HOT: label-free plasmonic microarray for high-throughput protein screening

Microarrays offer the opportunity for the high-throughput study of protein-protein interactions that may uncover drug targets and provide early detection of various diseases. Most current technologies rely on fluorescent labelling of proteins, but this is costly, time-consuming and can be inaccurate due to steric interference, quenching and photo-bleaching.

Hatice Altug, Boston University, and colleagues from MIT have now found a way to accomplish label free detection by using a dual-colour filter method to image large scale plasmonic nanohole arrays.  Their high-density detection platform has over 1 million sensors and has reliably demonstrated massively multiplexed detection of antibody bindings with reduced image acquisition time.

Download the paper to read how they did it, it’s free to access for the next 4 weeks:

Large-scale plasmonic microarrays for label-free high-throughput screening
Tsung-Yao Chang, Min Huang, Ahmet Ali Yanik, Hsin-Yu Tsai, Peng Shi, Serap Aksu, Mehmet Fatih Yanik and Hatice Altug
Lab Chip, 2011, Advance Article
DOI: 10.1039/C1LC20475K

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Corn microchips

US scientists have made microfluidic devices from a corn by-product, which makes them biodegradable and environmentally friendly.

Left: macro images of zein-glass and zein-zein microfluidic devices. The inset shows a colourant-filled zein-glass microfluidic device with tubings. Right: serpentine channels for mixing two different chemical fluids

Gang Logan Liu and colleagues at the University of Illinois Urbana-Champaign, have demonstrated that by using lithography and solvent or vapour deposition bonding, thin films of zein (a protein extracted from corn by-products) can be used to construct microfluidic channels, grids and wells as a green alternative to the plastic materials currently in use.

The group tested their zein microfluidic devices using several types of fluid, including fluorescent dyes and solutions of microbeads. They found that the devices did not leak and the channels could easily be viewed through a microscope. They also extended their work to produce a concentration gradient generator, mixing dye and solvent within serpentine channels to create several different concentration mixtures.

Liu anticipates being able to use the simple bonding of the zein films to make multilayer microfluidic devices in the future.

Interested? Read Tamsin Phillips’ full Chemistry World article here or download the Lab on a Chip paper:

Green microfluidic devices made of corn proteins
Jarupat Luecha, Austin Hsiao, Serena Brodsky, Gang Logan Liu and Jozef L. Kokini
Lab Chip, 2011, Advance Article
DOI: 10.1039/C1LC20726A

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Making nerve pathways in chips for brain studies

The study of brain development and degeneration is hindered by a lack of physiologically realistic models. French scientists have now developed a way to reconstruct neuronal networks in a microfluidic system to more closely mimic the directional neuronal pathways found in the brain.

Current experimental brain models include neuronal cell cultures and whole animal models; however, the former lack the complex architecture found in vivo, and the latter restrict studies at the cellular level. Aiming to bridge the gap between these models, Jean-Louis Viovy of the Curie Institute, Paris, and coworkers have developed a microfluidic device that allows for the growth of oriented and functional synaptic connections in vitro.

The device consists of two cell culture chambers connected by microchannels, through which axons – nerve fibres that conduct impulses away from the body of the nerve cell – can penetrate to form neuronal networks. In previous setups, replication of the unidirectional networks found in vivo could not be achieved since axons were sent from each chamber to the one opposite, travelling in both directions across the microchannel.

Inspired by the observation that axons can be mechanically constrained, the team modified the device to include asymmetric, funnel-shaped microchannels, termed ‘axon diodes’, to allow axons to grow from only one chamber to the other and not the opposite way. The concept was verified by experiments with mouse cortical neurons, in which the axon projection was 97 per cent selective for the ‘correct’ direction.

Neuronal networks have been grown in microfluidic chambers to replicate neural pathways in the brain

Next, by seeding cortical neurons (from the outer part of the brain) on the emitting side of the device and striatal neurons (from the inner part of the brain) on the receiving side, the team demonstrated the reconstruction of an active neuronal pathway involving two different neuronal subtypes. Furthermore, these networks were routinely maintained for three weeks in vitro, which would allow for both short and long-term experimentation.

