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With the Introducing series and other exciting news on the blog in the last couple of weeks, we’ve had no time for HOT articles. Here are three in brief all at once and all free to access for 4 weeks*!

Aqueous two-phase microdroplets with reversible phase transitions
Jonathan B. Boreyko, Prahya Mruetusatorn, Scott T. Retterer and C. Patrick Collier 
DOI: 10.1039/C3LC41122B

 2. As featured on the colourful back cover of Issue 7, Sung Gap Im’s group at KAIST, South Korea, have developed a doubly cross-linked nano-adhesive system (DCNA). The aim was a super-strong adhesive system resistant to tough chemical and thermal conditions. They use initiated chemical vapour deposition (iCVD) to demonstrate their new secure sealing technique in the fabrication of microfluidic devices with flexible and rigid substrates with high strength and stability. This is doubly cross-linked due to the epoxy groups on both sides of the substrates, giving strong adhesion.

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

 3. The third and final HOT article featured on the inside back cover of Issue 7 comes from Savaş Tay and Tino Frank at ETH Zurich, Switzerland. The cell culture platform in this HOT article is able to support a programmable diffusion-based gradient generator. Long-term experiments with 30 different gradients could be done in parallel. The microfluidic chip uses membrane valves and automation to reduce error and increase simplicity. A wide variety of cell types can be cultured in this total analysis system in flow-free conditions.

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

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

Research from SangHoon Lee et al. on a new 3D liver on a chip that enables more detailed study of the paracrine signalling effects on liver tissue function is featured in Chemistry World today!

Read the Chemistry World article here, including independent comment from Gretchen Mahler at Binghamtom University, US. An excerpt is below:

“Researchers in South Korea have developed a three-dimensional liver model that can recreate cell signalling within the organ. The liver on a chip could cut tests on animals by providing an accurate artificial model of how the organ responds to new drugs.The liver contains two kinds of cells. 80% are hepatocytes and the remaining 20% are non-parenchymal cells, including hepatic stellate cells (HSCs). HSCs work with hepatocytes when the liver is damaged, playing a vital role in liver regeneration. Interactions between HSCs and hepatocytes are not well understood, but both direct cell–cell contact and short distance cell–cell signalling, called paracrine signalling, are known to be involved. Despite numerous artificial liver models, no study has yet looked at paracrine influence alone.”

  Design concept (top) and operation mechanism (bottom) of the chip

 Spheroid-based three-dimensional liver-on-a-chip to investigate hepatocyte–hepatic stellate cell interactions and flow effects
Seung-A Lee, Da Yoon No, Edward Kang, JongIl Ju, Dong-Sik Kim and SangHoon Lee  
DOI: 10.1039/C3LC50197C

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.

The 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

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

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.

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