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Multifunctional optofluidic lab-on-chip platform for Raman and fluorescence spectroscopic microfluidic analysis

 
An automated optofluidic biosensor platform combining interferometric sensors and injection moulded microfluidics

 

Characterisation of anticancer peptides at the single-cell level

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3D Printing Truly Micro Microchannels

Written by Darius Rackus, postdoctoral researcher at University of Toronto

A new 3D printer and resin formula enable 3D printing of channels on the microscale

 

There is no doubt that 3D printing is a hot technology with applications across all sectors of industry and life. The technology is attractive not only for its use in rapid prototyping, but also for its ability to form complex structures that could not easily be formed by other manufacturing techniques. There is also the added benefit of digital design—it is very easy to go from a CAD model to physical production without the need of additional tooling or equipment. For these reasons and others, 3D printing is an attractive manufacturing process for microfluidics.

Albert Folch has argued that 3D printing is the solution to the barriers preventing the translation of PDMS microfluidics to commercial applications. (Angew. Chem. Int. Ed. 2016, 55, 3862–3881.) However, printing resolution has limited the size of channels to the milli- and sub-millifluidic regimes. The challenge when it comes to microchannels is that commercial 3D printers are designed to form polymer features but microchannels, by their nature, are voids within bulk material. While many 3D printer manufacturers tout resolutions in the tens of micrometers, the reality is that the resolution of the void spaces can be several-fold larger. In their recent report, researchers at Brigham Young University have advanced 3D printing technology to print channels truly in the micro- regime.

 

Left: Schematic illustration of 3D stacked serpentine channel design. Right: SEM image of 3D serpentine channel cross section.

Achieving true micro-scale printing resolution required innovation in both the 3D printer and the resin material. Gong et al. modified a digital light processing (DLP)-type 3D printer to include a high resolution light engine and a 385 nm UV LED light source. DLP printers project a pattern of light over the entire plane, crosslinking an entire layer in a single step. The light engine enables resolutions in the x-y plane of 7.6 µm and their choice of a 385 nm light source opened a wide range of possible UV-absorbers to them. Twenty different UV-absorbers were evaluated and 2-nitrophenyl phenyl sulfide (NPS) was chosen as having all the desired properties, with the main criterion of enabling smaller void sizes in the z-dimension. The final composition of the resin was a mixture of poly(ethylene glycol) diacrylate (PEGDA), NPS, and Irgacure 819. This mixture created structures that have low non-specific adsorption and had good resolution in the z-axis. Additionally, the structures could be photocured with a broad-spectrum UV lamp after printing.

Despite high-resolution printers and materials, a new printing regime also had to be developed to achieve the desired channel width. Because of scattering, the area of crosslinked resin tended to be smaller than the actual pixel size. This meant that channels, which are essentially voids of non-exposed space, came out wider than designed. The solution that Gong et al. devised was to perform two print patterns for each exposed layer. The first print pattern exposes the entire area, save for the channel void and the second exposure only projects a pattern along the channel walls. This method enabled reproducible printing of channels with a ~20 µm width.

3D CAD model of the custom 3D printer by Gong et al.

 

So how soon can you expect to get your hands on a 3D printer capable of printing true microchannels? While this report has been very promising, it is currently the only printer and only resin formulation with these capabilities. According to Greg Nordin, the corresponding author, the main challenge is to figure out “how to get this into people’s hands in a convenient way so they don’t have to mess around much to get it to work.” Like any new technology, for it to be truly useful, users want to spend more time making and less time fiddling. Fortunately, there already are markets for printing small, intricate parts, such as jewelry and dentistry, so it’s only a matter of time before manufacturers catch on to the market for 3D printed microfluidics.

 

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

Custom 3D printer and resin for 18 μm × 20 μm microfluidic flow channels
Hua Gong, Bryce P. Bickham, Adam T. Woolley and Gregory P. Nordin
Lab Chip, 2017
DOI: 10.1039/C7LC00644F

*Free to access until 29th August 2017.


