Shrinking Lab-on-a-Chip to Lab-in-a-Tube

Throughout a series of Lab on a Chip Focus Articles Samuel Sánchez, research group leader at Max Planck Institute for Intelligent Systems and recently elected as “innovator of the year 2014”, will be highlighting cutting-edge reports based on miniaturized devices that bridge functional materials and bio-related applications. And first up we have…Lab-in-a-Tube!

Lab-on-a-chip already scales down several components and integrates them into one device, but now scientists are working toward shrinking this further to develop entire laboratories inside an ultra-compact architecture such as a small tube. Samuel discusses the concept and advantages of the lab-in-a-tube before highlighting remarkable cell studies that have already been performed using microtubes.

Lab-in-a-tube systems can combine several functionalities such as optical or electrochemical sensing and is therefore used in various detection systems. Samuel describes the developments in this area, leading to the fabrication of a highly sensitive rolled-up optofluidic ring resonator – fully integrated into lab-on-a-chip devices of course!

Label-free detection systems using the lab-in-a-tube concept

Finally, Samuel discusses the challenges of controlling fluid flow at the micro scale and the use of self-powered on-chip micropumps. As one of Samuel’s main interests, catalytic micropumps will be discussed further in an upcoming Focus Article.

Samuel’s full article ‘Lab-in-a-tube systems as ultra-compact devices’ can be downloaded for free* on our website. We hope you enjoy reading his summary of recent advances in this new and exciting concept of chip integration.

Don’t miss Samuel’s next focus article – register for our e-alerts now!

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More about Samuel Sánchez

Samuel earned his PhD in Analytical Chemistry from the Autonomous University of Barcelona in 2008. After a short period as an Assistant Professor, he worked in Japan at the National Institute for Materials Science. In 2010 he moved to the Institute for Integrative Nanoscience at the Leibniz Institute in Dresden where he was leading the “Biochemical Nanomembranes” group. He is now leading the independent research group at the Max Planck Institute for Intelligent Systems. Samuel has received several awards for his work including the Guinness World Record® for “The smallest man-made jet engine” in 2010, the IIN-IFW Research Prize 2011, the ERC-Starting Grant 2012 “Lab-in-a-tube and Nanorobotic Biosensors (LT-NRBS).” Recently, Samuel has been named as Spain’s top innovators under 35 by the Spanish edition of the journal MIT Technology Review.

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When microfluidics meets inkjet printing

Alphonsus Ng @Wheeler_Lab writes more…

Since its inception over 50 years ago, inkjet printing has become the most widely adopted method for the reproduction of images and text on paper. Inherently a microfluidic technology, inkjet printing is a process in which individual ink droplets, between 10 to 100 µm diameters, are placed at software-configurable locations on a substrate. The resulting dots can combine to create photo-quality images with resolutions of up to several thousand dots per inch. Such exquisite precision and flexibility make inkjet printing particularly attractive for the scalable fabrication of fine features. Indeed, in addition to coloured inks, this technology has also been adapted to deposit a wide range of materials for manufacturing, including metals, ceramics, polymers, and even biological cells.1

Not surprisingly, the lab on a chip community is also beginning to leverage printing technologies for the fabrication of microfluidic components.2 However, this is not straightforward because the quality of the printed features often depends on the interaction of the ink droplets with the substrate material. Since microfluidic devices are predominantly prototyped using polydimethylsiloxane (PDMS),3 recent research has focused on the development of PDMS-compatible methods for inkjet printing.

In one example, Profs Dachao Li at the Tianjin University, China and Robert C. Roberts at the University of Hong Kong used inkjet printing to form robust silver microelectrodes on PDMS-based microfluidics for glucose sensing.4 In forming these electrodes, the PDMS material posed two challenges: 1) poor adhesion of silver to PDMS inhibited robust electrode formation and, 2) the inherent hydrophobicity of PDMS promoted coalescence of neighboring ink droplets, which impaired the precision of printed features.

To overcome these challenges, the researchers modified the substrate using (3-Mercaptopropyl)trimethoxysilane, a coupling reagent that presents thiol groups on the PDMS surface. The thiol groups not only served as covalent anchoring sites for the inkjet-printed silver but also increased the wettability of the ink droplet, which improved the precision of the printed features.

