Archive for the ‘Hot Articles’ Category

HOT article: No separate demodulator for oscillating droplet manipulation

Electrowetting on dielectric-coated electrodes (EWOD) enables manipulation of individual droplets. Rather than direct current, AC-EWOD is used to additionally oscillate droplets for mixing and transport.

For wireless AC-EWOD, magnetic induction with a high frequency signal is needed, however this is above the dynamic range for droplet oscillation and an amplitude demodulator is currently needed in front of the EWOD chip to reduce this below 1 kHz.

In today’s HOT article, collaborators from Gangneung-Wonju National University, Republic of Korea, and University of Pittsburgh, USA, show theoretically and experimentally that an EWOD-actuated droplet actually has the ability to demodulate a high frequency amplitude modulation frequency itself due to the contact angle and does not require external artificial demodulation.

droplet, demodulationThe team point out that this phenomenon is unique in that this is the first physical entity to show visible demodulation behaviour. They briefly show that this demodulating functionality is not applicable with frequency modulation signals. Further investigation will focus on the possible range of signal that can be applied and successfully transmitted to the droplet and recovered by the inherent demodulation.

Read the theoretical and experimental explanation in full, as this HOT article is free to access for four weeks*:

Inherent amplitude demodulation of an AC-EWOD (electrowetting on dielectric) droplet
Myung Gon Yoon, Sang Hyun Byun and Sung Kwon Cho
DOI: 10.1039/C2LC41043E

*Free access to individuals is provided through an RSC Publishing personal account. Registration is quick, free and simple

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LOC Issue 8 now online: Art in Science

The winner of the 2012 Art in Science Award presented at October’s MicroTas meeting was Yi Zhang, from Johns Hopkins University, USA and the striking winning image is featured on the outside front cover of Issue 8!

Read what’s in the issue here

A description of the winning image and advice on what makes a worthy Art in Science submission are discussed in the editorial by Michael Gaitan from NIST, USA, and Harp Minhas, Editor of LOC, who were part of the award selection committee.

The Art in Science of microTAS
Michael Gaitan and Harp Minhas
DOI: 10.1039/C3LC90026F


In keeping with the artistry of the front cover, work from Shoji Takeuchi et al. in Japan is featured on the inside front cover of Issue 8. In this paper, they address the problem of how to exchange the solution within a droplet for a new solution, for example to introduce membrane proteins or to wash-out applied chemicals during ion channel analysis. They use microfluidic channels to carry out solution exchange by droplet contact in under 20 seconds with the membrane still intact. Cover articles are free to access for 6 weeks*!

Droplet-based lipid bilayer system integrated with microfluidic channels for solution exchange
Yutaro Tsuji, Ryuji Kawano, Toshihisa Osaki, Koki Kamiya, Norihisa Miki and Shoji Takeuchi
DOI: 10.1039/C3LC41359D


The back cover features the laboratory of Sergey Shevkoplyas at Tulane University, USA. The communication by this laboratory describes their simple point-of-care test for sickle cell disease using characteristic patterns made by blood samples on paper, which can even differentiate between sickle cell disease and those healthy people with sickle cell traits.

A simple, rapid, low-cost diagnostic test for sickle cell disease
Xiaoxi Yang, Julie Kanter, Nathaniel Z. Piety, Melody S. Benton, Seth M. Vignes and Sergey S. Shevkoplyas
DOI: 10.1039/C3LC41302K


This issue also includes plenty of HOT research and a focus article from Tony Huang on the more unconventional applications of microfluidics:

Unconventional microfluidics: expanding the discipline
Ahmad Ahsan Nawaz, Xiaole Mao, Zackary S. Stratton and Tony Jun Huang
DOI: 10.1039/C3LC90023A

Programmable parylene-C bonding layer fluorescence for storing information on microfluidic chips
Ata Tuna Ciftlik, Diego Gabriel Dupouy and Martin A. M. Gijs
DOI: 10.1039/C3LC41280F

Engineering of functional, perfusable 3D microvascular networks on a chip
Sudong Kim, Hyunjae Lee, Minhwan Chung and Noo Li Jeon
DOI: 10.1039/C3LC41320A

In situ synthesis of silver nanoparticle decorated vertical nanowalls in a microfluidic device for ultrasensitive in-channel SERS sensing
Joseph Parisi, Liang Su and Yu Lei
DOI: 10.1039/C3LC41249K

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Innovative cell culture and analysis microdevices

Here we have two HOT articles for you to read, both of which are free to access for the next 4 weeks*:

Researchers at North Carolina State University, USA, integrate microelectrodes into a neuron culture platform creating a single device with which cells can be electrically stimulated and their behaviour recorded simultaneously for scientific experiments. They do this using gallium and its alloys, which are liquid at room temperature and flow into microchannels to create the microelectrodes. This integrated biocompatible device avoids the complication of manually aligning the electrodes and provides subcellular accuracy.