About the Webwriter

Darius Rackus is a postdoctoral researcher at the University of Toronto working in the Wheeler Lab. His research interests are in combining sensors with digital microfluidics for healthcare applications.”

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TISuMR 1: Symposium On Tissue Culture and Magnetic Resonance

The first TISuMR Symposium on Tissue Culture and Magnetic Resonance will take place from 24th – 27th September2017, in WinchesterUK.

The culture of tissue under controlled conditions holds great promise for the future of medicine and the life sciences in general. While the study of cells provides detailed insight into biological processes at the molecular and supra-molecular scale, understanding many disease processes requires a more systemic approach.

Culture of  tissues, either from organ samples or grown entirely in vitro, can provide insight at the organ system level, revealing not only the function of individual cell types, but also their interaction with each other as well as with the extracellular matrix.

Combining advanced microfluidic lab-on-a-chip approaches to tissue culture with non-invasive, in-situ NMR investigation of life processes is the central theme of the TISuMR project. This symposium will bring together clinical experts on liver pathology,  researchers working on microfluidic tissue culture,  and scientists developing novel magnetic resonance techniques, with the following aims:

  • Exchange ideas across discipline boundaries.
  • Discuss opportunities and challenges in the field.
  • Establish the potential of the TISuMR approach for developing liver disease models.
  • Foster mutual understanding between the biomedical and technical aspects of the project.

The technical program will feature a number of leading scientists in the fields of hepatology, microfluidic technology, and magnetic resonance as keynote speakers. In addition, members of the TISuMR team will present their projects and early results.

Register here for the conference

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How can biosensors provide real-time health monitoring?

Like a ripple spreading outwards on a pond’s surface, a plasmon is a collective oscillation of free electrons in a piece of metal. When the metal interacts with light (in this case k vector of light satisfies the momentum condition), the collective movement of oscillating electrons at the metal’s surface leads to the propagation of the light along the surface, also known as a surface plasmon. This simple physics rule is very helpful for sensor nanotechnology and optical signal processing applications since the offered advantages are significant, providing a smaller foot-print, lower limits of detection, and multiplexing opportunities. However, using sensors for biomolecule detection requires clever use of light. For example, surface plasmon resonance can be observed in nanohole arrays patterned on very thin gold films. Nanohole arrays can transmit light much more strongly than expected for the nanohole apertures at certain wavelengths. This phenomenon is called extraordinary optical transmission (EOT) and opens a new avenue for detection of minute amounts of biomolecules.

A nanoplasmonic biosensor was recently developed for real-time monitoring of proteins from live cells in a label-free configuration, thanks to extraordinary optical transmission. The biosensor is structured in a microfluidic device consisting of a cell module and the biosensor module. Microfluidic cell module design is based on a single zigzag channel for directly delivering the secreted proteins to the adjacent biosensor module via a tubing connection. The biosensor module consists of nanoholes fabricated on freestanding SiNx membranes. Antibodies specific to vascular endothelial growth factor (VEGF) are selectively immobilized on the gold nanohole arrays as biorecognition molecules. When the VEGF are captured on the sensor, a change of refractive index proximate to the surface is induced. This change results in a peak shift of the EOT spectrum (Figure 1). By tracing the spectral shifts continuously, the dynamics of cell secretion can be monitored. In this way, the secretion dynamics from live cancer cells are monitored and quantified for 10 hours. The proposed microfluidic device has unique capabilities for multiplexed and label-free detection in a compact footprint, which are promising for miniaturization and integration into lab-on-a-chip devices.

biosensor, microfluidics, extraordinary transmission phenomena, nanohole arrays

Design and working principle of microfluidic-integrated biosensor. Cancer cells grow in a zigzag channel, and secreted vascular endothelial growth factor are directly delivered to the adjacent detection module. Nanohole structures fabricated in the detection (biosensor) module are shown in SEM image with a scale bar of 1 μm (bottom left). The images on the right show the characteristic resonance peak (solid line) and EOT spectral shift of the peak upon binding (dashed line). Spectral displacements of the resonance peak based on molecular binding accumulation is shown in the sensorgram to reveal the real-time binding dynamics. Adapted from Li et al. (Lab Chip, 2017).

