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Integrated Circuit Microfluidic Chips for Dielectric Manipulation

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Nội dung chi tiết: Integrated Circuit Microfluidic Chips for Dielectric Manipulation

Integrated Circuit Microfluidic Chips for Dielectric Manipulation

Integrated Circuit / Microfluidic Chips for Dielectric ManipulationThomas p. Hunt2’3, D. Issadore1, K.A. Brown1, Hakho Lee1-4, and R.M. Westervelt1-21

Integrated Circuit Microfluidic Chips for Dielectric Manipulation1School of Engineering & Applied Sciences. Harvard University, Cambridge MA 02138.2Dept of Physics, Harvard University, Cambridge, MA 02138.3Present a

ddress: Dept of Bioengineering, University of California, Berkeley. 94720.4Present address: Center for Molecular Imaging Research, Massachusetts Gener Integrated Circuit Microfluidic Chips for Dielectric Manipulation

al Hospital, Harvard Medical School, Charlestown, MA 02130.AbstractIn this chapter, we describe the development of Integrated-Circuit' Microfluidic ch

Integrated Circuit Microfluidic Chips for Dielectric Manipulation

ips that can move individual living cells and chemical droplets along programmable paths using dielectrophoresis (DEP). These hybrid chips combine the

Integrated Circuit / Microfluidic Chips for Dielectric ManipulationThomas p. Hunt2’3, D. Issadore1, K.A. Brown1, Hakho Lee1-4, and R.M. Westervelt1-21

Integrated Circuit Microfluidic Chips for Dielectric Manipulationectly on top of the IC - and they offer new opportunities for sensing, actuation, and control. IC'Microfhiidic chips can independently control the loc

ation of hundreds of dielectric objects, such as biological cells or chemical droplets, in the microfluidic chamber at the same time. The IC couples w Integrated Circuit Microfluidic Chips for Dielectric Manipulation

ith suspended objects by using spatially patterned, timedependent electromagnetic fields. The IC layout is similar to a computer display: it consists

Integrated Circuit Microfluidic Chips for Dielectric Manipulation

of a two-dimensional array of 128x256 metal ’pixels', each 11x11 pnr in size, controlled by a built-in SRAM memory. Each pixel can be energized by a r

Integrated Circuit / Microfluidic Chips for Dielectric ManipulationThomas p. Hunt2’3, D. Issadore1, K.A. Brown1, Hakho Lee1-4, and R.M. Westervelt1-21

Integrated Circuit Microfluidic Chips for Dielectric ManipulationUsing this IC/Microfluidic chip, we have moved yeast and mammalian cells along programmed paths at speeds up to 300 pm.'sec. Hundreds of cells can be

individually trapped and simultaneously positioned into controlled patterns. The chip can trap and move pL droplets of water in oil, split one droplet Integrated Circuit Microfluidic Chips for Dielectric Manipulation

into two, and mix two droplets into one, allowing one to conduct experiments with chemicals and individual cells, using tiny amounts of fluid. Our IC

Integrated Circuit Microfluidic Chips for Dielectric Manipulation

/Microfluidic chip provides a programmable platform that can individually control the motion of large numbers of cells and fluid droplets simultaneous

Integrated Circuit / Microfluidic Chips for Dielectric ManipulationThomas p. Hunt2’3, D. Issadore1, K.A. Brown1, Hakho Lee1-4, and R.M. Westervelt1-21

Integrated Circuit Microfluidic Chips for Dielectric Manipulation and cell sorting demand fast and efficient manipulation of increasingly large numbers of decreasingly small volumes of fluids. The burgeoning field o

f microfluidics has produced a library of miniaturized tools to interact with biological objects and sub-microliter fluid samples on the length scale Integrated Circuit Microfluidic Chips for Dielectric Manipulation

of single cells. Tools such as valves, pipes, and mixers have been fabricated in materials such as glass, silicon, and inexpensive polymer molds to co

