Archive for the ‘Hot Articles’ Category

Digital Whispers: Novel optical sensors enable label-free sensing with digital microfluidics

If you’ve ever visited St. Paul’s Cathedral in London or Grand Central Terminal in New York, you may be familiar with the interesting acoustic phenomenon termed a “whispering gallery”. The domed geometry of these structures allows sound to echo around the chambers such that a whisper spoken along the wall on one side can be clearly heard at the other end. This phenomenon can also apply to light, and microstructures tuned to a specific wavelength of light can be used as resonating sensors. Whispering-gallery mode (WGM) micro-goblet lasers use this phenomenon and can detect changes in the refractive index of the surrounding media as well as changes to the surface. This makes them ideal as label-free sensors that can detect changes to the surfaces of the microgoblets. When their surfaces are functionalized with capture moieties (e.g., antibodies, nucleic acids etc.) they can be used for sensitive label-free detection and would be a great tool to incorporate with microfluidics.

In their recent report, Wondimu et al. integrated arrays totaling 5,000 individually addressable sensors with a digital microfluidic (DMF) chip. DMF offers precise handling of nL-µL volume droplets in a compact format and with no moving parts. Typically, WGM sensors require coupling to fiber optics, but by doping the micro-goblets with organic dyes they can be operated as optically pumped lasers. This makes operating them less bulky and fits well with the streamlined philosophy behind DMF (i.e., no pumps, tubing, or connections). The fabrication of these large arrays is simple and relies on wet-etching and reflowing. Thus, scale-up is relatively straightforward. In their report, Wondimu et al. demonstrated the functionality of these sensors by testing liquids with different refractive indices as well as performing quantitative detection of streptavidin-biotin binding on the sensor surfaces. While these examples serve a demonstrative purpose, it will be possible to use these sensors for multiplexed affinity-based biosensing such as antibodies, nucleic acids, and aptamers. This will be a big leap for DMF as there haven’t been any examples of integrated multiplexed sensing on this scale before. One area where this could be applied to is the development of platforms to culture cells and perform multiplexed, label-free genetic analysis—a true micro total analysis system!

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


Integration of digital microfluidics with whispering-gallery mode sensors for label-free detection of biomolecules
Sentayehu F. Wondimu, Sebastian von der Ecken, Ralf Ahrens, Wolfgang Freude, Andreas E. Guber and Christian Koos
Lab Chip, 2017
DOI: 10.1039/C6LC01556E

*Free to access until 6th June 2017.


About the Webwriter

Darius Rackus is finishing his Ph.D. 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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Game on!

Researchers at Standford University develop multi-level programming language for biotic games using swarms of microorganisms

Computer games are a ubiquitous pastime and a great example of how a single programming language give rise to a myriad of games. But what about biotic games? How could you program biological systems to function in an interactive way? Biotic games are interactive applications that interface biology and computer science for the promotion of science. The Riedel-Kruse Lab at Standford specialize in developing biotic games that use light to control swarms of Euglena gracilis—a phototaxic microorganism that avoids—and can direct, capture, and move whole swarms or individual organisms.

But programming swarms of microorganisms is no easy task. Swarms exhibit collective behaviour and therefore need to be controlled through local context rather than at the individual level. In their recent publication, the Riedel-Kruse Lab developed a set of hierarchical programming abstractions that allows swarms of Euglena within a biological processing unit (BPU; i.e., chip, microscope, and light stimuli) to be programmed in a single and efficient language at the stimulus, swarm, and system levels. At the lowest level, stimulus space programming (which the authors analogize to machine code) allows the programmer to have direct control over the various stimuli (e.g., turn left light on for 3 s), independent of the Euglena. Higher level programming at the swarm and system levels are more general and commands are given in terms of what the user wants the Euglena or system to do. For instance, swarm space commands direct the swarm in different operations such as move, split, and combine. System space commands incorporate conditional statements that can be used to confine a specific number of Euglena to a certain region or to clear Euglena from the field of view, for example.

 

 

While Lam et al. used this new language to program a biotic game, this new language and approach to swarm programming could be generalized for any type of swarm and stimuli. One application could be to program swarms to construct complex structures on the microscale. In future, by increasing access to BPUs through cloud computing and releasing this new programming language it will be possible for hobbyists and researchers alike to write new programs and applications. And maybe this is just the beginning of a revolution like the one ushered in by the release of the personal microcomputer.