Integration of pre-aligned liquid metal electrodes for neural stimulation within a user-friendly microfluidic platform
Nicholas Hallfors, Asif Khan, Michael D. Dickey and Anne Marion
DOI: 10.1039/C2LC40954B

As featured on the outside front cover of Issue 5, HOT article number two is from a team led by Peter Ertl at the Austrian Institute of Technology, Austria, and Siemens AG, Germany. They combine two methods of cell analysis into one miniaturised device for dual-parameter analysis of cell cultures. The first technique is electrical impedance spectroscopy, normally used in analysing adherent cell cultures. The second is optical light scattering, normally used in flow cytometry. The combination of the two to detect light scattering from adherent cells enables rapid identification of cell number variations during culture, assessment of cell adhesion and interactions in physiological conditions. Applications are envisaged in cell–drug interaction assays and cytotoxicity screening. It also identifies intracellular granularity, which indicates apoptosis.

Standardization of microfluidic cell cultures using integrated organic photodiodes and electrode arrays
Verena Charwat, Michaela Purtscher, Sandro F. Tedde, Oliver Hayden and Peter Ertl
DOI: 10.1039/C2LC40965H

*Free access to individuals is provided through an RSC Publishing personal account. Registration is quick, free and simple

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Video of microfluidic origami – digital microfluidics with integrated mass spectrometry to monitor microreactions in real time

Lab on a Chip editorial board member Aaron Wheeler and Andrea Kirby at the University of Toronto enable analysis on-chip with a new device format for digital microfluidics (DMF) based chemical synthesis that they are calling “microfluidic origami”.

The setup allows DMF to be integrated with mass spectrometry for in-line analysis. Offline analysis on the benchtop is particularly troublesome for mass spectrometry as it requires further handling steps and takes further time. There are three devices that have coupled DMF with electrospray ionisation before. However, these either have challenges associated with device fabrication or need external equipment and tricky alignment of device and ESI emitter.

This video from the Wheeler laboratory clearly shows how the device is folded, like origami, and explains how it works.

http://www.youtube.com/watch?v=-lpQhPBlu7M 

The “origami” aspect is down to a folded nanoelectrospray ionization (nanoESI) emitter on a single flexible polyimide film. This work combines previously known concept of folded ESI emitters and that of making DMF devices with flexible substrates to move droplets on non-planar surfaces to get an integrated device on one flexible substrate. They include a two-plate-to-one-plate DMF interface to give ease of droplet delivery from the mixing region to the nanoESI emitter.

They validate the device with a Morita-Baylis-Hilman reaction, monitoring it in-line in real time. This is the first time a digital microfluidic device has been used to monitor chemical synthesis in real time with in-line mass spectrometry.

This HOT article has been made free to access for the next 4 weeks*, so after watching the video you can read the scientific detail of how they fabricated and validated the device:

Microfluidic origami: a new device format for in-line reaction monitoring by nanoelectrospray ionization mass spectrometry
Andrea E. Kirby and Aaron R. Wheeler
DOI: 10.1039/C3LC41431K

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HOT article: Nodes in pore channel create signature to count even the smallest particles in a heterogeneous population

Counting of cells and even smaller particles, such as single molecules of DNA and viruses, can be carried out using resistive-pulse sensing (RPS). The particles move through a pore set up with a flow of current across it. When a particle goes through, it changes the resistance, which can be measured and used to count the particles and even size them. The difficulty is that small molecules in a heterogeneous mixture get lost amongst the large molecules and remain undetected as the pore must be large enough for the largest particle. The signal-to-noise ratio is the limiting factor on sensitivity.

