Archive for the ‘Cover articles’ Category

Keeping a remote eye on the microworld

Creating a lab-on-chip device with multiple sensing capabilities has been a long-desired goal in the biotechnology field. A sensor-rich chip would pack the power of a full-scale laboratory as initially envisioned in the lab on a chip concept, yet it remained challenging for decades. Many researchers suggest that real-time monitoring of the culture conditions can provide higher-quality drug screening testing. Although many platforms have been proposed up till now, none of them has yet taken off. A recent work from Andreas Weltin’s laboratory at IMTEK published in the Lab on a Chip, however, sounds very promising.

Embedding the cells in synthetic or natural 3D matrices makes it possible to mimic an in vivo cellular environment, but also frequently takes away control over the culturing conditions. The present microfluidic platform achieves the spheroid growth of tumor cells using Matrigel for several days. However, without continuous monitoring, large amounts of independent cultures would be necessary, as each must be sacrificed to conduct separate assays at separate time points, raising the degree of uncertainty in statistical analysis. The authors addressed this problem by integrating several sensors which can perform continuous readout of different molecules.

Creating hypoxia (low oxygen levels) or hyperoxia (high oxygen levels) conditions in cell culture is often needed to mimic disease conditions for fundamental studies. On the other hand, monitoring the local oxygen levels in a culture is not straightforward. In the present study, the authors fabricated the reference electrodes by electroplating silver/silver chloride. The oxygen sensors were modified using a platinum-coated surface located at multiple spots in close vicinity of the culture chamber, allowing for a comparison of the initial and waste streams (Figure 1).

Cell metabolism underpins cell activity, as well as its viability. Some of the key parameters to monitor cell metabolism include glucose and lactate concentrations in the culture media. While high uptake of glucose is indicative of faster cell respiration and replication, high production of lactate is indicative of an increased anaerobic respiration rate. The authors embedded enzymatic sensors in hydrogel to measure glucose and lactate levels. Regions with lactate oxidase and glucose oxidase enzymes are strategically located in close vicinity to the culture chamber. Such locations were ideal because the cell metabolites released into the media are not yet diffused to a lower concentration at this spot, while it is far enough from the chamber so the by-products of the enzymatic reaction cannot interfere with the cell culture (Figure 1).

As a proof-of-concept, Weltin’s team applied this multifunctional sensing platform to the growth of patient-derived triple-negative breast cancer stem cells, which are highly metastatic and less responsive to treatment. The developed platform unveiled the difference in temporal and concentration-dependent drug response of the cells in spheroids. The authors state that this work underlines the importance of in situ, real-time metabolite monitoring in 3D cell cultures as a future standard in cancer research-related studies.

chip with multiple sensors

Figure 1. The layout of the microfluidic chip. The authors created a compartmentalized matrix-embedded cell culture with medium perfusion and rigorous control of the liquid and gas composition in one platform but also incorporated continuous sensors that are capable to deliver real-time readouts of the oxygen concentrations and cell metabolism by-products.

 

About the Web writers

Burcu Gumuscu is an assistant professor at Eindhoven University of Technology in the Netherlands, and the chair of the Biosensors and Devices Laboratory. She strives for the development, fabrication, and application of smart biomaterials to realize high-precision processing in high-throughput microfluidic settings. She specifically focuses on the design and development of lab-on-a-chip devices containing hydrogels for diversified life sciences applications.

OksanaSavchak

 

Oksana Savchak is a Ph.D. student in Biosensors and Devices Laboratory at the Eindhoven University of Technology in the Netherlands. She focuses on the development of microfluidic screening platforms to investigate cell-material interactions.

 

Original publication

Dornhof, J., Kieninger, J., Muralidharan, H., Maurer, J., Urban, G. A., Weltin, A. (2022): Microfluidic organ-on-chip system for multi-analyte monitoring of metabolites in 3D cell cultures. In: Lab on a Chip, 22 (2). DOI: 10.1039/d1lc00689d

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Why should we use optofluidics for monitoring marine environment?