‘I was struck by the simplicity of the system, it is beautiful,’ remarks Bonnie Firestein, an expert in cellular neurobiology from Rutgers University, New Jersey, US. ‘It is very easy to make and to use, and allows the recreation of what happens in vivo in an in vitro system.’

Such a device has many potential applications in neurobiological research. An initial motivation for this work was the requirement of a model to study the progression of neuronal damage in degenerative diseases such as Alzheimer’s. Additionally, Viovy believes the system is also an important platform for research into brain development and cognitive science. ‘How neurons communicate regarding information transmission is also an area in which we currently lack a model of the kind we have proposed here,’ he says. The team are currently working on further increasing the complexity of the networks, to more accurately model the neuronal organisation of the brain.

Interested? Read Sarah Farley’s full Chemistry World article here or download the Lab on a Chip paper:

Axon diodes for the reconstruction of oriented neuronal networks in microfluidic chambers
Jean-Michel Peyrin, Bérangère Deleglise, Laure Saias, Maéva Vignes, Paul Gougis, Sebastien Magnifico, Sandrine Betuing, Mathéa Pietri, Jocelyne Caboche, Peter Vanhoutte, Jean-Louis Viovy and Bernard Brugg
Lab Chip, 2011, Advance Article
DOI: 10.1039/c1lc20014c

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New YouTube Videos

View the new videos on the Lab on a Chip YouTube site using the links below:

A switchable digital microfluidic droplet dye-laser

Electrolysis in nanochannels for in situ reagent generation in confined geometries

Magnetic domain wall conduits for single cell applications

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On the cover: a digital microfluidic method for dried blood spot analysis

On the front cover of Issue 19 is an article from Aaron Wheeler et al. on their new method for the analysis of dried blood spot samples. The method has the potential to offer automation of dried blood samples, which are useful for a number of clinical and pharmaceutical applications due to the small sample sizes involved and ease of storage.  The team have developed a prototype microfluidic system to quantify amino acids in which analytes are extracted, mixed with internal standards, derivatized, and reconstituted for analysis by tandem mass spectrometry.

This hot article was also recently reported on in C&EN.

A digital microfluidic method for dried blood spot analysis
Mais J. Jebrail, Hao Yang, Jared M. Mudrik, Nelson M. Lafrenière, Christine McRoberts, Osama Y. Al-Dirbashi, Lawrence Fisher, Pranesh Chakraborty and Aaron R. Wheeler
Lab Chip, 2011, 11, 3218-3224
DOI: 10.1039/C1LC20524B

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New YouTube Videos

View the new videos on the Lab on a Chip YouTube site using the links below:

Photoreversible fragmentation of a liquid interface for micro-droplet generation by light actuation

DNA-templated assembly of droplet-derived PEG microtissues

A microchip-based model wound with multiple types of cells

Automated cellular sample preparation using a Centrifuge-on-a-Chip

Double-emulsion drops with ultra-thin shells for capsule templates

Pyroelectric Adaptive Nanodispenser (PYRANA) microrobot for liquid delivery on a target

Classification of cell types using a microfluidic device for mechanical and electrical measurement on single cells

Microfluidic baker’s transformation device for three-dimensional rapid mixing

Integrated sieving microstructures on microchannels for biological cell trapping and droplet formation

Microfluidic platform for electrophysiological studies on Xenopus laevis oocytes under varying gravity levels

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RSC e-membership launched

This week, the RSC launched a new product, RSC e-membership, allowing anyone to access an electronic version of Chemistry World through a MyRSC account and to enjoy the benefits of electronic networking via this professional online community for £20/year.

Subscribers to this do not benefit from the professional recognition or any of the other many services and discounts available to RSC Members, but it allows chemists from around the world, many already members of another chemical society in their own country, to benefit from the highly-esteemed content in Chemistry World and the networking opportunities offered from MyRSC, which now stands at over 11,000 members. The RSC e-membership also allows subscribers to join a virtual specialist interest group on MyRSC. If you are interested in joining, please visit www.rsc.org/emembership.