This technology will have a potentially significant impact on medicine. Most of the patients agree that preventive medicine is preferable to reactive medicine. However, preventive medicine requires frequent physical exams, which can only be maintained by spending substantial time and money at physicians’ offices. The need for frequent check-up exams could be reduced or eliminated by real-time monitoring of the health status by portable biosensors in the future. Developing biosensors that allow real-time monitoring of target biomolecules is a big step towards the addressing this future goal.

 

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

Plasmonic nanohole array biosensor for label-free and real-time analysis of live cell secretion

Xiaokang Li, Maria Soler, Cenk I. Özdemir, Alexander Belushkin, Filiz Yesilköy and Hatice Altug

Lab Chip, 2017

DOI: 10.1039/C7LC00277G

 

*Free to access until 7th August 2017.


About the Webwriter

Burcu Gumuscu is a postdoctoral fellow in Herr Lab at UC Berkeley in the United States. Her research interests include development of microfluidic devices for quantitative analysis of proteins from single-cells, next generation sequencing, compartmentalized organ-on-chip studies, and desalination of water on the microscale.

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Droplet-Based Single-Cell Sequencing

We are pleased to announce the latest Thematic Collection in Lab on a ChipDroplet-Based Single-Cell Sequencing!

We are delighted that Lab on a Chip Advisory Board member David A Weitz (Harvard University, USA) is Thought Leader of this collection!

The field of droplet-based single-cell sequencing field has made increasing advances in recent years. Large numbers of studies are underway to collect and explore the new information that is now accessible with single-cell RNA-seq. Improvements to microfluidics are advancing rapidly and extensions to other sequencing methods are also being developed, enabling investigations to probe information beyond mRNA alone. This has rapidly become a burgeoning field, where microfluidic techniques are essential and where droplet-based microfluidics has enabled a major advance.

For more context, please read the editorials “Perspective on droplet-based-single cell sequencing” by David Weitz and “InDrops and Drop-seq technologies for single-cell sequencing” by Allon Klein and Evan Macosko.

The goal of this collection is to highlight the new advances in this growing field, with an emphasis on the interface between the technological advancements and high impact applications of droplet-based single-cell sequencing.

Interested in submitting to the collection?

If you are interested in contributing to the droplet-based single-cell sequencing collection, please get in touch with the Lab on a Chip Editorial Office at loc-rsc@rsc.org and provide a title and abstract of your proposed submission.

Articles will be published as they are accepted and collated into an online Thematic Collection, which will receive extensive promotion.

Submissions for this collection are open from 15th July 2017 to 30th April 2018 

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New YouTube Videos

Automated and controlled mechanical stimulation and functional imaging in vivo in C. elegans

 
On-chip cell sorting by high-speed local-flow control using dual membrane pumps

 
Photoelectrochemical ion concentration polarization: membraneless ion filtration based on light-driven electrochemical reactions

 

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Meet our new Advisory Board members!

