Lab on a Chip Blog

The function of tissues degrade during the course of human life, whether the cause is genetics, accidents, or wear and tear. Frequently experienced medical conditions associated with aging include blocked arteries, cataracts, and arthritis. The former two can be thoroughly treated via surgeries, but arthritis remains a bane to millions of sufferers because its treatment is rather palliative than intensive.

Let’s take the example of rheumatoid arthritis. It occurs when macrophage cells (a main component of the immune system) attack to the membrane (synovium) that surrounds the joints as a result of an auto-immune response. The damaged synovium thickens significantly, its anatomy undergoes striking changes such as metabolic activation of synoviocytes and continuous mass of cells invading into the cartilage and bone. If unchecked this inflammation can destroy the cartilage and the bone within the joint. What does this mean for the patients? A relatively short answer is painful knees, reduced physical activities, continuous uptake of anti-inflammatory medication, and painkillers. A cure does not yet loom on the horizon, but new tools to model rheumatoid arthritis could definitely make it easier to predict the onset of the disorder.

Peter Ertl and his colleagues at Vienna University of Technology, Austria, decided to tackle this problem in the article they recently published in Lab on a Chip. They researched the mechanisms governing the destructive inflammatory reaction in rheumatoid arthritis by designing a first-ever 3D synovium-on-chip tool, which can monitor the onset and progression of the tissue responses. The researchers were focused on monitoring the behavior of the inflated fibroblast-like synoviocytes, which makes the synovium membrane thicker. They used tumor necrosis factor-alpha (TNF-α) to trigger synoviocytes to demonstrate inflammation response. The chips contained circular microchambers, where surface coatings are applied and Matrigel is filled for obtaining 3D organoids. Different hydrogel types were also examined to observe cell response. For the monitoring, the researchers used collimated laser beams, and the scattered light was collected using embedded organic photodiodes. This powerful optical measurement setup allowed for adjusting the detection range (50 nm to 10 µm) and sensitivity to any tissue construct (Figure 1). The researchers implemented a PDMS waveguide structure to the optical measurement setup to turn the light scattering measurements into reproducible ones. The measurement setup also enabled continuous monitoring of hydrogel polymerization, which was also controlled in this work since the polymerization time influences hydrogel stiffness, which in turn affects the fate of cell behavior. A typical measurement took four days, where the researchers obtained cultures accurately mimicking in-vivo rheumatoid arthritis conditions. A diseased phenotype becomes distinguishable within 2-3 days in the organ-on-chip platform, as this takes at least 14 days in conventional cell culture platforms. The developed tool can very well serve as a new modeling system for inflammatory arthritis and joint-related disease models.

Figure 1. Overview of the synovium-on-a-chip system with integrated time-resolved light scatter biosensing.

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Monitoring tissue-level remodelling during inflammatory arthritis using a three-dimensional synovium-on-a-chip with non-invasive light scattering biosensing

Mario Rothbauer, Gregor Höll, Christoph Eilenberger, Sebastian R. A. Kratz, Bilal Farooq, Patrick Schuller, Isabel Olmos Calvo, Ruth A. Byrne, Brigitte Meyer, Birgit Niederreiter, Seta Küpcü, Florian Sevelda, Johannes Holinka, Oliver Hayden, Sandro F. Tedde, Hans P. Kiener and Peter Ertl, Lab Chip, 2020, Lab on a Chip Hot Articles

DOI: 10.1039/c9lc01097a

About the Webwriter

Burcu Gumuscu is an assistant professor in BioInterface Science Group at Eindhoven University of Technology in the Netherlands. 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. She is also interested in combining data-mining and machine learning techniques with hypothesis-driven experimental research for future research.

Our skin perspires every day by about 2.5 million sweat glands under the dermis layer. Not all the sweat glands have the same function. While some glands release sweat through the opening of hair follicles−aka apocrine glands−, some others open directly onto the skin surface−aka eccrine glands−. The most prevalent type in the body is the eccrine glands, which produce interesting signaling subtleties for monitoring health. Actually, the sweat produced at different times contains the time-stamps of noteworthy information such as electrolytes, metabolites, micronutrients, hormones exogenous agents, each of which can change in concentration in the content of sweat with diet, stress level, hydration status, and physiologic or metabolic state. Monitoring these cues using appropriate sensors makes possible to track an individual’s health in real-time. Sweat analysis potentially complements or even obviates the need for approaches relying on puncturing the skin with needles.