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Rumblings of the big future of small chips heard in Asia

Report from The International Symposium on Microchemistry and Microsystems 2011 (ISMM 2011)

Joong Yull Park, Sang-Hoon Lee and Shuichi Takayama

The International Symposium on Microchemistry and Microsystems 2011 (ISMM 2011), the Asian region forum on Micro Total Analysis Systems (μTAS), was held at a quiet hotel located in the southern part of Seoul, Korea, on June 2-4. Over 400 scientists and professionals arrived from diverse countries not only in Asia, but also from the U.S., the E.U., and beyond bringing with them their recent research advances and visions about the conference theme of: The Future of Miniaturized Systems.

Figure 1. Nanocoral probes docking on a cancer-cell membrane. The highly roughened gold region of the nanocoral increases the molecular adsorption capacity and causes a strong surface-enhanced Raman spectroscopy signal.

The symposium opened with a plenary lecture from Professor Luke P. Lee, UC Berkely. Starting with a history of how stock market price increases paralleled commercialization of key technological breakthroughs, he predicted the future of miniaturized systems in terms of not only technology but potential financial impact as well. He emphasized the increasing need for quantitative biology and medicine and that harnessing micro/nano technology will be key. Considering that several decades were spent to move from vacuum tubes to microscale electronic components embedded in computers, he called upon both patience and hope for biochip and nanotechnology development. Specific research advances presented included Nano Satellites (Figure 1), an exciting concept for using nanoplasmonic particles to explore and visualize the inner space of living cells similar (both in concept and in terms of visual images obtained) to how macro-satellites help explore outer space.1 Combining the phenomenon of plasmon resonance, which is the collective resonant oscillation of electrons in a metal, with nanostructured particles, nanoplasmonic satellites focus and amplify light to nanometer-sized regions to shed new light on signaling pathways and cellular dynamics.

Figure 2. Size-dependent separation of spherical particles and possible rotation behaviors of spherical and nonspherical particles at the branch point.

The other plenary talks on this first day was given by Professor Minoru Seki, Chiba University, who introduced Pinched Flow Fractionation (PFF) and Hydrodynamic Filtration (HDF), a robust method to sort cells and particles by size in milliseconds (Figure 2).2 His presentation also covered calcium alginate gel fibers, anisotropic fibers, droplet-embedded fibers, and sandwich-type fibers generated in microfluidic chips. The anisotropic cross-sectional morphologies of the fibers are promising for guided growth of multiple cell types and thus for 2D/3D cell assembly which is required for tissue regeneration. His contributions are timely given the accelerating growth of cell-based therapies and associated increasing needs for cell sorting and analysis. Professor Bingcheng Lin, Chinese Academy of Sciences, proclaimed that we are ready for the future, to move microfluidics research to the next stage with increased applications, solving real-world problems, and realizing more commercialization. In the invited session, gold and silver nanoparticle-based colorimetric assay for protein and nucleic acids was presented by Professor Xiaodi Su, Institute of Materials Research and Engineering, Singarpore. The method utilizes metal nanoparticles’ unique optical properties and localized surface plasmon resonance (LSPR) for highly sensitive and lable-free detection.

Figure 3. Left: ‘Suspended’ nanofibers connect six carbon posts. Right: Dilution module consists of input channel, dilution chamber, pillars, side channel, and output channel. Blue arrows indicate the flow direction, the dashed orange arrows the recirculatory mixing. Output droplets define a digital concentration gradient.