Remarkably, the printed electrodes formed on these substrates tolerated very harsh stress tests, including immersion in water, exposure to high pressure air stream, and even ultrasonication. This new fabrication strategy enabled the team to create an all-in-one PDMS system with fluid handling and a three-electrode electrochemical cell for transdermal detection of glucose (Picture 1).

In another example, Profs Yanlin Song and Fengyu Li at the Chinese Academy of Sciences, China developed an elegant inkjet-printed method 5 for the fabrication of enclosed PDMS microchannels. This process conventionally requires at least 4 steps: 1) create a solid template via photolithography, 2) cast PDMS prepolymer mixture in the template, 3) cure and separate the PDMS from the template, and 4) bond the molded PDMS to a substrate.

To simplify this procedure, the researchers implemented a liquid template formed by inkjet-printing (Picture 2). Here, an immiscible liquid pattern is printed directly on a pool of PDMS prepolymer solution. Within seconds, the liquid spontaneously submerges below the prepolymer solution and acts as a template. Upon heating, the polymer solidifies while the liquid template evaporates, leaving behind an enclosed PDMS microchannel device.

In the development of this method, one major challenge was maintaining the stability of the liquid template in the prepolymer solution. Due to surface tension, printed liquid templates tend to break up and relax into discontinuous spherical droplets.  Although this instability can be inhibited by increasing the liquid viscosity, high viscosities are not compatible with inkjet printing. To address this challenge, the researchers used an ink whose viscosity is tunable by temperature. At room temperature, the ink has relatively low viscosity (10 centipoise), which is compatible with inkjet printing. When the ink is printed on a cooled (3-4oC) pool of prepolymer solution, the viscosity of the liquid increases dramatically (>40 centipoise), which enabled the formation of a stable liquid template with no breakages.

This inkjet-printed approach enabled the formation of remarkably versatile PDMS microchannels. The diameters of the fabricated channels can range from 100 to 900 µm just by changing the template design. In addition, the interior surface of the channel can be modified by including vinyl-terminated functional molecules in the ink composition, which covalently incorporates in the PDMS matrix during thermal curing. Applying this technique with vinyl-terminated poly(ethylene glycol)methacrylate molecules, the researchers effortlessly imbue their devices with protein fouling resistance.

In summary, the lab on a chip community is beginning to leverage the benefits of inkjet printing in the fabrication of microfluidic components. By engineering the interaction of the ink droplets with the substrate material, researchers are devising innovative ways to fabricate robust electrodes and versatile microchannels without the need for cleanroom facilities and complicated procedures.

1.    I. M. Hutchings and G. D. Martin, Inkjet technology for digital fabrication, John Wiley & Sons, 2012.
2.    P. Tseng, C. Murray, D. Kim and D. Di Carlo, Lab on a Chip, 2014, 14, 1491-1495.
3.    E. Berthier, E. W. K. Young and D. Beebe, Lab on a Chip, 2012, 12, 1224-1237.
4.    J. Wu, R. Wang, H. Yu, G. Li, K. Xu, N. C. Tien, R. C. Roberts and D. Li, Lab on a Chip, 2015, 15, 690-695.
5.    Y. Guo, L. Li, F. Li, H. Zhou and Y. Song, Lab on a Chip, 2015, 15, 1759-1764.

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Free access to February’s HOT Articles

These HOT articles published in February 2015 were recommended by our referees and are free* to access for 4 weeks


On-chip surface acoustic wave lysis and ion-exchange nanomembrane detection of exosomal RNA for pancreatic cancer study and diagnosis
Daniel Taller, Katherine Richards, Zdenek Slouka, Satyajyoti Senapati, Reginald Hill, David B. Go and Hsueh-Chia Chang
Lab Chip, 2015,15, 1656-1666
DOI: 10.1039/C5LC00036J, Paper


Three-dimensional heterogeneous assembly of coded microgels using an untethered mobile microgripper
Su Eun Chung, Xiaoguang Dong and Metin Sitti
Lab Chip, 2015,15, 1667-1676
DOI: 10.1039/C5LC00009B, Paper

A flexible lab-on-a-chip for the synthesis and magnetic separation of magnetite decorated with gold nanoparticles
Flávio C. Cabrera, Antonio F. A. A. Melo, João C. P. de Souza, Aldo E. Job and Frank N. Crespilho
Lab Chip, 2015, Advance Article
DOI: 10.1039/C4LC01483A, Paper

Take a look at our Lab on a Chip 2015 HOT Articles Collection!