 

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

Device and programming abstractions for spatiotemporal control of active micro-particle swarms

Amy T. Lam, Karina G. Samuel-Gama, Jonathan Griffin, Matthew Loeun, Lukas C. Gerber, Zahid Hossain, Nate J. Cira, Seung Ah Lee and Ingmar H. Riedel-Kruse

Lab Chip, 2017,17, 1442-1451

DOI: 10.1039/C7LC00131B

 

*Free to access until 24th May 2017.

 


About the Webwriter

Darius Rackus is finishing his Ph.D. 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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Sample-in-answer-out

You have worked hard all year and wanted to treat yourself with something different for the summer. You decided to arrange a journey to South-Africa to enjoy the beautiful natural scenery. Discovering the range of wildlife in immense national parks, hiking in mountains, and meeting with warm locals made your journey unforgettable. You arrived at one of the best photography spots in a national park just before the sunset. While focussing on capturing the best image from the picturesque scenery, you got bitten by a Marsh mosquito, perhaps infected with a Plasmodium falciparum parasite. This parasite is known for causing malaria, the most significant parasitic disease of humans. You are not the only one: approximately 30,000 travellers from industrialized countries contract malaria each year. During the next 14 days, this parasite will differentiate and proliferate in the body. It will invade and destroy the red blood cells, eventually affecting the liver, spleen, and brain functionality. A few days after the bite, you found a small-scale laboratory for the malaria diagnosis test, but there was a problem: this laboratory can detect malaria only if you have 50-100 parasites per microliter of blood, occurring when the patient carries the parasite for weeks. You, then, had to find a larger laboratory equipped with a benchtop loop-mediated isothermal DNA amplification (LAMP) system, which can detect 1 malaria parasite per microlitre of blood. You wished there was a highly sensitive device for malaria diagnosis at the point of need. Well, we might have some good news for you.

Modern nucleic acid testing methods of malaria detection, such as LAMP, enable high sensitivity, high specificity, robust, and rapid analyses for asymptomatic infections. As performing these methods requires bulky and costly peripheral equipment and trained technicians, access to such equipment in rural areas is unlikely. Fortunately, researchers in Pennsylvania State University recently introduced a stand-alone, portable, and high sensitivity system that can perform “sample-in-answer-out” analyses. The system consists of a compact disc and a reader unit (Figure 1). The compact disc includes valves and microfluidic channels, where the blood sample is processed using magnetic beads. The reader unit can automatically perform all analysis steps including DNA purification, elution, amplification, and real-time detection. For a real demonstration of how the test is performed, the movie included below is well worth the watch. Test results can be displayed on a LCD screen or a smartphone within 40 minutes. The system can detect down to 0.6 parasites per microliter of blood. Each test costs around $1. With these specifications, this technology has the opportunity to create a new paradigm in molecular diagnosis at the point of care.

malaria detection test

Figure 1. Schematic view of an assembled compact disc made of PMMA; AnyMDX reading unit consisting of a magnet, heater plate, optical detection system, and LCD screen; and the illustration of integrated sample processing steps on the compact disc. The technique is based on DNA-carrying magnetic beads actuated against stationary reagent droplets.

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

A field-deployable mobile molecular diagnostic system for malaria at the point of need

Gihoon Choi, Daniel Song, Sony Shrestha, Jun Miao, Liwang Cuic and Weihua Guan

Lab Chip, 2016, Articles

DOI: 10.1039/C6LC01078D

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 includedevelopment of microfluidic devices for next generation sequencing, compartmentalized organ-on-chip studies, and desalination of water on the microscale.

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What can a magnet do?

The magic of magnetism can be shown through a simple classroom demonstration of bringing two magnetic pieces together and then trying to pull them apart. The attraction between the opposite poles of the magnets becomes very apparent as you struggle to tear them apart. This simple concept can be applied to lab-on-a-chip devices to eliminate the need for off-device hardware with power requirements, and therefore, enable the use of lab-on-a-chip technology in low-resource settings.

