Real-time monitoring of biliary transport in precision-cut liver slices

Maciej Grajewski, Gert IJ. Salentijn, Ruby E.H. Karsten, Peter Olinga and Elisabeth Veropoorte

uTAS 2018 and SLAS 2019

Development of a system for monitoring cholestasis development in precision-cut liver slices (PCLS) an ex-vivo tissue model for studying drug toxicity.

Real-time monitoring of biliary transport in precision-cut liver slices

The eLoaD platform endows centrifugal microfluidics with on-disc power and communication

Saraí M. Torres Delgado, Jan G. Korvink, Dario Mager,*

In this paper we present a comprehensive description of the design, fabrication and operation of an electrified Lab-on-a-Disc (eLoaD) system. The smart platform is developed to extend conventional Lab-on-a-Disc applications with an electronic interface, providing additional flow control and sensing capabilities to centrifugal microfluidics platforms. Wireless power is transferred from a Qi-compliant transmitter to the eLoaD platform during rotation. An Arduino-based microcontroller, a Bluetooth communication module, and an on-board SD-card are integrated into the platform. This generalises the applicability of the eLoaD and its modules for performing a wide range of laboratory unit operations, procedures, or diagnostic assays, all controlled wirelessly during spinning. The lightweight platform is fully reusable and modular in design and construction. An interchangeable and non-disposable application disc is fitted with the necessary sensors and/or actuators for a specific assay or experiment to be performed. A particular advantage is the ability to continuously monitor and interact with LoaD experiments, overcoming the limitations of stroboscopy. We demonstrate the applicability of the platform for three sensing experiments involving optical, electrochemical, and temperature detection, and one actuation experiment involving controlled heating/cooling. The complete electronic designs and example programming codes are extensively documented in the supplementary material for easy adaptation.


High-resolution nuclear magnetic resonance spectroscopy in microfluidic droplets

William Hale, Gabriel Rossetto, Rachael Greenhalgh, Graeme Finch and Marcel Utz*

Lab Chip, 2018,18, 3018-3024

A generic approach is presented that allows high-resolution NMR spectroscopy of water/oil droplet emulsions in microfluidic devices. Microfluidic NMR spectroscopy has recently made significant advances due to the design of micro-detector systems and their successful integration with microfluidic devices. Obtaining NMR spectra of droplet suspensions, however, is complicated by the inevitable differences in magnetic susceptibility between the chip material, the continuous phase, and the droplet phases. This leads to broadening of the NMR resonance lines and results in loss of spectral resolution. We have mitigated the susceptibility difference between the continuous (oil) phase and the chip material by incorporating appropriately designed air-filled structures into the chip. The susceptibilities of the continuous and droplet (aqueous) phases have been matched by doping the droplet phase with a Eu3+ complex. Our results demonstrate that this leads to a proton line width in the droplet phase of about 3 Hz, enabling high-resolution NMR techniques.

Probing the kinetics in supramolecular chemistry and molecular assembly by microfluidic-NMR spectroscopy

Hongxun Fang, Yibin Sun, Xinchang Wang, Manvendra Sharma, Zhong Chen, Xiaoyu Cao*, Marcel Utz* and Zhongqun Tian*

Science China Chemistry, 2018

Microfluidic-NMR spectroscopy has been extended to study the kinetics in supramolecular chemistry and molecular assembly. Kinetics of a multicomponent host-guest supramolecular system containing viologen derivatives, β-cyclodextrins and cucurbit [7]urils are studied by a PMMA based microfluidic chip combined with a dedicated transmission line probe for NMR detection. By combining microfluidic technology with NMR spectroscopy, the amount of material required for a full kinetic study could be minimized. This is crucial in supramolecular chemistry, which often involves highly sophisticated and synthetically costly building blocks. The small size of the microfluidic structure is crucial in bringing the time scale for kinetic monitoring down to seconds. At the same time, the transmission line NMR probe provides sufficient sensitivity to work at low (2 mM) concentrations.

Wirelessly powered and remotely controlled valve-array for highly multiplexed analytical assay automation on a centrifugal microfluidic platform

Saraí M. Torres Delgado, David J. Kinahan, Lourdes Albina Nirupa Julius, Adam Mallette, David Sáenz Ardila, Rohit Mishra, Celina M. Miyazaki, Jan G. Korvink, Jens Ducrée, Dario Mager

Biosensors and Bioelectronics, 2019

In this paper we present a wirelessly powered array of 128 centrifugo-pneumatic valves that can be thermally actuated on demand during spinning. The valves can either be triggered by a predefined protocol, wireless signal transmission via Bluetooth, or in response to a sensor monitoring a parameter like the temperature, or homogeneity of the dispersion. Upon activation of a resistive heater, a low-melting membrane (Parafilm™) is removed to vent an entrapped gas pocket, thus letting the incoming liquid wet an intermediate dissolvable film and thereby open the valve. The proposed system allows up to 12 heaters to be activated in parallel, with a response time below 3 s, potentially resulting in 128 actuated valves in under 30 s. We demonstrate, with three examples of common and standard procedures, how the proposed technology could become a powerful tool for implementing diagnostic assays on Lab-on-a-Disc. First, we implement wireless actuation of 64 valves during rotation in a freely programmable sequence, or upon user input in real time. Then, we show a closed-loop centrifugal flow control sequence for which the state of mixing of reagents, evaluated from stroboscopically recorded images, triggers the opening of the valves. In our last experiment, valving and closed-loop control are used to facilitate centrifugal processing of whole blood.

Murine precision-cut liver slices as a disease model to predict drug-induced cholestasis

Ruby E.H. Karsten. Maciej Grajewski, Gert IJ. Salentijn, Viktoriia Starokozkho, Elisabeth Verpoorte, Peter Olinga

University of Groningen

SLAS 2018

Develop a disease model to study drug-induced cholestasis in precision-cut liver slices (PCLS) in real time

Murine precision-cut liver slices as a disease model to predict drug-induced cholestasis