Phosphorus is found in natural waters and exerts a major influence on the composition and structure of aquatic ecosystems. It is a crucial nutrient for planktons and algae, which feed fish and other marine organisms. However, human activities may result in excess amount of phosphorus, which, in turn, causes harmful algae to bloom in natural waters. The bloom creates a hostile environment to other forms of marine life by consuming the available oxygen in the sea, and producing toxins. Sea organisms such as fish swim away from the blooms, but the ones that cannot swim, such as shellfish, unfortunately die. We do care about this occurrence as it negatively affects natural life and the economy. There is only one way to interpret the effect of continuously changing phosphorus levels on the strength of the biological pump: real-time monitoring of phosphate levels in the marine environment!

Figure 1. The design of the Fabry-Pérot microcavity, consisting of two parallel mirrors (reflectors) fabricated by coating the surface of the optical fibers with a gold layer. The light is reflected by the mirrors multiple times to enhance the signal. Adapted from Zhu et al., 2017.

Conventional vs. optofluidic monitoring instruments

Conventional phosphate monitoring instruments are mostly used for on-site sampling, then the fresh sample is transported to a laboratory for determining the phosphate level. Laboratories complete one round of analysis in 20 min, often using spectrophotometrical measurement tools. Given the conditions, real-time phosphate monitoring easily becomes laborious, time consuming, and costly. To address this challenge, researchers in Chinese Academy of Sciences, Wuhan University, and The First Institute of Oceanography in China collaborated to develop a portable optofluidic phosphate monitoring tool. However, prototyping an optofluidic marine phosphate detection tool is not straightforward because an absorption cell—a component core to the measurement unit—is simply too big to fit in a microchip. Instead of using a bulky absorption cell, researchers considered integrating a Fabry-Pérot cavity in the microsystem. The Fabry-Pérot cavity consists of two parallel optical fibers with a spacing in between. The cross-sectional surface of each optical fiber is coated with a thin layer of gold to create reflector surfaces (Figure 1) in order to enhance the absorption of phosphate. Shortening the spacing between the reflectors decreases the analysis time from minutes to seconds.

 

How it works?

In the microchip, filtered water sample and a chromogenic reagent are injected into a curved microchannel. After the chromogenic reaction, the water-soluble components are transported into the optical section (Figure 2). The probe light is sent into the Fabry-Pérot cavity via one of the fibers, bounces between the reflectors multiple times to increase the optical feedback and then analyzed by the detector. The obtained absorbance value, therefore, increases linearly with increasing phosphate concentration. In this microsystem, phosphate detection range is 0.1-100 µmol per liter (400 times greater than the range of a conventional instrument) and detection time is 4 seconds (300 times shorter than detection time of a conventional instrument). The authors of the paper think that this technology can be applied to detect other nutrient levels as well as pH changes in marine environment.

 

optofluidic phosphate monitoring

Figure 2. A schematic of the optofluidic microchip consisting of two parts: the microfluidics circuit forming the microreactor in the microchannel, and the optical part to provide optical feedback for enhanced absorption analysis. Adapted from Zhu et al., 2017.

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

 

Optofluidic marine phosphate detection with enhanced absorption using a Fabry–Pérot resonator

M. Zhu, Y. Shi, X. Q. Zhu, Y. Yang, F. H. Jiang, C. J. Sun, W. H. Zhaoc, and X. T. Hanc

Lab Chip, 2017, Lab on a Chip Recent Hot Articles

DOI: 10.1039/C7LC01016H

 

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.

*until 16th February 2018

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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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Saving Stripes: using gratings to prevent destructive air-water interfaces

Researchers at National Taiwan University design grating structures to prevent air-water interfaces from destroying lipid bilayers, enabling robust bioassays of synthetic membranes.

Supported lipid bilayers (SLBs) are useful as platforms to simulate cell membranes for evaluating transport of toxins and viral particles1 and screening new pharmaceutical reagents. Yet a significant challenge is maintaining the integrity of SLBs throughout an experiment. Air-water interfaces, commonly formed during reagent changes and rinses, peel apart SLBs and delaminate them from the substrate. Strategies to preserve SLB integrity involve coating SLBs with polymers to increase their rigidity or adding proteins and sugars to form protective layers with a high bending modulus above the membrane. These methods modify the chemical structure and environment of SLBs, preventing analysis of membrane properties and specific assays of membrane-tethered species. Thus, Chung-Ta Han and Ling Chao developed a substrate with patterned gratings to prevent air-water interfaces from directly contacting SLBs when an air bubble is introduced into a microchannel with SLBs.Han2015_Figure2