The majority of existing lab-on-a-chip systems use manual pipettes, syringe pumps, or pressure pump systems to manipulate the fluid flow. The dependence on off-chip hardware, however, makes the integration of these systems into low-cost environments rather challenging. Researchers in both, academia and industry think that this challenge can be addressed by “manually operated self-contained microfluidic devices”, which has gained significant attention over the past couple of years. In line with this objective, magnetically-adhesive based valves have for the first time shown to control fluid flow in a microfluidic device in a recent collaboration work by Sandia National Labs and Qorvo Inc. Here, the “magnetic-adhesive based valve” simply consists of a disk magnet seated on a thin ring of adhesive material.

In this study, a microfluidic device is designed to perform bioassays and contains a port connecting two chambers in different planes. The port is closed by an internal magnet located on a pressure-sensitive adhesive tape, and is opened by the help of an external magnet which displaces the internal magnet (figure 1). When the port is open, the reagents can flow in the microchannels, as shown in figure 2. The adhesive tape prevents any leakage within the microchip, while the magnet serves as an actuatable gate for reagents. The microfluidic device, therefore, allows for storage and on-demand transport of different types of reagents (both liquid, solid, and gas) to perform bioassays.

Magnetic-adhesive based valves are fabricated at the millimeter-scale, however, it is possible to manufacture micron-sized valves depending on the resolution of the laser ablation system used to cut the valve layout. Design considerations and characterization of magnetic-adhesive based valves are further addressed in the paper. Apart from this, the self-contained device is made of low-cost materials (such as PMMA and magnetic alloys), resulting in a fabrication cost as low as 0.2 dollars per chip. As portable and low-cost devices start to draw increasing attention in lab-on-a-chip technology, this work might be an important milestone for next generation micro total analysis systems.

Magnetic valves for lab on a chip sytems

Figure 1. Schematic and photos of magnetic-adhesive based valve working mechanism.

Magnetic valves for lab on a chip devices

Figure 2. Controlled transport and reaction of the stored components in a simple, power- and instrument-free manner in a three chambered microfluidic device.

This is a recently published Hot article and you can download it for free* by clicking the link below:

Magnetic-adhesive based valves for microfluidic devices used in low-resource settings

Jason C. Harper, Jenna M. Andrews, Candice Ben, Andrew C. Hunt, Jaclyn K. Murton, Bryan D. Carson, George D. Bachand, Julie A. Lovchik, William D. Arndt, Melissa R. Finley and Thayne L. Edwards

Lab Chip, 2016, Recent HOT Articles

DOI: 10.1039/C6LC00858E


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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Blood matters

Iron deficiency anemia (IDA) is not a trivial illness. Every individual in the world’s population has the potential to suffer from this nutritional disease. According to estimations, 900 million people worldwide are already afflicted with it. IDA is known to lower cognitive ability, work capacity, and future productivity of both children and adults. The situation appears to be grave when we consider the economic consequences of these problems.

The human body needs iron to produce red blood cells, and having low iron levels in the body leads to IDA. Diagnosis of IDA requires a complete blood count is performed by a bulky hematology analyzer. IDA has been a common disease for a really long time; however, its associated diagnosis costs are considerably high, and the diagnosis equipment is not available in many places of the world. Given the facts, IDA diagnosis actually deserves cheaper and easily accessible equipment, which has unfortunately remained elusive—up until now.

In last month’s issue of Lab on a Chip, Whitesides research group at Harvard University came up with a sound idea to diagnose IDA in a shorter and inexpensive way. They developed a low-cost and rapid-screening tool to diagnose IDA using aqueous multiphase systems containing layer of polymer-salt mixtures. These mixtures are loaded in a microhematocrit tube (depicted in the figure) together with a drop of blood from a fingerprick. Diagnosis results become available after a 2-minute low-cost centrifuging process.

The reported data suggest that diagnosis of IDA is improved by means of sensitivity and specificity when compared to the bulky hematology analyzer’s results. Several important red blood cell parameters, such as concentration of hemoglobin in a given volume of red blood cells, can be predicted. The technique’s ability to diagnose IDA was further improved using automated digital analysis. They also show that the tool is able to detect a wider range of anemia types including microcytic and hypochromic anemia. The portable and low cost screening tool could possibly find use in rural clinics where large fractions of the population at risk of IDA. Before entering the market, the performance of this technique will still have to be validated to demonstrate feasibility of using and interpreting the assay.

