Archive for the ‘Reviews’ Category

Optical DNA maps

Just like Google maps, DNA maps can tell us the distance between two genes, and allow us to zoom in on the region of interest. DNA mapping started with human genome project, where DNA sequencing techniques opened a way to unveil the genetic information. However, determining the unique places and repetitions of four “chemical letters” found in our DNA—together known as the genes—is a difficult mission due to temperature, pH, and pressure sensitivity of the molecule.  DNA mapping technology allows for easy identification of large structural variations in DNA and therefore provides long-range information of the genome and can more.

Optical DNA mapping has emerged in the past decade as a powerful alternative to other DNA sequencing techniques since it can easily be applied with reduced risk of DNA damage. Over 100000 basepairs of DNA molecules, which are quite difficult to handle with other techniques, are labeled, stretched, and rendered in a single image. The stretching part is done using nanochannels (and therefore lab-on-a-chip technology), while the labeling part can be done by either enzymatic or affinity-based techniques (Figure 1). The concept and applications of optical DNA mapping has recently been very well explained in a tutorial review written by Vilhelm Müller and Fredrik Westerlund from Chalmers University of Technology in Sweden.

In enzymatic labelling nucleotides at particular regions on a single DNA strand are replaced by new ones using a DNA polymerase. The replacement nucleotides are then utilized to incorporate fluorophores into the DNA strand and allow for visualization. Nicking enzymes and methyl-transferases present two different approaches to employ enzymatic labelling process. While the use of differently colored fluorophores extends the applicability of this technique, the final resolution depends on the degree of stretching and the density of fluorophores on the region.

Affinity-based labelling is based on non-covalent interactions which can be enabled by either denaturation mapping or competitive binding. In denaturation mapping, DNA is heated to discriminate between the bases by their different bond energies. While G-C-basepairs still hold both strands of DNA—due to 3 hydrogen bonds holding them—, A-T-basepairs will melt—due to 2 hydrogen bonds holding them—. At this stage, an intercalating fluorescent dye can be linked to G-C-basepairs, allowing for imaging. Competitive binding relies on the usage of a fluorescent intercalating dye and a molecule selective for either A-T or G-C regions. Therefore, fluorescent dye cannot bind where the selective molecules have already bound. An optical map of DNA molecules can be obtained in this way. Affinity-based labelling is also highly dependent on the degree of stretching.


Optical DNA mapping techniques are useful tools for a wide range of applications from assembly of complex genomes to bacterial plasmid epidemiology. The concept opens up exciting research directions as it allows for automation of whole analysis using lab-on-a-chip systems and observation of the results using smartphones.

optical DNA mapping

Figure 1. Schematic illustration of DNA labelling techniques used in optical DNA mapping. Enzyme-based labelling involves nicking enzymes and methyl-transferases techniques, while affinity-based labelling can be employed by denaturation mapping or competitive binding methods. This figure is adapted from “Optical DNA mapping in nanofluidic devices: principles and applications” paper.

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

Optical DNA mapping in nanofluidic devices: principles and applications

Vilhelm Müller and Fredrik Westerlund

Lab Chip, 2017, Articles

DOI: 10.1039/C6LC01439A

 

*Free to access until 5th May 2017.


About the Webwriter

Burcu Gumuscu is a postdoctoral fellow in BIOS Lab on a Chip Group at University of Twente in The Netherlands. Her research interests include development of microfluidic devices for next generation sequencing, compartmentalized organ-on-chip studies, and desalination of water on the microscale.

 

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Recent Advances in 3D Printing

Guest edited by Jennifer Lewis (Harvard University) and Howard Stone (Princeton University) this collection of papers showcases recent advances in the rapidly evolving field of 3D printing, with an emphasis on themes that impact lab-on-a-chip applications.