The grating structures, fabricated by standard photolithography, are perpendicular to fluid flow in the microchannel and act as obstacles to air-water interfaces contacting SLBs directly by a ‘tenting’ mechanism (see figure at right). Holding the obstacle height constant at 2 μm, Han and Chao evaluated obstacle spacing at different flow rates influenced SLB stability after treatment with an air bubble. 40 μm spacing was found to efficiently preserve SLBs from air-water interfaces at a practical range of flow rates: 60 – 6000 mm/min. The authors also confirmed the integrity of the membranes by comparable diffusivity measurements within the SLBs before and after air-bubble treatment. Finally, the authors demonstrated that air bubbles did not affect receptor-ligand interactions between species embedded in the SLBs and surrounding buffer when SLBs were protected using the microfabricated obstacles.

This platform uses integrated barriers to protect SLBs from air-water interfaces, creating SLBs with native properties to study biomolecule behavior within membranes and perform high throughput analytical assays utilizing synthetic membranes.

Download the full article now – free* access for a limited time only!

Using a patterned grating structure to create lipid bilayer platforms insensitive to air bubbles
Chung-Ta Han and Ling Chao. Lab Chip, 2015, 15, 86 – 93.
DOI: 10.1039/c4lc00928b
[1] I. Kusters, A. M. Van Oijen and A. J. Driessen, ACS Nano, 2014, 8, 3380-3392.

*Access is free until 06.02.15 through a registered RSC Publishing account.

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Lectureship presented to Sangeeta Bhatia

Congratulations to Dr. Sangeeta N. Bhatia, winner of  the 2014 Corning Inc./Lab on a Chip Pioneers of Miniaturisation Lectureship.


The picture shows Lab on a Chip Executive Editor, Harpal Minhas (Left) and Director of Polymer processing in Organic & Biochemical Technologies, Science & Technology at Corning Incorporated, Ed Fewkes (right) presenting Sangeeta (middle) with her award earlier this week at the µTAS 2014 Conference.

The 9th ‘Pioneers of Ministurisation‘ Lectureship, is for extraordinary or outstanding contributions to the understanding or development of miniaturised systems and was presented to Dr Bhatia at the µTAS 2014 Conference in San Antonio, Texas in October 2014. Dr Bhatia received a certificate, $5000 and gave a short lecture at the conference. Further information, including past winners, can be viewed on our homepage.

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LOC Issue 11 online! 3D etching, digital microfluidics, lens-free microscopy

Issue 11’s significant front cover article from Ikuro Suzuki et al. at Tokyo University of Technology, Japan, describes the development of a new 3D etching method. An infrared laser allows tight control over the area of cell adhesion, selecting cell number and cell type, as a small area of the collagen gel substrate can be targeted. The researchers can guide neural network formation using this tool. 3D networks are created upon which neurons survived longer than on 2D substrates.

Control of neural network patterning using collagen gel photothermal etching
Aoi Odawara, Masao Gotoh and Ikuro Suzuki 
DOI: 10.1039/C3LC00036B

Work from Jeoren Lammertyn et al. is featured on the inside front cover. The team from University of Leuven, Belgium, use digital microfluidics to facilitate single-molecule detection for the first time. They are able to print and seal thousands of femtolitre droplets in microwells in each step. Single paramagnetic beads can be loaded into the microwells with high capacity.

Digital microfluidics-enabled single-molecule detection by printing and sealing single magnetic beads in femtoliter droplets
Daan Witters, Karel Knez, Frederik Ceyssens, Robert Puers and Jeroen Lammertyn  
DOI: 10.1039/C3LC50119A

A Frontier article from Aydogan Ozcan et al. at University of California, Los Angeles, USA, discusses progress in computational lens-free microscopy on-chip and how such technology is taking over conventional bulky optical microscopes. This article, which is also featured on the back cover, includes a discussion of the applications this new technology opens up.