Design of the presented test loaded with blood before and after centrifugation for a representative IDA and Normal sample. Blood is loaded into the top of the tube, from a fingerprick, using capillary action provided by a hole in the side of the tube. Normal blood packs at the bottom of the tube, while less dense blood cells can be seen packing at the interfaces between the phases and inside the tube. Normal and IDA blood can be differentiated by eye after only 2 minutes of centrifugation. It is also possible to read the analysis results in an automated way. A commonly used software is used to convert the image to red intensity graphs.

This article was published in Lab on a Chip on 30th August 2016.

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

Diagnosis of iron deficiency anemia using density-based fractionation of red blood cells

Jonathan W. Hennek, Ashok A. Kumar, Alex B. Wiltschko, Matthew R. Patton, Si Yi Ryan Lee, Carlo Brugnara, Ryan P. Adams and George M. Whitesides
Lab Chip, 2016,16, 3929-3939
DOI: 10.1039/C6LC00875E

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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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*Access is free until 7th November 2016 through a registered RSC account – register here

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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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Chlorophyll lasers

From space shuttles to military equipment, or even the kitchenware that we use on daily basis, lasers have found use in more places than we often realise. Interestingly, the solid-state lasers were believed to be a solution to an unknown problem after their invention in 1950s. In that time nobody—including their developer Charles Townes—noticed that the lasers were one of the game changer inventions in the world’s history. After tens of years, in 1964, the laser technology was awarded with a Nobel prize when its potential for diverse applications were realized.

So far we have only discussed solid-state lasers, but there is definitely capacity in the laser world to improve the performance and versatility with the help of little twists, such as optofluidic lasers. “Optofluidics” is a synergic combination of optical systems and microfluidics. In other words, optical systems are built or synthesized from liquids, aiming to serve as good as their solid-state equivalents. For example, two immiscible liquids form a smooth surface in their interface, leading to a laser cavity or an optical resonator with a very high Q-factor that allows for operating at low energy levels. This emerging field gains importance when considering most of the biochemical reactions that occur in aqueous environments. Optofluidic laser systems are flexible to change their optical properties by just replacing the liquid media; and with this twist, lasers have new application areas including diagnosis of genetic disorders at the cellular level and in vivo biosensing.

What is more exciting about the optofluidic lasers is that they can be biodegradable and easily tunable in microenvironments. Researchers in University of Michigan recently showed that one of the most abundant pigments on earth, chlorophylls, can maintain both biodegradability and tunability in optical systems owing to their fluorescence capabilities. Chlorophylls have a high Q-factor, dual-absorption bands in the visible spectrum, and a large shift between absorption and emission bands, suggesting that chlorophylls can be used as donors in fluorescence resonance energy transfer (FRET) laser (Figure 1). In this study, chlorophyll a was isolated from spinach leaf and used as the gain medium and the donor to develop a novel optofluidic laser. Two lasing bands of chlorophyll a was investigated by both theoretical and experimental means. Concentration-dependent studies enabled more insight for the mechanism determining when, where, and why the laser emission band appears. This new technique seems to gain increasing attention for applications in in vivo and in vitro biosensing, solar lighting and energy harvesting.

This article, published on 12th May 2016, is included in the Lab on a Chip Recent HOT Articles themed collection.

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

Optofluidic chlorophyll lasers
Yu-Cheng Chen, Qiushu Chena, Xudong Fan
Lab Chip, 2016, 16, 2228-2235
DOI: 10.1039/C6LC00512H

About the Webwriter

Burcu Gumuscu is a PhD researcher in BIOS Lab on a Chip Group at University of Twente in The Netherlands. Her research interests include development of microfluidic devices for second generation sequencing, organ-on-chip development, and desalination of water on the micron-scale.

*Access is free until 23/09/2016 through a registered RSC account.

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What is the best way to study brain?

Before the 1700’s, when dissection techniques were not yet available, the cause of mood changes were thought to be the replacement of liquids and vapors in the body. The biology of the brain has been better understood since the discovery of research and test tools. However, occupying only about 1/50 of the body mass, the brain is perhaps the most complicated organ to study. National Institute of Neurological Disorders and Stroke’s list of over 400 neurological disorders can be seen as a sound proof of this exciting- and frustrating- fact.

Figure 1. The effects of biomechanical forces on the brain

Biomechanical forces on neurons play a fundamental role in neuronal physiology, which, in turn, affect brain development and disorders. During the growth of neurons, the tension created by the biomechanical forces are suggested to influence the cells’ motor activities, gene expression, neurotransmitter release, together with neurite growth and network connections (Figure 1). Research on the biomechanical forces can definitely help us to understand how the brain works, but many questions related to these forces remain unanswered. Quantitative measurements of the cell activity seem to be the only possible path to find satisfying answers to those questions.