Oscar Ces is a Professor in Chemistry at Imperial College London, UK. He is a leading specialist in soft condensed matter, chemical biology, microfluidics, artificial cells, single cell analysis and lipid membrane mechanics.
 Daniel Irimia is an Associate Professor of Surgery and Deputy Director of the BioMEMS Resource Center at the Center for Engineering in Medicine (CEM) at Massachusetts General Hospital, USA. He is an internationally recognized expert in bioengineered microsystems for cellular chemotaxis and other functional assays.
  Sunghoon Kwon is an Associate Professor in the Department of Electrical and Computer Engineering at Seoul National University, South Korea. His research interests include optofluidic nanofabrication, BioMEMS, bioengineering, biophotonics, ultrasmall laser projection display, and human computer interfaces.
   Weihua Li is a Senior Professor for the School of Mechanical, Materials and Mechatronic Engineering at Wollongong University, Australia. His research focuses on magnetorheological (MR) fluids and MR elastomers and their applications, dynamics and vibration control, microfluidics and nanofluidics and lab on a chip.
  Chwee Teck Lim is a NUSS professor in the Department of Biomedical Engineering at the National University of Singapore. His research focuses on human disease biomechanics & mechanobiology, microfluidic technologies for disease detection, diagnosis and therapy and 2D materials for biomedical applications.
Nam-Trung Nguyen is Director of the Queensland Micro- and Nanotechnology Centre at Griffith University, Australia. His research is focused on microfluidics, nanofluidics, micro/nanomachining technologies, micro/nanoscale science, and instrumentation for biomedical applications.
David Sinton is a Professor and Canada Research Chair in Microfluidics and Energy at the University of Toronto. His research involves the study and application of small scale fluid mechanics (microfluidics, nanofluidics, and optofluidics) for use in energy systems and analysis.
  Hongkai Wu is Associate Professor for the Microfluidics Group at the Hong Kong University of Science and Technology. His research focuses on the interdisciplinary frontiers of microfluidics, bioanalytical science and materials chemistry.
  Chaoyong James Yang is a Professor in Chemical Biology at Xaimen University, China. His current research centers on microfluidics, molecular recognitions, DNA self-assembly and early diagnosis of cancer.
  Roland Zengerle is the Head of Laboratory for MEMS Applications and co-director of Hahn-Schickard at the University of Freiburg, Germany. He specializes in lab-on-a-chip systems, contact-free microdosage technologies and applications, miniaturized and implantable drug delivery systems, analysis and modeling of porous electrodes in batteries and fuel cells and biofuel cells.
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New YouTube Videos

Size-Tunable Microvortex Capture of Rare Cells

 
Droplet-based light-sheet fluorescent microscopy for high-throughput sample preparation, 3-D imaging and quantitative analysis on a chip

 
Organs-on-Chips with combined multi-electrode array and transepithelial electrical resistance measurement capabilities

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Organ-, Body- and Disease-on-a-Chip Thematic Collection

We are pleased to announce Lab on a Chip‘s first Thematic Collection in 2017, Organ-, Body- and Disease-on-a-Chip!

We are delighted to announce that Michael Shuler (Cornell University, USA) will be acting as Thought Leader for this collection. His research focuses on “Body-on-a-Chip” devices applied to evaluate different treatments for cancer, such as multi-drug resistant cancer. Read Michael Shuler’s recent Editorial for more information.

An emerging area of interest for drug development over the last 13 years has been constructing human biomimetic systems by combining the techniques of microfabrication and tissue engineering. In this collection, we define an “Organ-on-a-Chip” as a physical microscale model (typically an order of 10−6 to 10−4 of actual size) of a particular human organ.

The questions we aim to address in this collection are whether these emerging technologies will improve both drug development and the regulation of human exposure to chemicals. What technical challenges remain? What will be the most effective way to utilize this emerging technology? Can this technology lead to cost effective, measurable improvements in human health? Our goal is to highlight the new advances in this growing field with an emphasis on the interface between the technological advancements and high impact applications of organ-, body- and disease-on-a-chip technologies.

Interested in submitting to the collection? 

If you are interested in submitting to the series, please get in touch with the Lab on a Chip Editorial Office at loc-rsc@rsc.org and and provide a title and abstract of your proposed submission.

Articles will be published as they are accepted and collated into an online Thematic Collection, which will receive extensive promotion. Read the collection so far – rsc.li/organonachip

Submissions to this collection are open between 1st July 2017 and 31st March 2018

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New YouTube Videos

A Versatile Microfluidic Device for High Throughput Production of Microparticles and Cell Microencapsulation

 
Universal signal generator for dynamic cell stimulation

 

Deterministic trapping, encapsulation and retrieval of single-cells

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