Toward giga-pixel nanoscopy on a chip: a computational wide-field look at the nano-scale without the use of lenses
Euan McLeod, Wei Luo, Onur Mudanyali, Alon Greenbaum and Aydogan Ozcan
DOI: 10.1039/ c3lc50222h

For more critical reviews, HOT primary research as recommended by referees and Technical Innovations, take a look at the full issue now

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HOT articles and technical innovations in point-of-care flow cytometry

A team from Caltech and MIT, USA, and LeukoDx, Israel, have combined a microflow cytometer and fluorescent dye to produce a portable suitcase-sized point-of-care test for leukocyte count – one of the most common clinical tests. The test can identify four different types of leukocyte using only a small blood sample.

This article was featured on the bright cover of Issue 7!

Four-part leukocyte differential count based on sheathless microflow cytometer and fluorescent dye assay
Wendian Shi, Luke Guo, Harvey Kasdan and Yu-Chong Tai 
DOI: 10.1039/C3LC41059E


 

A technical innovation from Oliver Hayden and Michael Helou et al. in Germany featured on the outside front cover of Issue 6 also concentrates on flow cytometry for point-of-care testing. This vastly different technique uses magnetophoresis instead of fluorescence to detect specific cancer cells in whole blood. Cell diameters are measured from time of flight information. The device integrates sample preparation for ease of point-of-care applications. The can perform cell enrichment, cell focusing and background elimination in situ.

Time-of-flight magnetic flow cytometry in whole blood with integrated sample preparation
Michael Helou, Mathias Reisbeck, Sandro F. Tedde, Lukas Richter, Ludwig Bär, Jacobus J. Bosch, Roland H. Stauber, Eckhard Quandt and Oliver Hayden  
DOI: 10.1039/C3LC41310A

Remember all of our HOT articles are made free to access for 4 weeks*!

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

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Issue 10 online today! Artificial skin, robust SPR sensing platform and plenty of Technical Innovations

Research led by Jan van Hest and Floris Delft at the Institute for Molecules and Materials, The Netherlands, is highlighted by the front cover artwork. Their research finds a robust way to control the immobilization of azide-containing ligands on a surface for surface plasmon resonance sensing (SPR) using strain-promoted cycloaddition on a cyclooctyne-modified surface. Don’t forget our cover articles are free to access for 6 weeks*!

Site-specific peptide and protein immobilization on surface plasmon resonance chips via strain-promoted cycloaddition Angelique
E. M. Wammes, Marcel J. E. Fischer, Nico J. de Mol, Mark B. van Eldijk, Floris P. J. T. Rutjes, Jan C. M. van Hest and Floris L. van Delft  
DOI: 10.1039/C3LC41338A


 

On the distinctive outside back cover, fascinating collaborative work between the Ohio Center for Microfluidic Innovation at University of Cincinnati and the U.S. Air Force Research Laboratory on a device termed artificial microfluidic skin, which mimics human perspiration with a view to replacing human and animal testing of wearable materials.  

Artificial microfluidic skin for in vitro perspiration simulation and testing
Linlin Hou, Joshua Hagen, Xiao Wang, Ian Papautsky, Rajesh Naik, Nancy Kelley-Loughnane and Jason Heikenfeld  
DOI: 10.1039/C3LC41231H


 

Of course Issue 10 also includes Research Highlights from Ali Khademhosseini. In this issue, he focuses on lab-on-DVD devices for HIV diagnosis, atherosclerosis and muscle repair.

Research highlights
João Ribas, Mark W. Tibbitt, Mehmet R. Dokmeci and Ali Khademhosseini 
DOI: 10.1039/C3LC90032K


 

Issue 10 contains plenty of significant primary research, including three Technical Innovation articles:

Measuring material relaxation and creep recovery in a microfluidic device
Alison E. Koser, Lichao Pan, Nathan C. Keim and Paulo E. Arratia
DOI: 10.1039/C3LC41379A

Optically clear alginate hydrogels for spatially controlled cell entrapment and culture at microfluidic electrode surfaces
Jordan F. Betz, Yi Cheng, Chen-Yu Tsao, Amin Zargar, Hsuan-Chen Wu, Xiaolong Luo, Gregory F. Payne, William E. Bentley and Gary W. Rubloff
DOI: 10.1039/C3LC50079A

Multiplexed ionic current sensing with glass nanopores
Nicholas A. W. Bell, Vivek V. Thacker, Silvia Hernández-Ainsa, Maria E. Fuentes-Perez, Fernando Moreno-Herrero, Tim Liedl and Ulrich F. Keyser
DOI: 10.1039/C3LC50069A

Have a quick browse of the contents pages of Issue 10 here

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

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HOT article: Low cost, miniaturised, thermoplastic SPR biosensor

SPR biosensorAs featured on the bright inside front cover of Issue 5, this HOT article from Teodor Veres and colleagues at the National Research Council and McGill University, Canada, steps towards low cost point-of-care sensors for disease diagnosis.