*Access is free until 30.04.15 through a publishing personal account. It’s quick, easy and free to register!




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New YouTube videos

Woven Electrochemical Fabric-based Test Sensors (WEFTS): A new class of multiplexed electrochemical sensors 

 
 
Dynamic formation of a microchannel array enables kinesin-driven microtubule transport between separate compartments on a chip 


 
 
Electromechanical cell lysis using a portable audio device: enabling challenging sample preparation at the point-of-care 

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New YouTube Videos

3D-Printed Microfluidic Automation 


 
 
  
Microfluidics-based single cell analysis reveals drug-dependent motility changes in trypanosomes 


 
   
A Fast and Switchable Microfluidic Mixer Based on Ultrasound-Induced Vaporization of Perfluorocarbon 

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Scientists can quickly detect waterborne pathogens using a smartphone!

Web writer Claire Weston, Imperial College London, writes more…

More than half a billion people have to survive with unimproved water, as providing safe drinking water is still a problem in many parts of the developing world. Of the waterborne pathogens, Giardia lambia (G. lambia) is one of the most common intestinal parasites that are difficult to remove using traditional water purification methods. Current methods for their detection take up to two days and require analysis laboratories with trained specialists and expensive equipment. Because of this there is an ongoing effort to design low-cost and field-portable methods that can rapidly analyse large volumes of water.

Ozcan and co-workers at UCLA have developed a method for the detection of G. lambia cysts in water using a light weight attachment to a smartphone. The attachment consists of a fluorescence microscope, aligned to the smartphone camera, and a disposable water sample cassette that can hold 20 mL of water. The whole test can be carried out in just 1 hour, from taking the sample from the source, to receiving the total number of cysts detected in the sample.

The process is relatively simple, with the test sample first being fluorescently labelled and then filtered through a membrane that traps the G. lambia cysts. A fluorescence image is taken and wirelessly transmitted to servers using an app designed by the group. Digital analysis is carried out using a machine learning algorithm that can specifically recognise the cysts over other fluorescent micro-objects. The results of this analysis are then transmitted back to the phone and displayed on the app.

The group were able to achieve an impressive limit of detection of 12 cysts per 10 mL of sample, citing several factors that led to this limit. They have put forward a number of suggestions for how they hope to further improve their system, so it will be interesting to hear more from this group.

To download the full article for free* click the link below:

Rapid imaging, detection and quantification of Giardia lamblia cysts using mobile-phone based fluorescent microscopy and machine learning
Hatice Ceylan Koydemir, Zoltan Gorocs, Derek Tseng, Bingen Cortazar, Steve Feng, Raymond Yan Lok Chan, Jordi Burbano, Euan McLeod and Aydogan Ozcan
DOI: 10.1039/C4LC01358A

*Access is free until 31st March 2015 through a publishing personal account. It’s quick, easy and free to register.

About the web writer

Claire Weston is currently studying for a PhD at Imperial College London, focussing on developing novel photoswitches and photoswitchable inhibitors.

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New You Tube videos

Three-dimensional heterogeneous assembly of coded microgels using an untethered mobile microgripper 


 
 
  
 
Cell culture on microfabricated one-dimensional polymeric structures for bio-actuator and bio-bot applications 


 
 
  
 
A droplet microchip with substance exchange capability for the developmental study of C. elegans  

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Hooked on a Feeling: measuring cell-substrate adhesion with ISFET devices

By developing an ion-sensitive field-effect transistor with small gate dimensions, scientists at the University of Applied Sciences Kaiserslautern in Germany were able to measure cell-substrate adhesion on the single cell scale.