Integrated Circuit Microfluidic Chips for Dielectric Manipulation

ntrol fluids on the micrometer scale (Whitesides et al., 2001, Slone el al., 2005, Tabeling el al., 2005). A micrograph of polymer microfluidic channe

Integrated Circuit / Microfluidic Chips for Dielectric ManipulationThomas p. Hunt2’3, D. Issadore1, K.A. Brown1, Hakho Lee1-4, and R.M. Westervelt1-21

Integrated Circuit Microfluidic Chips for Dielectric Manipulationniaturized tools that can be integrated into small, complex, and cheap laboratories-on-a-chip, is analagous to what was faced by the semiconductor ind

ustry' half of a century ago and which led to the integrated circuit (IC) (Throsen et al., 2002, Lee et al., 2007). Electronic circuits fifty years ag Integrated Circuit Microfluidic Chips for Dielectric Manipulation

o were built from discrete elements and could perform specific tasks. These simple circuits eventually gave way to integrated circuits and eventuallyi

Integrated Circuit Microfluidic Chips for Dielectric Manipulation

imicroprocessors that could be programmed to execute many different tasks and are now ubiquitously found as the brains of modem technology. An example

Integrated Circuit / Microfluidic Chips for Dielectric ManipulationThomas p. Hunt2’3, D. Issadore1, K.A. Brown1, Hakho Lee1-4, and R.M. Westervelt1-21

Integrated Circuit Microfluidic Chips for Dielectric Manipulationd handling elements will open up many possibilities for fluidic systems. MicTolluidic devices have been built for many specific biological experiments

; one impressive recent example is a fully integrated on-chip DNA sequencer (Blazcj et al., 2006). Pneumatically actuated programmable microfluidic sy Integrated Circuit Microfluidic Chips for Dielectric Manipulation

stems arc currently being developed to meet the demand for complex fluid manipulation, as is shown in Figure ib (Squires Ct al., 2005).Discrete electr

Integrated Circuit Microfluidic Chips for Dielectric Manipulation

onics has been combined with microfluidics to provide enhanced capabilities such as programmable fluid handling, chemical and biological sensing, cont

Integrated Circuit / Microfluidic Chips for Dielectric ManipulationThomas p. Hunt2’3, D. Issadore1, K.A. Brown1, Hakho Lee1-4, and R.M. Westervelt1-21

Integrated Circuit Microfluidic Chips for Dielectric Manipulationel al., 2007). Hybrid IO Microfluidic systems have been developed in which the fluidics are built directly on top of integrated circuits offering unpr

ecedented sensing and actuation (Figure Id).An integrated circuit with hundreds of millions of transistors connected by a complex network of wires can Integrated Circuit Microfluidic Chips for Dielectric Manipulation

be inexpensively mass-produced on a silicon chip. Devices on a chip are capable of detecting and producing electric and magnetic fields, heat, and li

Integrated Circuit Microfluidic Chips for Dielectric Manipulation

ght, providing a variety ol ways to probe and sense objects nearby. GHz switc hing speeds can be easily achieved. The steady miniaturization of circui

Integrated Circuit / Microfluidic Chips for Dielectric ManipulationThomas p. Hunt2’3, D. Issadore1, K.A. Brown1, Hakho Lee1-4, and R.M. Westervelt1-21

Integrated Circuit Microfluidic Chips for Dielectric Manipulation one billion transistors, made using a 45 nm process. To sense the spatial scale of devices on ỈC.S, consider that > 1000 transistors fit in the 10x10

pm' area beneath a single cell, or below a pLiiihttps://khothuvien.cori!droplet. It is remarkable that ICs with these characteristics can be inexpens Integrated Circuit Microfluidic Chips for Dielectric Manipulation

ively mass produced, at costs of a few dollars per chip.HuntLee, et disintegrated circuits interact with fluids and biological samples by generating a

Integrated Circuit Microfluidic Chips for Dielectric Manipulation

nd sensing electric and magnetic fields. Nano-particles (Green et al., 1997, Cohen et al., 2005), cells (Pohl et al., 1966, Manaresi et al., 2003), mo

