The Fabrication of Microfluidics, 3D Cell Culture, Organ-on-a-Chip

Category: Blog,From Academia
Dec 07, 2020

In this issue, we included three latest publications focusing on alternative materials for the fabrication of microfluidics or organ-on-a-chip, 3D cell culturing microfluidic devices, and microfluidics using digital light processing. “From Academia” features recent, relevant, close to commercialization academic publications. Subjects include but not limited to healthcare 3D printing, 3D bioprinting, and related emerging technologies.

Email: Rance Tino ([email protected]) if you want to share relevant academic publications with us.

Beyond Polydimethylsiloxane: Alternative Materials for Fabrication of Organ-on-a-Chip Devices and Microphysiological Systems

Authored by Scott B. Campbell, Qinghua Wu, Joshua Yazbeck, Chuan Liu, Sargol Okhovatian, and Milica Radisic. ACS Biomaterials Science & Engineering. 11 August 2020

Abstract: 

Polydimethylsiloxane (PDMS) is the predominant material used for organ-on-a-chip devices and microphysiological systems (MPSs) due to its ease-of-use, elasticity, optical transparency, and inexpensive microfabrication.

However, the absorption of small hydrophobic molecules by PDMS and the limited capacity for high-throughput manufacturing of PDMS-laden devices severely limit the application of these systems in personalized medicine, drug discovery, in vitro pharmacokinetic/pharmacodynamic (PK/PD) modeling, and the investigation of cellular responses to drugs.

Consequently, the relatively young field of organ-on-a-chip devices and MPSs is gradually beginning to make the transition to alternative, nonabsorptive materials for these crucial applications.

This review examines some of the first steps that have been made in the development of organ-on-a-chip devices and MPSs composed of such alternative materials, including elastomers, hydrogels, thermoplastic polymers, and inorganic materials. It also provides an outlook on where PDMS-alternative devices are trending and the obstacles that must be overcome in the development of versatile devices based on alternative materials to PDMS.

Fabrication of Microfluidics, Applications, Organ-on-a-Chip Examples of elastomer-based microfluidic devices. Copyright ACS Biomaterials Science & Engineering
Examples of elastomer-based microfluidic devices. Copyright ACS Biomaterials Science & Engineering

Characterising a PDMS based 3D cell culturing microfluidic platform for screening chemotherapeutic drug cytotoxic activity

Authored by M. Ibrahim Khot, Mark A. Levenstein, Greg N. de Boer, Gemma Armstrong, Thomas Maisey, Hafdis S. Svavarsdottir, Helen Andrew, Sarah L. Perry, Nikil Kapur & David G. Jayne, Nature Scientific Reports. 28 September 2020 

Fabrication of Microfluidics, Applications, Organ-on-a-Chip (A) Photographic image of the microfluidic device with a blue dye flowing through device and over the 3D spheroid culturing wells. Scalebar = 1 cm. (B) Transillumination microscopic image of the 3D cell culturing wells in the center of PDMS chip which could accommodate the simultaneous culturing of twenty-five 3D spheroids in a 5 × 5 array. Scalebar = 500 μm. Copyright. Nature Scientific Reports
(A) Photographic image of the microfluidic device with a blue dye flowing through device and over the 3D spheroid culturing wells. Scalebar = 1 cm. (B) Transillumination microscopic image of the 3D cell culturing wells in the center of PDMS chip which could accommodate the simultaneous culturing of twenty-five 3D spheroids in a 5 × 5 array. Scalebar = 500 μm. Copyright. Nature Scientific Reports

Abstract: 

Three-dimensional (3D) spheroidal cell cultures are now recognised as better models of cancers as compared to traditional cell cultures. However, established 3D cell culturing protocols and techniques are time-consuming, manually laborious and often expensive due to the excessive consumption of reagents.

Microfluidics allows for traditional laboratory-based biological experiments to be scaled down into miniature custom fabricated devices, where cost-effective experiments can be performed through the manipulation and flow of small volumes of fluid. In this study, we characterize a 3D cell culturing microfluidic device fabricated from a 3D printed master. HT29 cells were seeded into the device and 3D spheroids were generated and cultured through the perfusion of cell media. Spheroids were treated with 5-Fluorouracil for five days through continuous perfusion and cell viability was analyzed on-chip at different time points using fluorescence microscopy and Lactate dehydrogenase (LDH) assay on the supernatant.