The team present their all-polymeric nanoplasmonic microfluidic (NMF) transmission surface plasmon resonance (SPR) biosensor. SPR, involving light stimulated electron oscillation, is advantageous for sensing as it means label-free, real-time detection with high throughput and automation. The device is miniaturised with a view to small, point-of-care applications. The approach involves nanostructures called nanogratings for transmission SPR, which gives a more stable response. The signal can be turned by altering their characteristics and they are easily fabricated en mass.

Thermoplastic materials present an advantage over traditional PDMS for such miniaturised SPR devices as they are more mechanically robust, inert, transparent and crucially viable for large scale production and commercial applications.  The novel aspect of this work is that the nanostructured surface and the microchannels are incorporated into one substrate quickly and at low cost. Thermoplastic valves are used in large numbers for the first time for a multiplex detection scheme.

They demonstrate its application in sensing glycoprotein sCD44 at picomolar to nanomolar concentrations. Further work by the group is focused on integrating this device with a CCD spectrometer.

See the design and performance results in the full paper, now available free for 4 weeks*:

All-thermoplastic nanoplasmonic microfluidic device for transmission SPR biosensing
Lidija Malic, Keith Morton, Liviu Clime and Teodor Veres
DOI: 10.1039/C2LC41123G

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LOC Issue 9 online! Micronanofabrication, neurotransmitters, SAW-controlled droplets and pharmaceutical screening

Abraham LeeThe packed Issue 9 begins with an editorial celebrating over three decades since the birth of microfluidics by Lab on a Chip Associate Editor Abraham Lee.

Submit your work to his editorial office today at http://mc.manuscriptcentral.com/lc!

The third decade of microfluidics
Abraham Lee
DOI: 10.1039/C3LC90031B


 

An urgent communication from Lothar Schmid and Thomas Franke at University of Augsburg, Germany, and Harvard University, USA, is featured on the outside front cover, in which a surface acoustic wave is applied to control droplet size in real time:

SAW-controlled drop size for flow focusing
Lothar Schmid and Thomas Franke
DOI: 10.1039/C3LC41233D

The inside front cover illustrates the work of researchers in New Zealand and Beijing led by Wenhui Wang who investigate locomotion metrics and muscular forces of C. elegans in one microfluidic assay:

On-chip analysis of C. elegans muscular forces and locomotion patterns in microstructured environments
Shazlina Johari, Volker Nock, Maan M. Alkaisi and Wenhui Wang
DOI: 10.1039/C3LC41403E


Issue 9 includes one Tutorial Review on using microfluidics to study neurotransmitters from Callie Croushore and Jonathan Sweedler at University of Illinois at Urbana-Champaign, USA, and one Critical Review discussing micronanofabrication techniques:

Microfluidic systems for studying neurotransmitters and neurotransmission
Callie A. Croushore and Jonathan V. Sweedler
DOI: 10.1039/C3LC41334A

Fabrication and multifunction integration of microfluidic chips by femtosecond laser direct writing
Bin-Bin Xu, Yong-Lai Zhang, Hong Xia, Wen-Fei Dong, Hong Ding and Hong-Bo Sun
DOI: 10.1039/C3LC50160D

The high quality research published in Issue 9 includes a HOT article from Paul Kenis et al. again at the University of Illinois at Urbana-Champaign, USA, which describes a new microfluidic platform for the screening of salt forms of pharmaceuticals:

Microfluidic Platform for Evaporation-based Salt Screening of Pharmaceutical Parent compounds
Sachit Goyal, Michael R. Thorson, Cassandra L. Schneider, Geoff G. Z. Zhang, Yuchuan Gong and Paul J. A. Kenis
DOI: 10.1039/C3LC41271G

View all of the articles in Issue 9 here

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