, their methodologies and even governing physics often differ from one another. Microtechnology was originally derived from top-down approaches for manufacturing of microelectronics, whereas its nanoscale counterpart is closely related to bottom-up synthetic chemistry as well as high-resolution microscopy such as the scanning electron microscope and the scanning tunneling microscope. Nevertheless, they complement each other, offering a valuable set of tools for exploring small yet intriguing worlds, which our bare eyes cannot observe. The combination of microand nanoscience and engineering is extremely relevant to biomedical science and applications because key building blocks of the biological systems fall into microand nanoscales: from small tissues (>100 μm), to single cells (~10 μm), to organelles (100 nm–1 μm), and to proteins, nucleic acids, and other macromolecules (1–100 nm). DNA and protein sensors and microarrays, microfluidic circuits for biochemical sample preparation, and drug delivery carriers are some early examples of microtechnology and nanotechnology applied to biomedical targets, here collectively called biomedical micro/nanotechnology. Sophistication and functionality of such devices and tools have improved significantly over the past few decades. Some emerging trends in the field include active, rather than passive, devices that can directly or indirectly manipulate biological objects, high-throughput systems, integration of multiple micro and nano components into automated systems, and applications for stem cells and tissue engineering. Such continued progress will lead to improvement over existing experimental techniques and medical procedures with enhanced accuracy and efficacy at lower costs. In this JALA special issue on Advancements in Biomedical Micro/Nano Tools and Technology, we are excited to introduce an excellent collection of articles that contribute to the development of this field. Because of an overwhelming number of impressive articles, we present them in two consecutive issues (this December 2013 issue and the February 2014 issue). A total of 21 articles are grouped based on their focus. In this first/December issue (volume 18, issue 6), articles present micro/nano platforms and core tools to investigate mammalian cell cultures. Opened by an extensive review article by Young1 on microfluidic platforms for studying angiogenesis, a total of 10 articles cover reviews of the latest microscale tools and technologies for in vitro cell culture and analysis2–6 and original research on development of new automated cell culture platforms and cell patterning and assembly techniques.7–10 In the February 2014 issue (volume 19, issue 1), we will publish an exciting collection of articles, particularly in tools and technology associated with measurement, analyses, and delivery. Two comprehensive reviews, one by Meacham et al. and the other by Pereira et al., on delivery technology at different length scales, will open this issue.11,12 We will also showcase original research on pathogen detection methods,13,14 intracellular delivery,15 electrical impedance characterization of porated cells,16 isolation and sorting methods based on multiple external force interactions,17,18 and development and characterization of new measurement materials and methods.19–21 We hope you enjoy the work of our colleagues in these two special issues. We sincerely thank them for their willingness to share their achievements with us all, and we look forward to reading more from them in coming years.

Light-Driven Microfluidic Platforms for Droplet-Based Biochemical Analysis

We report on two light-induced droplet actuation mechanisms, floating electrode optoelectronic tweezers (FEOET) and lateral field optoelectrowetting (LOEW), for manipulating aqueous droplets immersed in oil on a featureless photoconductive surface with an open chamber configuration. Droplet functions including transporting, merging, mixing, and splitting, and multi-droplet manipulation have been accomplished. Droplet manipulation in FEOET is based on light-induced dielectrophoretic forces in an electrically insulating medium such as oil. It has been shown that oilimmersed aqueous droplets can be actuated by a light beam with an intensity as low as 400 μW/cm2 in FEOET. However, due to the weak force generated by the DEP-based droplet actuation, the droplet moving speed is limited to hundreds of μm/s and performing other droplet manipulation functions such as splitting and injection is challenging on FEOET. On the other hand, LOEW-based droplet actuation is realized by modulating the interfacial surface tension of a droplet on a hydrophobic surface through a light-induced electrowetting effect. Since surface tension provides large forces than DEP on a droplet with a diameter from mm to hundreds of μm, LOEW allows transporting droplets at a speed in the range of cm/s and performing droplet-based functions such as splitting and injection. The open chamber configuration of these platforms provides flexibility in integration with other microfluidic components such as external reservoirs and tubing for broad chemical and biochemical applications.

Dynamic magnetic manipulation using electric field addressed ferrofluidic droplets

We present a novel magnetic manipulation mechanism capable of producing two-dimensional, dynamic magnetic trapping using electric field addressed free-suspending ferrofluidic droplets. This is realized by coupling a permanent magnet with a ferrofluidic droplet that induces a highly non-uniform magnetic field for manipulating other magnetic particles. By implementing an electrode design, we use electrostatic force to drive droplet movement, and in turn, other magnetic particles. Furthermore, by tilting the magnetic field, the position of a magnetic trap can be continuously tuned in a radial fashion. Experimentally, we have successfully demonstrated the trapping and transport of 1.05 mum magnetic beads as well as other ferrofluidic droplets.