Increasing cell death was observed in the HT29 spheroids over the five-day period. The 3D cell culturing microfluidic device described in this study permits on-chip anti-cancer treatment and viability analysis and forms the basis of an effective platform for the high-throughput screening of anti-cancer drugs in 3D tumor spheroids.

A) Transillumination microscopic image and (B) spheroid diameter measurements of HT29 cells in suspension that were seeded onto the PDMS flow chips and cultured under static conditions for 7 days forming uniform sized spheroids. Data shown represent means with standard deviation of 3 independent experiments (3 replicates per experiment). Images are representative of at least 3 independent experiments. Copyright. Nature Scientific Reports
A) Transillumination microscopic image and (B) spheroid diameter measurements of HT29 cells in suspension that were seeded onto the PDMS flow chips and cultured under static conditions for 7 days forming uniform sized spheroids. Data shown represent means with standard deviation of 3 independent experiments (3 replicates per experiment). Images are representative of at least 3 independent experiments. Copyright. Nature Scientific Reports

Fabrication and Functionalization of 3D Printed Polydimethylsiloxane‐Based Microfluidic Devices Obtained through Digital Light Processing

Authored by Gustavo Gonzalez  Annalisa Chiappone  Kurt Dietliker  Candido Fabrizio Pirri  Ignazio Roppolo. Advanced Material Technologies. 29 July 2020

Fabrication of Microfluidics, Applications, Organ-on-a-Chip CAD design illustration and photographs of different microfluidic chips. a) 3D printed microfluidic chip with an s‐shaped channel of 800 µm of diameter, where the channel is filled with green colored water, b) Two 3D printed wells connected by a 1 × 1 mm2 square section channel, c) Trapezoidal 3D printed microfluidic chip with a 1 × 1 mm2 channel square section, d) Photograph of the two 3D printed 96‐wells showing the transparency of the bottom with 500 µm thickness, e) A 3D printed strip (20 × 5 × 1 mm3), showing the excellent stretchability of the material when wrapped around a 3 mm diameter cylinder. Photograph (10×) of the smallest microchannel achieved in f) XY‐plane and g) Z‐axe. Copyright. Advanced Material Technologies
CAD design illustration and photographs of different microfluidic chips. a) 3D printed microfluidic chip with an s‐shaped channel of 800 µm of diameter, where the channel is filled with green colored water, b) Two 3D printed wells connected by a 1 × 1 mm2 square section channel, c) Trapezoidal 3D printed microfluidic chip with a 1 × 1 mm2 channel square section, d) Photograph of the two 3D printed 96‐wells showing the transparency of the bottom with 500 µm thickness, e) A 3D printed strip (20 × 5 × 1 mm3), showing the excellent stretchability of the material when wrapped around a 3 mm diameter cylinder. Photograph (10×) of the smallest microchannel achieved in f) XY‐plane and g) Z‐axe. Copyright. Advanced Material Technologies

Abstract: 

This work reports the preparation and 3D printing of a custom‐made photopolymer based on acrylate‐polydimethylsiloxane (PDMS), for the fabrication of complex‐shaped 3D printed microfluidic chips.

By selecting and combining the proper materials during the preparation of the resins along with the freedom of design of light‐based 3D printers, 3D microfluidic PDMS‐like chips are obtained with excellent optical features, high chemical stability, and good mechanical properties.

Furthermore, taking advantage of unreacted functional groups exposed on the sample’s surface after the 3D printing step, the surface properties of the devices are easily and selectively modified during the post-curing step through UV‐induced grafting polymerization techniques, giving an added value to the printed devices in terms of surface treatment compared to conventional methods.

The 3D printing of the PDMS‐based resins developed here may potentially transform the fabrication methodology of PDMS microfluidic devices by decreasing manufacturing costs and time, allowing the production of complex‐shaped and truly 3D microdevices.

Fabrication of Microfluidics, Applications, Organ-on-a-Chip a) Contact angle measurement and b) ATR‐FTIR absorption spectra of TRAD samples after 1, 5, and 10 min of UV‐induced grating surface modification. Copyright. Advanced Material Technologies
a) Contact angle measurement and b) ATR‐FTIR absorption spectra of TRAD samples after 1, 5, and 10 min of UV‐induced grating surface modification. Copyright. Advanced Material Technologies

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