Researchers at the University of California, Berkeley, USA, led by Lydia Sohn present solutions to these limitations in this HOT article with a method they title node-pore sensing (NPS). Instead of one uniform pore width, the microfluidic device has a pore with a sequence of nodes down the length of the pore channel. The nodes in their device are larger than the rest of the channel.  The presence of these nodes means that the device sensitivity is three orders above that of other RPS sensors. The simple method enables the spacing, number and size of these nodes to be changed.

The number and spacing of the nodes changes the normal pulse signal output accordingly, producing a very identifiable corresponding rise and fall pattern. Using this signature, the particle can be detected even with usually problematic signal-to-noise ratios.  By changing the flow rate and specifically designing the node arrangement, this signature pattern can be controlled to distinguish even very small particles through a large pore. The size range of particles that can be measure with the one pore is therefore considerable.

This article is well worth a read, offering numerous advantages over current devices and offering the potential for point-of-care analysis. It’s free to access for the next four weeks*, read it by clicking the link below:

Node-pore sensing: a robust, high-dynamic range method for detecting biological species
Karthik Balakrishnan, George Anwar, Matthew R. Chapman, Trongtuong Nguyen,  Anand Kesavarajud and Lydia L. Sohn
DOI:10.1039/C3LC41286E

*Free access to individuals is provided through an RSC Publishing personal account. Registration is quick, free and simple

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Issue 7 online! The latest HOT miniaturisation research and critical reviews on microfabricated organ systems, nucleic acid amplification and microfluidics in IVF

As highlighted on the outside front cover, physicists, engineers and chemists at the University of Illinois , USA, describe a new laser-based label-free resonant optical biosensor with high resolution and high sensitivity. The difference with this sensor is that they use a photonic crystal resonant reflector surface to introduce optical gain to the sensor from an external source via simulated emission. All of our cover articles are free to access for 6 weeks,* so you can read the full work now:

External cavity laser biosensor
Chun Ge, Meng Lu, Sherine George, Timothy A. Flood, Clark Wagner, Jie Zheng, Anusha Pokhriyal, J. Gary Eden, Paul J. Hergenrother and Brian T. Cunningham
DOI: 10.1039/C3LC41330F

On the inside front cover, researchers at California Institute of Technology, USA, and LeukoDx Inc., Israel, present a point-of-care test for leukocyte counting using a microflow cytometer and fluorescent dye. This method eliminated excessive dilution and sheath flow, giving a minimal needed sample volume.

Four-part leukocyte differential count based on sheathless microflow cytometer and fluorescent dye assay
Wendian Shi, Luke Guo, Harvey Kasdan and Yu-Chong Tai
DOI: 10.1039/C3LC41059E

Work from Tino Frank and Savaş Tay at ETH Zurich is featured on the inside back cover. To improve studies of cell signalling in vitro, this article introduces a simple cell culture platform that can produce programmable diffusion-based gradients using microfluidics based on modifying flow over time. Read it here:

Flow-switching allows independently programmable, extremely stable, high-throughput diffusion-based gradients
Tino Frank and Savaş Tay
DOI: 10.1039/C3LC41076E

The outside back cover highlights the work of Sung Gap Im at KAIST, South Korea. This article is about a doubly cross-linked nano-adhesive system (DCNA) and the team demonstrate fabrication of microfluidic devices with flexible and rigid substrates with high strength and stability. The flexible devices could be manipulated without delamination occurring.

A doubly cross-linked nano-adhesive for the reliable sealing of flexible microfluidic devices
Jae Bem You, Kyoung-Ik Min, Bora Lee, Dong-Pyo Kim and Sung Gap Im
DOI: 10.1039/C2LC41266G

 

In addition to the primary microfluidics research and high number of HOT articles in issue 7, there are also three critical reviews:

Microfabricated mammalian organ systems and their integration into models of whole animals and humans
Jong H. Sung, Mandy B. Esch, Jean-Matthieu Prot, Christopher J. Long, Alec Smith, James J. Hickman and Michael L. Shuler
DOI: 10.1039/C3LC41017J

Thinking big by thinking small: application of microfluidic technology to improve ART
J. E. Swain, D. Lai, S. Takayama and G. D. Smith
DOI: 10.1039/C3LC41290C

Nucleic acid amplification using microfluidic systems
Chen-Min Chang, Wen-Hsin Chang, Chih-Hung Wang, Jung-Hao Wang, John D. Mai and Gwo-Bin Lee
DOI: 10.1039/C3LC41097H

View the whole issue here

*Free access to individuals is provided through an RSC Publishing personal account. Registration is quick, free and simple

 

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How to tickle a cell: on-chip microrobotic mechanical sensor

In the past researchers developed many different microrobots for the mechanical studies of single cells. Some of them require complicated micromanipulators; others can be controlled with optical tweezers, but are limited in the force that they exert and so are inapplicable to cells with stiff cell walls.