Free* Access: The upcoming 3D-printing revolution in microfluidics
Critical Review
Nirveek Bhattacharjee, Arturo Urrios, Shawn Kang and Albert Folch
Lab Chip, 2016,16, 1720-1742 DOI: 10.1039/C6LC00163G

Free* Access: High density 3D printed microfluidic valves, pumps and multiplexers
HOT Article
Hua Gong, Adam Trticle. Woolley and Gregory P. Nordin
Lab Chip, 2016,16, 2450-2458 DOI: 10.1039/C6LC00565A

Free* Access: Bioprinted Thrombosis-on-a-Chip
HOT Article
Rahmi Oklu et al.
Lab Chip, 2016, Accepted Manuscript, C6LC00380J

Open Access: 3D- printed microfluidic devices: enablers and barriers
Michael C. Breadmore., et al
Lab Chip, 2016,16, 1993-2013
DOI: 10.1039/C6LC00284F

This collection also features a video demonstration:

3D printing of liquid metals as fugitive inks for fabrication of 3D microfluidic channels
Dishit P. Parekh, Collin Ladd, Lazar Panich, Khalil Moussa and Michael D. Dickey
Lab Chip, 2016,16, 1812-1820 DOI: 10.1039/C6LC00198J

Browse our 3D Printing collection – we hope you enjoy the articles

*Access is free until 10th October via a registered RSC account.

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A new challenge for children: getting rid of pathogens from water using microfluidics

The use of microfluidics to test the safety of drinking water is growing increasingly. Although several microfluidic concepts are already shown to detect pathogens in water useful for this industry, the authors of this article focus on the use of such a device for a different audience: young children.  They show that it can be perfectly used as an educational tool to make children more aware of the importance of clean water and the advantages of microfluidics.

In total six modules are developed, each of them having own teaching objectives and materials. The modules can be used separately and both standardized techniques as well as new microfluidic techniques are treated. For instance the use of the microfluidic separation technique deterministic lateral displacement to separate pathogens out of the water is visualized on a macroscale using LEGO® and particles made with FIMO® clay. The good particles are smaller in diameter than the bad ones, making separation in on macroscale using viscous media (in this case shower gel) possible.

A complete activity is made by the authors, that shows a new and original approach to make young children aware of the challenges in science, technology, engineering and mathematics. By using simple components in combination with cartoons and descriptions, the child can remove the bad pathogens from drinking water in about 30 minutes.

For more information, download the full article now – access is free* for a limited time only!

Angry Pathogens, how to get rid of them: introducing microfluidics for waterborne pathogen separation to children
Melanie Jimenez and Helen L.Bridle
DOI: 10.1039/C4LC0944D

* Access is free through a registered RSC account until 23rd January 2015.

About the webwriter

Dr Loes Segerink is an Assistant Professor in the BIOS Lab-on-a-Chip Group at the University of Twente. Read more about her research interests on her homepage.

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Engineering the ‘microHuman’

Research based on the use of organs-on-chips is rapidly expanding and developing. These microengineered devices are microfluidic physiological models of tissues and organs. All sorts of organs-on-chips have been reported, including lung-on-a-chip, heart-on-a-chip and even blood-brain barrier-on-a-chip. See http://dx.doi.org/10.1039/C2LC40089H for a Frontier article by Ingber et. al., which focuses on advances in these microengineered organs.

The models have great potential in the field of pharmacology and toxicology, where they can be used to chart the effects of candidate drugs. But what if we could connect all these organs-on-chips together, and create an actual ‘human-on-a-chip’? Could such a model be used to replace the popular animal models? Could we soon be testing our drug candidates not on mouse or rat, but on the microHuman?

What would a microHuman look like? The answer is tiny. It would be a million times lighter than a regular human, giving it a mass of merely 70 mg. At such an incredible size, would the microHuman be functional, like you or I?

In a Critical Review by John Wikswo and colleagues (http://dx.doi.org/10.1039/C3LC50243K), the scaling requirements of a microHuman are discussed. It is concluded that a simple scaling system is not enough; a microhuman would be completely dysfunctional if we applied basic scaling laws to it. For example, its breathing rate would be approximately 10 breaths per second. In addition, its capillaries would be so small that any naturally-occurring blood cell would be too large to traverse them.