A comprehensive list of experimental techniques involving both conventional and alternative micro&nanotechnology approaches have been recently brought to the attention of scientific community by Di Carlo and his coauthors. In their recent critical review, both advantages and disadvantages of conventional toolsnamely motor-driven pressure, patch membrane pressure, osmotic pressure, fluid shear stresses, and deformation of flexible elastomers—, microtechnology toolsincluding atomic force microscopy, micropatterning, and some other potential techniques—, and nanotechnology toolssuch as ferromagnetic and piezoelectric nanoparticles— are discussed.

The literature reports provided in the paper suggest that micro and nanotechnology tools offer better spatiotemporal resolution and throughput when compared to conventional techniques. The cellular functions and the possible technologies for the characterization of those functions are further described (Figure 2). For instance, behind-the-scene biological mechanisms for recovery in traumatic brain injuries can be determined by applying the biomechanical forces at the right place and right time to ultimately mitigate the injuries.

Figure 2. The influence of biomechanical forces on the neuron functions and available technologies for their investigation.

This article, published on 26 April 2016, is included in the Lab on a Chip Recent HOT Articles themed collection.

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

Micro- and nano-technologies to probe the mechano-biology of the brain
Andy Tay, Felix E. Schweizer, and Dino Di Carlo
Lab Chip, 2016,16, 1962-1977
DOI: 10.1039/C6LC00349D, Critical Review

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About the webwriter

Burcu Gumuscu is a PhD researcher in BIOS Lab on a Chip Group at University of Twente in The Netherlands. Her research interests include development of microfluidic devices for second generation sequencing, organ-on-chip development, and desalination of water on the micron-scale.

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*Access is free until 15/08/2016 through a registered RSC account.

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Implanted tumour within a transparent chamber allows analysis of tumours in vivo

Lance Munn and co-workers at Massachusetts General Hospital have developed tissue isolation chambers that can be implanted into the brain or skin of mice beneath a transparent window, to allow host-tumour interactions to be observed over a timescale of weeks to months. A small tumour fragment from a donor mouse was placed within the shallow ‘tumour isolation chamber’ and implanted into another mouse, forcing any vasculature and connective tissue (stroma) to occur in an essentially 2D space. Fluorescent reporters were then used to visualise specific components of the tissue.

Different implantable tissue isolation chambers that were developed. a) 'raft' model; b) 'hole' model; c) 'pillar' model; d) transparent window models in the dorsal skin or brain

By using a shallow chamber, this new method overcomes some of the limitations of other systems used for studying tumour microenvironments and stromal remodelling processes. Other in vivo mouse models use fluorescent reporter and even transparent windows, however the penetration depth of optical microscopy is only a few hundred micrometers, preventing observations below this depth in the tissue. By using tissue chambers of around 150 µm, this issue is circumvented. Another problem can be in visualising structures that extend in the direction, as they may overlap and be hidden; this is overcome in this work by allowing freedom of movement in the x-y plane, while restricting movement or growth in the z direction.

In the studies carried out by the authors, tumour angiogenesis was clearly observed and was found to show the same properties usually observed in tumours. It was also found that migrating blood vessel sprouts were closely associated with bundles of collagen fibres, providing the first evidence for matrix-guided sprouting in tumour angiogenesis. The tissue isolation chambers also allowed analysis of processes that are difficult to study through other methods, due to either the short distances involved, low frequency of occurrence, or rapid dynamics.

Image sequence showing the expansion of vessel sprouts and vascular loops in the tumour isolation chamber. D1=day 1, etc. Pillar structure is indicated by an asterix.

One potential application of this technology highlighted by the authors, is to provide vascularised tissues for transplantation, allowing good blood supply to the transplanted tissue immediately after implantation. In the experiments reported in this paper, stable and mature vasculature was formed that remained functional for more than 2 months after the tissue chambers were implanted. Although these initial findings are very positive, further studies would need to be carried out on a wide range of tissue types.