A team from institutes in the USA and Japan, including MIT and RIKEN, describes in a recent Lab Chip article a new type of microrobot that can be installed in a microfluidic chip and used for mechanical stimulation of single cells. In this device a robotic arm with a mechanical probe at its end is built from a magnetic material and can be moved within the structure of the microchip by applying magnetic force. This design means that there are no complex mechanical assemblies necessary to move the arm. The probe itself consists of a microneedle placed on a flexible base. The force applied with the needle is measured by the extent of base deformation.

Tomohiro Kawahara and colleagues built a microchip with the microrobotic probe in its main chamber and use it to study the reaction of small single-cellular organisms, diatoms, to mechanical stimulus. They are able to adjust the applied force so that the cell itself isn’t damaged. Upon stimulation they observe agglomeration of chloroplasts into two separate groups. They also quantify the stimulus required for chloroplast assembly to occur.

Although the experiment described by Kawahara and colleagues is a simple proof-of-concept, it does mean that a wealth of phenomena can now be examined in more detail than ever before. Another example where mechanical stimulus elicits a response is in the small organism dinoflagellate, which bioluminesces when mechanically probed. The response of many cells to this sort of stimulus mimics their response to attack by pathogens and Miyawaki’s microrobot now opens the way to studying such responses.

This HOT article is free to access for the next 4 weeks*, just click on the link below:

On-chip microrobot for investigating the response of aquatic microorganisms to mechanical stimulation
Tomohiro Kawahara, Masakuni Sugita, Masaya Hagiwara, Fumihito Arai, Hiroyuki Kawano, Ikuko Shihira-Ishikawa and Atsushi Miyawaki
DOI: 10.1039/C2LC41190C

 *Free access to individuals is provided through an RSC Publishing personal account. Registration is quick, free and simple

Published on behalf of Rafal Marszalek, Molecular BioSystems web science writer. Rafal is an Assistant Editor of Genome Biology at BioMed Central

 

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HOT review: Forming the wiring of the nervous system – discovering the mechanisms of axon guidance through new technologies

Today’s HOT article is a review article that was featured on the front cover of our Neuroengineering themed issue.

In this review, Santiago Costantino et al. at the University of Montreal and McGill University, Canada, critically discuss the most recent insights into axon guidance that have been enabled by developments in methods and technologies for engineered cell substrates.

This review includes:

  1. Extracellular cues and growth cones
  2. Historical background
  3. The stripe assay in discovery of guidance cues and signalling mechanisms
  4. Microcontact printing – development from the stripe assay
  5. Insights via microfluidics
  6. Studies using laser-assisted printing and patterning 3D hydrogels

The focus is on the biological insights into how axons recognise and interpret external signals in order to reach their synaptic target that have come out of using these technologies, rather than the development of the technology itself. This cover article is still free to access for another couple of weeks*, read it now by clicking the link below:

Engineered cell culture substrates for axon guidance studies: moving beyond proof of concept
Joannie Roy, Timothy E. Kennedy and Santiago Costantino
DOI: 10.1039/C2LC41002H

*Free access to individuals is provided through an RSC Publishing personal account. Registration is quick, free and simple

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Welcome to Lab on a Chip Issue 6! A microrobot, adaptive coatings, protein detection, flow cytometry, a critical review and the final Acoustofluidics paper

On the outside front cover is a Technical Innovation from Oliver Hayden, Michael Helou and co-workers in Germany describing a magnetic time-of-flight flow cytometry workflow for point-of-care tests, integrating sample preparation with the use of superparamagnetic labels:

Time-of-flight magnetic flow cytometry in whole blood with integrated sample preparation
Michael Helou, Mathias Reisbeck, Sandro F. Tedde, Lukas Richter, Ludwig Bär, Jacobus J. Bosch, Roland H. Stauber, Eckhard Quandt and Oliver Hayden
DOI: 10.1039/C3LC41310A


 

The inside front cover highlights work by Martin Gijs’s team at EPFL, Switzerland, on a microfluidic method for ultra-sensitive protein detection in serum using magnetic beads:

Attomolar protein detection using a magnetic bead surface coverage assay
H. Cumhur Tekin, Matteo Cornaglia and Martin A. M. Gijs
DOI: 10.1039/C3LC41285G


Mengsu Yang and co-workers at the City University of Hong Kong are advertised on the back cover, which illustrates their research on monitoring of intracellular calcium signals after mechanical stimulation using a single integrated microfluidic device:

Microfluidics study of intracellular calcium response to mechanical stimulation on single suspension cells
Tao Xu, Wanqing Yue, Cheuk-Wing Li, Xinsheng Yao and Mengsu Yang
DOI: 10.1039/C3LC40880A

 

Remember, all of our cover articles are free to access for 6 weeks!*

*Free access to individuals is provided through an RSC Publishing personal account. Registration is quick, free and simple
 


The final paper in our highly interesting Acoustofluidics series of tutorial articles is published in Issue 6. It points out the ability to combine acoustic forces with others for microfluidic applications:

Acoustofluidics 23: acoustic manipulation combined with other force fields
Peter Glynne-Jones and Martyn Hill
DOI: 10.1039/C3LC41369A

Issue 6 also includes a Critical Review on sample preparation for cell analysis technology from Dino Di Carlo et al. at the University of California, USA:

Microfluidic sample preparation for diagnostic cytopathology
Albert J. Mach, Oladunni B. Adeyiga and Dino Di Carlo
DOI: 10.1039/C2LC41104K

HOT articles in Issue 6 include:

On-chip microrobot for investigating the response of aquatic microorganisms to mechanical stimulation
Tomohiro Kawahara, Masakuni Sugita, Masaya Hagiwara, Fumihito Arai, Hiroyuki Kawano, Ikuko Shihira-Ishikawa and Atsushi Miyawaki
DOI: 10.1039/C2LC41190C

Dynamic pH mapping in microfluidic devices by integrating adaptive coatings based on polyaniline with colorimetric imaging techniques
Larisa Florea, Cormac Fay, Emer Lahiff, Thomas Phelan, Noel E. O’Connor, Brian Corcoran, Dermot Diamond and Fernando Benito-Lopez
DOI: 10.1039/C2LC41065F

For more fascinating Lab on a Chip content, read the full issue here

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Constant stretching of DNA in a microfluidic device for higher throughput Genome Sequence Scanning

This HOT article by Robert Meltzer et al. at Pathogenetix Inc., USA, describes new geometries for the stretching funnel in Genome Sequence Scanning that increase DNA throughput by 30 times.

Genome Sequence Scanning (GSS) detects sequence-specific fluorescent tags on DNA fragments. It is used to identify bacteria by first lysing open the bacteria cell to release the DNA, then using a restriction endonuclease enzyme to digest the DNA into smaller fragments. Fluorescent tags are added that recognise specific repeated elements present in all bacterial genomes. GSS characterises the bacterial genome by the spatial distribution of the tags.

genome sequence scanning, GSSThe detection is done in a continuous flow microfluidic device with confocal microscopy. In order to carry out the spatial recognition of the fluorescent tags along the length of the DNA fragment, it needs to be stretched out into a linear form using a funnel. High molecule throughput is important as the detection confidence of this technology relies on observing as many tags as possible in the specified experimental period.

The team looks at the relationship between the funnel taper shape and related parameters, such as fluid velocity and fragment length, to improve the current designs and increase throughput. Their new geometries are able to keep the tension applied to the DNA constant during the detection process. Because DNA fragments come in various lengths, a very important goal is to maximise the range of lengths that can be stretched effectively with the funnel. The influence of channel etch depth on fluid flow, and therefore throughput, is also considered.

You can learn more about the work of Pathogenetix on Genome Sequence Scanning by visiting their website. This HOT article, which was featured on the cover of Issue 2, is free to access for the next 4 weeks* and you can read it by clicking the link below:

High-throughput genome scanning in constant tension fluidic funnels
Joshua W. Griffis, Ekaterina Protozanova, Douglas B. Cameron and Robert H. Meltzer
DOI: 10.1039/C2LC40943G#

*Free access to individuals is provided through an RSC Publishing personal account. Registration is quick, free and simple

 

Keep up to date with the latest Lab on a Chip news and blogs by following us on Twitter! @LabonaChip

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