In response to these barriers, Wikswo and colleagues provide detailed discussion of scaling in a number of organ systems in the microHuman. Additionally, they give an overview of structural and functional parameters to guide the scaling of organs-on-chips in a microHuman, which are based upon human and animal data.

Interestingly, whilst the potential of a microengineered human-on-a-chip is huge, Wikswo et. al. point out that, like any model system, the microHuman will never be perfect: “It is important to realize that [these] systems reside in a niche of abstraction that will improve constantly with technology but will never exactly recreate a full human, which represents approx. 109 years of evolutionary engineering”.

Organs-on-chips, and their potential for the development into humans-on-chips, are currently an incredibly hot topic area. If you want to find out more, in addition to Wikswo’s excellent review you can read more about this exciting field in a paper by Shuichi Takayama and colleagues, published recently in the RSC Journal Integrative Biology (http://dx.doi.org/10.1039/C3IB40040A).

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LOC issue 4 – the Neuroengineering 2013 themed issue is online now!

                                                         

Lab on a Chip’s 2013 Neuroengineering themed issue is introduced by guest editors David T. Eddington and Justin Williams, who also contributed the outside front cover design. This is followed by profiles of all of the contributors to the Neuroengineering themed issue.

Neuroengineering
David T. Eddington and Justin Williams
DOI: 10.1039/C3LC90003G

 

As well as plenty of cutting-edge primary research into lab on a chip technology for neuroengineering, Issue 4 includes two Critical Reviews.

A critical review of the development of engineered cell culture substrates and techniques for investigating axon development guidance by Santiago Costantino et al. at University of Montreal and McGill University, Canada, is highlighted on the inside front cover. They look at the opportunities that are now opening up due to these new technological developments, the biological insights that can now be gained and the breakthroughs waiting to happen in the near future.

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

 

The second critical review from Noo Li Jeon et al. at Seoul National University, Korea, and The Salk Institute, USA, summarises the most recent technological developments of BioMEMs devices and their application to neuroscience research. They look at platforms for disease culture, modelling disease in vitro, neuron electrophysiology and stem cell biology.

Advances in microfluidics-based experimental methods for neuroscience research
Jae Woo Park, Hyung Joon Kim, Myeong Woo Kang and Noo Li Jeon
DOI: 10.1039/C2LC41081H

 

The HOT articles in this issue include:

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 Taylor
DOI: 10.1039/C2LC40954B

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

One-step polymer surface modification for minimizing drug, protein, and DNA adsorption in microanalytical systems
Esben Kjær Unmack Larsen and Niels B. Larsen
DOI: 10.1039/C2LC40750G

 

To learn all about the exciting advances happening in applying microtechnology to neuroengineering, read the full issue here

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Focus on circulating tumor cells in microfluidics

This important Focus article looks at the most up to date research on the isolation and characterisation of circulating tumor cells (CTCs) using microfluidic techniques.

CTCs are produced when tumor cells break off and enter the circulatory system. This makes them important targets for diagnosis and monitoring. However they are only present in extremely small quantities in the blood, meaning plenty of technical difficulties arise when trying to accurately characterise and assess them in a blood sample.

This Focus highlights: 

  1. Considerations in design of CTC isolation, separation and detection systems
  2. Disadvantages of macroscale systems
  3. Magnetic-based microfluidic systems
  4. Affinity chromatography-based microfluidic systems
  5. Size and deformability-based microdevices
  6. Dielectrophoretic-based microdevices

Tony Jun Huang et al. based at The Pennsylvania State University, Massachusetts Institute of Technology (MIT) and Harvard Medical School, USA, finish by discussing the possible combination of the above systems and the future of such technology in terms of clinical relevance for different cancers and technological development.

We’ve made this article free to access for the next 4 weeks*, read it now by clicking the link below:

Probing circulating tumor cells in microfluidics
Peng Li, Zackary S. Stratton, Ming Dao, Jerome Ritz and Tony Jun Huang
DOI: 10.1039/C2LC90148J

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

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