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A new ‘on-chip’ immunoassay device

Professor Yarmash’s lab at Rutgers University have developed a proof of concept microfluidic device, capable of running multiple immunoassays in parallel. The device allows 32 samples to be assayed simultaneously and multiple analytes can be tested in each sample.

As shown in the diagram below, each sample inlet has a bead trap that contains antibody-conjugated microbeads. These are commercially available, allowing virtually any analyte to be tested. The sample flows over the beads at an optimised rate, allowing the analytes to bind to their specific antibodies. A secondary antibody is added that binds to antibodies complexed to analytes, followed by a fluorescent tag that binds to the secondary antibody. The microbeads are then collected, placed in a 96 well plate, and analysed.

a) diagram and b) photo of the device; c) diagram of valve configuration and flow pathways during the assay; d) key steps in assay.

Device layout and assay principle

The authors assayed several proteins from an in vitro supernatant and their results corroborated well with a standard benchtop immunoassay. Compared to the benchtop standard, the device has significantly reduced sample consumption as well as large reductions in microbead and detection antibody consumption. It has comparable sensitivity to the benchtop standard and has a large working range, meaning that analytes present at different concentrations in the sample can be measured simultaneously. In addition to this, it is compatible with commercial reagents and analyte concentration can be quantified. Although previously published devices have addressed some of these characteristics, this the first example where they are combined into one device.

Moving on from their proof-of-concept study, the Yarmash group hopes to develop a device capable of in vivo measurements. One example they give is analysis of cerebrospinal fluid in rats, an important animal model in Alzheimer’s research, where immunoassays are currently limited by the small volumes available.


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

Development and validation of a microfluidic immunoassay capable of multiplexing parallel samples in microliter volumes
Mehdi Ghodbane, Elizabeth C. Stucky, Tim J. Maguire, Rene S. Schloss, David I. Shreiber, Jeffrey D. Zahn and Martin L. Yarmush
Lab Chip
, 2015,15, 3211-3221
DOI:
10.1039/C5LC00398A

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About the webwriter

Claire Weston is a PhD student in the Fuchter Group, at Imperial College London. Her work is focused on developing novel photoswitches and photoswitchable inhibitors.

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*Access is free until 19/11/2015 through a registered RSC account – click here to register

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Top 10 most accessed Lab on a Chip articles in June 2015

In June 2015, our most downloaded Lab on a Chip articles were:

Shia-Yen Teh, Robert Lin, Lung-Hsin Hung and Abraham P. Lee
DOI: 10.1039/B715524G

Ali Kemal Yetisen, Muhammad Safwan Akram and Christopher R. Lowe
DOI: 10.1039/C3LC50169H

Russell H. Cole, Niek de Lange, Zev J. Gartner and Adam R. Abate
DOI: 10.1039/C5LC00333D

Ching-Hui Lin, Yi-Hsing Hsiao, Hao-Chen Chang, Chuan-Feng Yeh, Cheng-Kun He, Eric M. Salm, Chihchen Chen, Ing-Ming Chiu and Chia-Hsien Hsu
DOI: 10.1039/C5LC00541H

Friedrich Schuler, Frank Schwemmer, Martin Trotter, Simon Wadle, Roland Zengerle, Felix von Stetten and Nils Paust
DOI: 10.1039/C5LC00291E

Mei He, Jennifer Crow, Marc Roth, Yong Zeng and Andrew K. Godwin
DOI: 10.1039/C4LC00662C

Joost F. Swennenhuis, Arjan G. J. Tibbe, Michiel Stevens, Madhumohan R. Katika, Joost van Dalum, Hien Duy Tong, Cees J. M. van Rijn and Leon W. M. M. Terstappen
DOI: 10.1039/C5LC00304K

A. Liga, A. D. B. Vliegenthart, W. Oosthuyzen, J. W. Dear and M. Kersaudy-Kerhoas
DOI: 10.1039/C5LC00240K

A. Wasay and D. Sameoto
DOI: 10.1039/C5LC00342C

Ivo Leibacher, Peter Reichert and Jürg Dual
DOI: 10.1039/C5LC00083A

Interesting read? Let us know your thoughts below.

And remember, you can submit directly to Lab on a Chip!