To survive, most mammalian cells attach to other cells and the extracellular environment in order to regulate their growth, proliferation, and migration. Electrical impedance spectroscopy is one way to quantitatively monitor cell-substrate interactions. The strength of cellular adhesion to a substrate with integrated electrodes can be measured by comparing the ratio of the readout voltage to the applied alternating current. Yet this method is limited groups of many cells as the size of the microelectrode must be larger than 100 μm in diameter. Smaller features are subject to greater interface impedance between the electrode and liquid media and this background impedance overwhelms the desired cell-substrate measurements. Suslorapova and colleagues thus used an ion-sensitive field-effect transistor (ISFET) with small gate dimensions to overcome this limitation. The group was able measure the effects of enzymatic digestion with trypsin and an apoptosis-inducing drug on single cell detachment using the ISFET devices with a 16 by 2 square micron gate.

The authors create an equivalent circuit model to interpret recorded impedance spectra from their single cell and small cell groups grown in contact with the field-effect transistor devices. The seal resistance and membrane capacitance parameters which can be extracted from the measured transistor transfer function (TTF) provide measures of cell shape and adhesion to the substrate. Changes in TTF correspond to adhesion of individual cells on top of the ISFET gates. This platform and the model developed to interpret TTF signal opens exciting avenues to monitoring cell adhesion in high throughput yet still at single cell resolution.

Download the full research paper paper for free* for a limited time only!

Electrical cell-substrate impedance sensing with field-effect transistors is able to unravel cellular adhesion and detachment processes on a single cell level
A. Susloparova , D. Koppenhöfer , J. K. Y. Law , X. T. Vu and S. Ingebrandt. Lab Chip, 2015, 15, 668-679. DOI: 10.1039/C4LC00593G

*Access is free until 27.03.15 through a publishing personal account. It’s quick, easy and free to register!

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Google Glass to monitor plant health

‘Okay Glass, image a leaf’

Scientists in the US have developed their very own pair of rose-tinted spectacles by adapting Google Glass to measure the chlorophyll concentration of leaves.

Aydogan Ozcan and his research group at the University of California are passionate about creating new technologies through innovative, photonic methods and are well acquainted with the possibilities of wearable technology in scientific research. Chlorophyll concentration is a handy metric for monitoring plant health and the system devised by Ozcan’s team combines Google Glass with a custom made leaf holder and bespoke software to determine just that.

To read the full article visit Chemistry World.

Quantification of plant chlorophyll content using Google Glass
Bingen Cortazar, Hatice Ceylan Koydemir, Derek Tseng, Steve Feng and Aydogan Ozcan  
Lab Chip, 2015, Advance Article
DOI: 10.1039/C4LC01279H, Paper

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New YouTube Videos

Functional colloidal micro-sieves assembled and guided above a channel-free magnetic striped film

 
 
   
 
Non-equilibrium electrokinetic micromixer with 3D nanochannel networks 


 
   
  
Fabrication of 3D High Aspect Ratio PDMS Microfluidic Networks with A Hybrid Stamp  

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Silver lining for paper Ebola test

Article written by Vicki Davison

Ebola, yellow fever and dengue can be tested for in one go

Researchers in the US have developed a silver nanoparticle-based paper test to simultaneously detect dengue, yellow fever and Ebola. This could provide a cheap and reliable diagnosis for all three diseases, that’s as quick as a home pregnancy test.

The Ebola epidemic in West Africa underscores an urgent need for rapid diagnostics; quick identification and patient isolation can benefit the sick and the healthy. However, dengue, yellow fever and Ebola all initially manifest as a fever and headache, so are easily mixed up.

To read the full article please visit Chemistry World.

Multicolored silver nanoparticles for multiplexed disease diagnostics: distinguishing dengue, yellow fever, and Ebola viruses
Chun-Wan Yen, Helena de Puig, Justina O. Tam, José Gómez-Márquez, Irene Bosch, Kimberly Hamad-Schifferli and Lee Gehrke  
Lab Chip, 2015, Advance Article
DOI: 10.1039/C5LC00055F, Communication

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