We encounter two major types of skin-interfaced measurement units in the literature: (1) equipped with electronics to power measurement units or run electrochemical measurements (2) colorimetric detection relying on no electronic sensors. Each type has different application areas. The colorimetric detection is particularly interesting as it relies on uniquely designed rapid chemical reactions between the sweat and the unit, in many cases with improved repeatability and accuracy. As a recent example of this kind, a research team from Northwestern University and the University of Illinois at Urbana-Champaign have introduced a skin sensor to detect signaling subtleties emanating from the skin. The promise of this work lies in the ability to control the reaction kinetics and the mixing of different reagents and samples in a user-operated device. This achievement was made possible by introducing a multi-layered microfluidic device platform containing stop valves and a super absorbent polymer to initiate colorimetric reactions for microliter volumes of ammonia and ethanol in microliter volumes of sweat.

The patch absorbs sweat via super absorbent polymer layers located subjacent to individual wells (Figure 1). The super absorbent polymer layer expands upon soaking sweat, activating a microfluidic mechanical pump that releases pre-loaded reaction buffers into the wells. The colorimetric reaction subsequently takes place (Figure 1). This pad was equipped for running ammonia and ethanol (alcohol) assays. But why two metabolites only? The patch is dedicated to monitoring alcohol testing in daily living. As mentioned in the paper, ammonia levels could serve as an index for hepatic encephalopathy diagnosis in subjects who are experiencing alcohol abuse. Hepatic encephalopathy refers to liver failure mostly caused by alcohol uptake. The researchers also tested the patch on volunteers resting in a warm bath after consuming alcoholic beverages to highlight the operational advantages of such patches. The authors note that this work has direct implications for sweat biomarker research, health monitoring in daily life, and simultaneous drug/alcohol testing.

Figure 1. The skin-interfaced measurement patch, its measuring units, and working mechanism.

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Soft, skin-interfaced microfluidic systems with integrated enzymatic assays for measuring the concentration of ammonia and ethanol in sweat

Sung Bong Kim, Jahyun Koo, Jangryeol Yoon, Aurélie Hourlier-Fargette, Boram Lee,f Shulin Chen, Seongbin Jo, Jungil Choi, Yong Suk Oh, Geumbee Lee, Sang Min Won, Alexander J. Aranyosi, Stephen P. Lee, Jeffrey B. Model, Paul V. Braun, Roozbeh Ghaffari, Chulwhan Park and John A. Rogers, Lab Chip, 2020, Lab on a Chip Hot Articles

DOI: 10.1039/c9lc01045a

About the Webwriter

Burcu Gumuscu is a researcher in Mesoscale Chemical Systems Group at the University of Twente in the Netherlands. Her research interests include the 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.

A picoliter of a droplet is approximately 1 µm. It is so small that a raindrop can contain thousands of picoliters. Despite the small quantity, precise control of picoliter size liquids spawns a growing number of applications including in point-of-care tools and drug synthesis. Such a task is not easy to achieve for conventional liquid-manipulation methods due to precision, evaporation and the ease of post-processing problems.

When it comes to small volume liquid handling, no other platform would be better than microfluidic devices. As such, a recent Lab Chip paper from Prof. Bai Yang’s Lab at Jilin University in China demonstrates the fabrication of a microfluidic platform to handle sub-picoliter size droplets. The authors use glass as the core material of the microchips because glass is mechanically strong and it enables higher precision in droplet manipulation (Figure 1). In the paper, pressure-controlled syringes are used to dispense down to 0,5 picoliters in a series of trapezoidal-shaped microchambers, each composed of 10 subunits. The boundaries of the subunits act as pressure barriers, preventing the liquid from flowing through the entire microchamber and allowing for fine-tuning of the volume to be handled. The authors also showed that the working range, stability, and precision of the device could be increased by adjusting the boundary properties and microchamber dimensions (e.g., height). However, the magnitude of the minimum volume will still be bound to two main factors. (1) The resolution of the fabrication technology determines the microchannel and boundary dimensions. (2) Laplace pressure difference between the channel and the boundaries determines the accuracy of the device. The smaller channels yield decreased accuracy due to higher pressure differences between the boundary-microchannel interfaces. Relying on these design criteria, the authors fabricated up to three interconnected picoliter-volume injection units. Combined units work together to synthesize gold nanoparticles and nanorods with a wide size range. The authors believe that the platform can be further used in several different applications including lab-on-chip platforms, analytical chemistry for medicine approaches, quantitative cell cultures, and even drug injection into single cells.

Figure 1. The microfluidic device for sub-picoliter volume liquid handling

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Pressure-controlled microfluidic sub-picoliter ultramicro-volume syringes based on integrated micro-nanostructure arrays

Nianzuo Yu, Yongshun Liu, Shuli Wang, Xiaoduo Tang, Peng Ge, Jingjie Nan, Junhu Zhang, and Bai Yang, Lab Chip, 2019, Lab on a Chip Hot Articles

DOI: 10.1039/C9LC00730J

About the Webwriter

Burcu Gumuscu is a researcher in Mesoscale Chemical Systems Group at the University of Twente in the Netherlands. Her research interests include the 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.