Integrated Circuit / Microfluidic Chips for Dielectric ManipulationThomas p. Hunt2’3, D. Issadore1, K.A. Brown1, Hakho Lee1-4, and R.M. Westervelt1-21

Integrated Circuit Microfluidic Chips for Dielectric Manipulationo-patterned electric fields using dielectrophoresis (Pohl et al., 1966, Green et al., 1997, Manaresi el al., 2003, Hunt et al., 2008), electrophoresis

(Cohen et al., 2005), electro-osmosis (Cohen et al., 2005), and electro-wetting (Cho et al., 2005). Likewise, magnetic nanoparticles attached to biol Integrated Circuit Microfluidic Chips for Dielectric Manipulation

ogical samples have been trapped and moved (Lee et al., 2003), and sorted with magnetic fields (Inglis et al., 2004, Xia et al., 2006, Lee et al., 200

Integrated Circuit Microfluidic Chips for Dielectric Manipulation

7).In addition to moving and sorting objects, integrated circuits have been used to sense nanoparticles, cells, and fluids. One modality is to electri

Integrated Circuit / Microfluidic Chips for Dielectric ManipulationThomas p. Hunt2’3, D. Issadore1, K.A. Brown1, Hakho Lee1-4, and R.M. Westervelt1-21

Integrated Circuit Microfluidic Chips for Dielectric ManipulationWood, 2005) of biological fluids (Facer et al., 2001), nano-particles (Wood. 2005), and cells (Poloveya, 2001) has been demonstrated. In addition, ele

ctric fields can be used for recording and stimulating electrogenic cells (DeBusschere et al., 2001, Eversmann et al., 2003).Magnetic sensing has been Integrated Circuit Microfluidic Chips for Dielectric Manipulation

used to cany out nuclear magnetic resonance (NMR) measurements of fluids and biological objects. Systems for NMR spectroscopy have been miniaturized

Integrated Circuit Microfluidic Chips for Dielectric Manipulation

(Maguire et al., 2007) and a hand-held system for small-scale T2 relaxometry has been developed (Yong et al., 2008). Additionally, optical systems hav

Integrated Circuit / Microfluidic Chips for Dielectric ManipulationThomas p. Hunt2’3, D. Issadore1, K.A. Brown1, Hakho Lee1-4, and R.M. Westervelt1-21

Integrated Circuit Microfluidic Chips for Dielectric Manipulations et al., 2006), and nanopanicle sensing (Psaltis et al., 2006, Chin et al., 2007).IC/Microfluidic chips offer the possibility to control single suspe

nded cells and pL droplets of fluids: sensing and actuation can be tied together in a feedback loop to make smart chips for biomedical applications. M Integrated Circuit Microfluidic Chips for Dielectric Manipulation

oving a small object in a microfluidic chamber requires times ~ 1 msec or more. This allows a chip operating on a GHz clock to run many computations d

Integrated Circuit Microfluidic Chips for Dielectric Manipulation

uring each actuation cycle. IG Microfluidics chips can be made with areas (~ 1 cm2) large enough to sense and control the motion of hundreds of cells

Integrated Circuit / Microfluidic Chips for Dielectric ManipulationThomas p. Hunt2’3, D. Issadore1, K.A. Brown1, Hakho Lee1-4, and R.M. Westervelt1-21

Integrated Circuit Microfluidic Chips for Dielectric Manipulationnd droplets. Dielectrophoresis, the motion of a dielectric object caused by changes in electric field magnitude, provides a versatile manipulation sch

eme that is well suited to microfluidic systems. By using a spatially patterned electric field, one can apply a force to any object that has a dielect Integrated Circuit Microfluidic Chips for Dielectric Manipulation

ric constant different than the surrounding liquid with DEP. Most DEP systems rely on a small number of electrodes to perform a set task. Dielectropho

Integrated Circuit Microfluidic Chips for Dielectric Manipulation

resis has been used to move cells (Pohl and Crane, 1971), nanoparticles (Green and Morgan, 1997), viruses (Green et al., 1997), and single molecules (

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