Plenary talks for the 2nd day were given by Professor Marc Madou, UC Irvine, and Andrew J. deMello, Imperial College London. Professor Madou introduced a way to combine photolithography, near-field electrospinning, and carbonization to pattern suspended carbon nanowire structures over incredible distances (left, Figure 3).3 These C-MEMS and C-NEMS structure were used for interdigitated electrode sensors, glucose sensors, bio-fuel cells and smart batteries. Keywords that describe Professor deMello’s lecture include ‘controlled droplet fusion’, ‘serial dilution on the microscale’, and ‘compartmentalization of single cell’. He showed a dilution module for high-throughput screening using droplet-based microfluidics (right, Figure 3), and demonstrated a homogeneous DNA-binding assay using this system. This digital concentration gradient.4 Other invited speakers included Professor Kahp-Yang Suh, Seoul National University, who introduced research opportunities in the area of ‘Body on a Chip’. One target organ he introduced was a kidney-on-a-chip. By combining microfluidics, advanced patterning technology called CFL (capillary force lithography), and multi-layer microfluidic device (MMD), a microfluidic bio-artificial kidney system was realized.5 The shear stress generated by flow in microfluidic channels is a necessary physiological stimulus for kidney cells along with hormonal stimulation. The biophysical and biochemical stimuli work synergetically to induce proper functioning of kidney cells in vitro. In other presentations, Professor Danny van Noort from the National University of Singapore, gave an aptly titled talk right before lunch about ‘Fish & Chips’. His micro fish tank array system (microaquarium) was cleverly designed to efficiently study fish embryo on a chip.

The last day of ISMM 2011 was opened by Professor Dong-Pyo Kim’s (Chungnam National University) plenary talk. He highlighted the importance of materials science and development. Despite the broad use of PDMS, particularly in academia, there is a critical need for alternate materials. For example, Professor Kim introduced various solvent resistant microreactors. He microfabricated PDMS, polyimid film and functional inorganic polymers by various lithographic techniques. The burgeoning field of microreactor technology is already starting to make a significant impact for industrial as well as benchside use, said Professor Kim.

Figure 4. A single-molecule DNA translocates through a nanopore where a pair of nanoelectrodes fabricated to scan the tunnelling current across each nucleotide for label-free base sequence read-out.

Other highlights included description of the latest in single molecule DNA manipulation and sequencing technologies by Professors Kyubong Jo, Steven Soper and Tomoji Kawai. Professor Kawai, Osaka University, specifically introduced the next generation of DNA sequencing technology that utilizes gating nanopores. Two configurable nanoelectrodes enables the electrical detection of single nucleotides (Figure 4).6 Electron transport through single nucleotides occurs not by changes in the ionic current flowing parallel to the nanopore but by changes in the electric current flowing between the nanogap electrodes.

ISMM 2011 was organized in conjunction with the KBCS (Korea BioChip Society) with Professor Sang-Hoon Lee, Korea University serving as the general chair. The successful three days symposium closed on 4th June 2011. A cultural highlight of ISMM 2011 was a traditional Korean performance called Sa-mul-no-ri (Figure 5). ‘Sa-mul’ means ‘four objects’ (four traditional drums that represent thunder, wind, cloud, and rain) and ‘no-ri’ means ‘play’. The rapid and powerful drumbeat not only coordinated the dancing performers but also got the audience moving their bodies. This exciting and interactive performance of traditional music and dance symbolized well the vibrant field of miniaturized systems that we experienced at ISMM 2011 with fast-paced discoveries, cross-disciplinary interactions, and increasing collaboration with ‘audiences’ outside the micro/nanotechnology ‘performers’ including industry. It also felt like the rumblings of the exciting future where ‘play’ between the ‘four objects/subjects’ of medicine, chemistry, biology, and engineering opens unprecedented opportunities.

Figure 5. Dancing to the rhythm of Korean drums at ISMM 2011.

References
1 L. Y. Wu, B. M. Ross, S. Hong and L. P. Lee, Small, 2010, 6, 503-507.
2 S. Sugaya, M. Yamada and M. Seki, Biomicrofluidics, 2011, 5, 24103.
3 G. S. Bisht, G. Canton, A. Mirsepassi, L. Kulinsky, S. Oh, D. Dunn-Rankin and M. J. Madou, Nano Lett, 2011, 11, 1831-1837.
4 X. Niu, F. Gielen, J. B. Edel and A. J. deMello, Nat. Chem., 2011, 3, 437-442.
5 K. J. Jang and K. Y. Suh, Lab Chip, 2010, 10, 36-42.
6 M. Tsutsui, M. Taniguchi, K. Yokota and T. Kawai, Nat. Nanotechnol., 2010, 5, 286-290.