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New YouTube Videos

Multiplexed Paper Analytical Device for Measuring Airborne Metal Particulates with Distance-Based Detection 



 

Transportation, Dispersion and Ordering of Dense Colloidal Assemblies by Magnetic Interfacial Rotaphoresis 



  
Gecko Gaskets for Self-Sealing and High Strength Reversible Bonding of Microfluidics 

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New You Tube Videos

Generation of stable orthogonal gradients of chemical concentration and substrate stiffness in a microfluidic device 



 

Continuous Transfer of Liquid Metal Droplets Across a Fluid-Fluid Interface Within an Integrated Microfluidic Chip 




A flow-free droplet-based device for high throughput polymorphic crystallization 

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Microfluidic Applications

Lab on a Chip Industry Workshop

Microfluidic Applications

Join our event on Facebook and find out who else is attending!

August 2-3 2014 in Dalian, China

This workshop focuses on the innovative developments in Lab-on-a-Chip technology and the applications of microfluidics in diagnostics, biological, material, pharmaceutical, and environmental sciences. For more information, please visit the official webpage.

Register now – deadline is July 15th 2014

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Reprogrammable microfluidic chips

A microfluidic chip with channels that can be programmed then reset and reconfigured has been developed by scientists from France and Japan.

Water is dispensed into chip reservoirs. By selectively switching on electrodes, water is manipulated to carve out the channels

Water is dispensed into chip reservoirs. By selectively switching on electrodes, water is manipulated to carve out the channels

In recent years, scientists from across of the globe have developed a plethora of microfluidic chips to perform a variety of tasks, from PCR to cell sorting. However, a serious drawback of microfluidic technologies is that each application requires a unique arrangement of inlets, outlets and microchannels, so microfluidic chips are usually specific to one particular purpose. This, combined with the time-consuming and costly manufacturing processes required to construct microfluidic devices, makes the idea of a reprogrammable chip very attractive.

Read the full article here at Chemistry World.

Programmable and reconfigurable microfluidic chip
Raphaël Renaudot, et al.
Lab Chip, 2013, Accepted Manuscript
DOI: 10.1039/C3LC50850A, Paper

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Lab on a Chip Co-hosts EU-Korea Microfluidics Workshop

We are very pleased to announce that Lab on a Chip will once again Co-host the third EU-Korea Workshop on microfluidics, focusing on “Emerging Microfluidic Platform Technologies: From Biosciences to Applications”.

Please come along and see us at the meeting, which will be held in Postech International Centre, Pohang, Korea. The workshop takes place on October 3rd to 5th, 2013.

Meet the Editor and International speakers:

Jean-Louis Viovy, Institute Curie, France
Andreas Manz, KIST, Europe
Dongpyo Kim, Pohang, Koreas
Chris Abell, Cambridge, UK
Noo Li Jeon, Seoul, Korea
Sabeth Verpoorte, Groningen, Netherlands
Hywel Morgan, Southampton, UK
Petra Dittrich, ETH Zurich, Switzerland
Sanghyun Lee, FEMTOLAB, Korea
Samuel Sanchez, Max-Planck, Germany
Yoon Kyoung Cho, UNIST, Korea
Francois Leblanc, CEO Fluigent

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Lab-on-a-Chip: The Most Cited Articles of 2010 and 2011

Lab-on-a-Chip would like to present the most cited articles of 2010 and 2011! We would like to use this opportunity to highlight some of the excellent work that the miniaturisation community is producing right now, and to congratulate our authors on their fantastic achievements.    

As of now, all of the below articles will be free for 4 weeks (until Monday 16th Sept),* so make the most of this opportunity to download the full papers!    


 

 

   

Top 3 Cited Reviews:    

  1. CN Baroud et. al.: Dynamics of microfluidic droplets (DOI: 10.1039/c001191f).

    A critical review on the current understanding of the formation, transport and merging of drops in microfluidics. Baroud and colleagues discuss the physical ingredients that differentiate droplet microfluidics from single-phase microfluidics.




      
  2. YK Cho et. al.: Centrifugal microfluidics for biomedical applications (DOI: 10.1039/b924109d).

    A critical review on the biomedical applications of centrifugal microfluidics. Cho and colleagues review current sample-to-naswer systems and the challenges that must be faced before the centrifugal platform can be used as a new diagnostic platform.




      
  3.  GB Lee et. al.: Microfluidic cell culture systems for drug research (DOI: 10.1039/b921695b).

    A tutorial review on microfluidic cell cultures and their use in drug research. The review covers the issues of cell immobilisation, medium pumping and gradient generation, as well as providing examples of practical applications.




      

Top 10 Cited Research Papers:    

  1. GM Whitesides et. al.: Electrochemical sensing in paper-based microfluidic devices (DOI: 10.1039/b917150a).

    A paper on the fabrication and performance of microfluidic paper-based sensing devices. Whitesides and colleagues demonstrated that their paper-based electrochemical devices are capable of quantifying concentrations of various analytes, including heavy metal ions and glucose.