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

Implantable tissue isolation chambers for analyzing tumor dynamics in vivo
Gabriel Gruionu, Despina Bazou, Nir Maimon, Mara Onita-Lenco, Lucian G. Gruionu, Peigen Huang and Lance L. Munn
Lab Chip
, 2016,16, 1840-1851
DOI:
10.1039/C6LC00237D

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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 30/06/2016 through a registered RSC account – click here to register

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One big step towards building “body-on-a-chip”

It takes about 14 years and 2 billion dollars to bring a successful drug from laboratory to clinic. A large portion of this time period includes in vitro culture tests, animal tests, and clinical trials. The overall success rate of a new drug molecule making it through this entire process is only around 10%. To improve this situation, there has been a tremendous amount of work in recent years on developing in vitro organ-on-chip models. Many organ-on-chip platforms (including heart, lung, kidney, liver, and intestine) have shown to mimic organ functions on the microscale, offering the possibility to eliminate animal testing, shorten long development times, and reduce costs. More importantly, such platforms can offer personalized medicine, enabling drug molecules to be tested directly on individual patient cells without adverse side-effects or harm.

Figure 1. The concept of elastomeric endothelialized blood vessels for interconnecting multiple organs on chip systems (liver, heart, and lung modules as illustrated).

Although existing organ-on-chip models have been shown to function well individually, integrating all models into a single fluidic circuitry (or “body-on-a-chip”) remains a necessary goal to recapitulate multi-physiological functions (Figure 1). Passive tube connections and chip-based vessels have thus far been utilized for this purpose. However, bulky dead volumes created in connections, and unbalanced scaling of the volumes between organ models and chip-based vessels, seem counterintuitive to the miniaturized nature of microscale platforms. These methods may also result in miscommunication between the organ models due to the dilution of the signal molecules secreted by the cells.

This fundamental problem has recently been addressed in a practical way by Khademhosseini and co-workers, who are the first to develop polydimethylsiloxane (PDMS) hollow tubes in a range of different sizes and wall thicknesses which mimic the physio-anatomical properties of blood vessels. The fabrication of the PDMS tubes was enabled by two different strategies, including both hard and soft templating (Figure 2a). After fabrication, the tube’s interior surface was coated with human umbilical vein endothelial cells (HUVEC) to introduce biological functions (Figure 2b). The biofunctionality of the elastomeric blood vessels was demonstrated by the expression of an endothelial biomarker and dose-dependent responses in the secretion of von Willebrand factor. The endothelialized PDMS tubes were also utilized for assessing a panel of drugs, including the anti-cancer drug doxorubicin, immunosuppressive drug rapamycin, and vasodilator medication minoxidil, as well as amiodarone, acetaminophen, and histamine (Figure 2c). Functional elastomeric blood vessels can be fabricated up to 20 cm in length, which is sufficient for interconnecting the organ-on-chip models. Moreover, tailorable wall thicknesses enable the opportunity to study various disease models, such as the effect of diabetes or hyperlipidemia on blood vessels. The elastomeric blood vessels are expected to replace the current technologies in assembling human organ-on-chip models.

Figure 2. (a) The elastomeric PDMS blood vessels fabricated using hard and soft templating. (b) A blood vessel template with 0.28 mm diameter is used to culture HUVEC. F-actin (green) and DAPI (blue) staining are performed to visualize the cytoskeletons and the nuclei of the cells. Scale bars are 200 μm. (c) The cell growth in the templates are further shown by live (green) and dead (red) staining under application of several drugs, including Doxorubicin (anti-cancer drug) and Minoxidil (a vasodilator usually used for treatment of severe hypertension). Scale bars are 50 μm.

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

Elastomeric free-form blood vessels for interconnecting organs on chip systems
Weijia Zhang, Yu Shrike Zhang, Syeda Mahwish Bakht, Julio Aleman, Kan Yue, Su-Ryon Shin, Marco Sica, João Ribas, Margaux Duchamp, Jie Ju, Ramin Banan Sadeghian, Duckjin Kim, Mehmet Remzi Dokmeci, Anthony Atala, and Ali Khademhosseini
Lab Chip
, 2016, 16, 1579-1586
DOI: 10.1039/C6LC00001K, Advance Article

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About the webwriter

Burcu Gumuscu is a PhD researcher in BIOS Lab on a Chip Group at University of Twente in The Netherlands. Her research interests include development of microfluidic devices for second generation sequencing, organ-on-chip development, and desalination of water on the micron-scale.

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*Access is free until 17/06/2016 through a registered RSC account.

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