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Lab on a Chip in C&EN!

A Lab on a Chip paper from Aaron Wheeler and coworkers at the University of Toronto has featured in the magazine Chemical & Engineering News – New Method Is Spot On.

The article describes the application of microfluidic techniques to the analysis of dried blood spot samples – read the original paper here:

A digital microfluidic method for dried blood spot analysis
Mais J. Jebrail, Hao Yang, Jared M. Mudrik, Nelson M. Lafrenière, Christine McRoberts, Osama Y. Al-Dirbashi, Lawrence Fisher, Pranesh Chakraborty and Aaron R. Wheeler
Lab Chip, 2011, Advance Article
DOI: 10.1039/C1LC20524B

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Top ten most accessed articles in July

This month sees the following articles in Lab on a Chip that are in the top ten most accessed:

Disposable microfluidic substrates: Transitioning from the research laboratory into the clinic
Jason S. Kuo and Daniel T. Chiu
Lab Chip, 2011, 11, 2656-2665
DOI: 10.1039/c1lc20125e

‘Fab-Chips’: a versatile, fabric-based platform for low-cost, rapid and multiplexed diagnostics
Paridhi Bhandari, Tanya Narahari and Dhananjaya Dendukuri
Lab Chip, 2011, 11, 2493-2499
DOI: 10.1039/c1lc20373h

Photoreversible fragmentation of a liquid interface for micro-droplet generation by light actuation
Antoine Diguet, Hao Li, Nicolas Queyriaux, Yong Chen and Damien Baigl
Lab Chip, 2011, 11, 2666-2669
DOI: 10.1039/c1lc20328b

Integrated microfluidic array plate (iMAP) for cellular and molecular analysis
Ivan K. Dimov, Gregor Kijanka, Younggeun Park, Jens Ducrée, Taewook Kang and Luke P. Lee
Lab Chip, 2011, 11, 2701-2710
DOI: 10.1039/c1lc20105k

A self-heating cartridge for molecular diagnostics
Changchun Liu, Michael G. Mauk, Robert Hart, Xianbo Qiu and Haim H. Bau
Lab Chip, 2011, 11, 2686-2692
DOI: 10.1039/c1lc20345b

Integrated immunoassay using tuneable surface acoustic waves and lensfree detection
Yannyk Bourquin, Julien Reboud, Rab Wilson, Yi Zhang and Jonathan M. Cooper
Lab Chip, 2011, 11, 2725-2730
DOI: 10.1039/c1lc20320g

Research highlights
Šeila Selimović and Ali Khademhosseini
Lab Chip, 2011, 11, 2651-2652
DOI: 10.1039/c1lc90074a

Microfluidic fluorescence in situ hybridization and flow cytometry (µFlowFISH)
Peng Liu, Robert J. Meagher, Yooli K. Light, Suzan Yilmaz, Romy Chakraborty, Adam P. Arkin, Terry C. Hazen and Anup K. Singh
Lab Chip, 2011, 11, 2673-2679
DOI: 10.1039/c1lc20151d

DNA detection with a polymeric nanochannel device
Paola Fanzio, Valentina Mussi, Chiara Manneschi, Elena Angeli, Giuseppe Firpo, Luca Repetto and Ugo Valbusa
Lab Chip, 2011, 11, 2961-2966
DOI: 10.1039/c1lc20243j

Paper-based piezoresistive MEMS sensors
Xinyu Liu, Martin Mwangi, XiuJun Li, Michael O’Brien and George M. Whitesides
Lab Chip, 2011, 11, 2189-2196
DOI: 10.1039/c1lc20161a

Why not take a look at the articles today and blog your thoughts and comments below.

Fancy submitting an article to Lab on a Chip? Then why not submit to us today or alternatively email us your suggestions.

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