      
  2. D Di Carlo et. al.: Sheathless inertial cell ordering for extreme throughput flow cytometry (DOI: 10.1039/b919495a).

    A paper which demonstrates the use of a microfluidic device for flow-cytometry with extreme throughput. Di Carlo and colleagues demonstrated 86-97% cell counting sensitivity and specificity.


     


      
  3. A Ozcan et. al.: Compact, light-weight and cost-effective microscope based on lensless incoherent holography for telemedicine applications (DOI: 10.1039/c000453g).

    Ozcan and colleagues demonstrate a lensless on-chip microscope weighing only approx. 46 g and dimensions smaller than 5 cm3. The microscope achieves subcellular resolution and may offer a cost-effective tool in the development of portable medicine.


      
  4. D Di Carlo et. al.: Deformability-based cell classification and enrichment using inertial microfluidics (DOI: 10.1039/c0lc00595a)


  5. BJ Kirby et. al.: Capture of circulating tumor cells from whole blood of prostate cancer patients using geometrically enhanced differential immunocapture (GEDI) and a prostate-specific antibody (DOI: 10.1039/b924420d)


  6. A Ozcan et. al.: Lensfree microscopy on a cellphone (DOI: 10.1039/c003477k)


  7. CF Carlborg et. al.: A packaged optical slot-waveguide ring resonator sensor array for multiplex label-free assays in labs-on-chips (DOI: 10.1039/b914183a)


  8. T Franke et. al.: Surface acoustic wave actuated cell sorting (SAWACS) (DOI: 10.1039/b915522h)


  9. JL Osborn et. al.: Microfluidics without pumps: reinventing the T-sensor and H-filter in paper networks (DOI: 10.1039/c004821f)


  10. LG Griffith et. al.: Perfused multiwell plate for 3D liver tissue engineering (DOI: 10.1039/b913221j)


     

*free through an RSC publishing personal account  

 

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Look Mum, no pumps!

GA

Richard Crooks and colleagues, researchers at the University of Texas, Austin developed a way to locally concentrate and move analytes using internal bipolar electrodes (bypassing the need for an outside driver of fluid flow). Electrodes printed on the bottom of the microfluidic channels create controllable gates which balance the convective and electrokinetic forces acting on charged sample molecules. A single DC power supply and controller box is needed to open/close these gates to deliver analytes to different regions of the chip.­­

Crooks and his group have extensively investigated bipolar electrochemistry theory and in this paper demonstrate the use of bipolar electrodes to separate, enrich, and transport ­­­­­bands of analytes in microfluidic channels. Electric potentials applied across a channel induce an electric field within the buffer whilst conductive substrates present on the floor of the microchannel also adopt a potential between their two poles. H+ ions within the buffer are partially neutralized by electrogenerated OH- and thus regions of ion depletion appear. These depletion zones attract charged analytes from the solution to maintain the charge gradient induced by the electric field (the speed of electromigration of analytes to the depletion zone is proportional to the electric field). Bipolar electrodes on the channel bottom contain their own local field and so analytes concentrate in these areas, leading to enrichment near the electrodes.

In this work, Crooks and his team demonstrate separation and enrichment of two common fluorescent dyes:  BODIPY2- and MPTS3-. The two dye bands are then directed to two separate reservoirs. In previous papers, the group focused on optimizing enrichment and achieved enrichment rates of up to 0.57 BODIPY2 1, . The current extension and integration of online separation and enrichment achieves comparable rates of enrichment, 0.11 and 0.31 fold/second for BODIPY and MPTS, respectively, while also enabling control over separating analytes of different electromobility (μep) and transporting these bands to designated areas of the device.

To create the devices presented, the group used conventional photolithography techniques to pattern gold bipolar passive electrodes (BPEs) on glass and bonded PDMS channels on top of the regions. This method can be easily multiplexed as additional BPEs can be activated to guide separated and enriched analytes to different areas of the chip.

 References:

1 R. K. Anand, E. Sheridan, D. Hlushkou, U. Tallarek and R. M. Crooks, Lab on a Chip, 2011, 11, 518-527.

Electrochemically-gated delivery of analyte bands in microfluidic devices using bipolar electrodes
Karen Scida, Eoin Sheridan and Richard M. Crooks, Lab Chip, 2013, 13, 2292-2299.
DOI: 10.1039/c3lc50321f

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