PEDOT:PSS: A conductive and flexible polymer for sensor integration in Organ-on-Chip platforms

ConferenciaSensing and stimulating microstructures are necessary to develop more specialized and highly accurate Organ-on-Chip (OOC) platforms. In this paper, we present the integration of a conductive polymer, poly (3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS), on a stretchable membrane, core element of an Heart-on-Chip. The electrical conductivity along with its biocompatibility, high transparency (�����88 %) and mechanical elasticity (�����1.2 GPa) make this material a candidate to develop novel microstructures for electrical monitoring and stimulation of cells in flexible-substrate based OOCs. Microstructures with different shapes and geometries of PEDOT:PSS embedded in a 9 μm-thick Polydimethylsiloxane (PDMS) membrane are developed following a wafer-level fabrication approach. PEDOT:PSS layers between 120 nm and 300 nm are obtained by varying the deposition conditions. The layers are successfully patterned and microstructures with lateral dimensions down to 2 μm. The obtained results indicate that this polymer is a suitable material for microfabrication of sensing and stimulating elements in OOC platforms

An end-user perspective on Organ-on-a-Chip: Assays and usability aspects

Analytical BioScience

Biology-inspired microphysiological systems to advance patient benefit and animal welfare in drug development

The first microfluidic microphysiological systems (MPS) entered the academic scene more than 15 years ago and were considered an enabling technology to human (patho)biology in vitro and, therefore, provide alternative approaches to laboratory animals in pharmaceutical drug development and academic research. Nowadays, the field generates more than a thousand scientific publications per year. Despite the MPS hype in academia and by platform providers, which says this technology is about to reshape the entire in vitro culture landscape in basic and applied research, MPS approaches have neither been widely adopted by the pharmaceutical industry yet nor reached regulated drug authorization processes at all. Here, 46 leading experts from all stakeholders - academia, MPS supplier industry, pharmaceutical and consumer products industries, and leading regulatory agencies - worldwide have analyzed existing challenges and hurdles along the MPS-based assay life cycle in a second workshop of this kind in June 2019. They identified that the level of qualification of MPS-based assays for a given context of use and a communication gap between stakeholders are the major challenges for industrial adoption by end-users. Finally, a regulatory acceptance dilemma exists against that background. This t4 report elaborates on these findings in detail and summarizes solutions how to overcome the roadblocks. It provides recommendations and a roadmap towards regulatory accepted MPS-based models and assays for patients' benefit and further laboratory animal reduction in drug development. Finally, experts highlighted the potential of MPS-based human disease models to feedback into laboratory animal replacement in basic life science research.Toxicolog

Organ-on-chipeissä käytettävien materiaalien bioyhteensopivuus

Organ-on-chippien tavoite on mallintaa ihmisen eri elimiä. Tulevaisuudessa ne voivat toimia vaihtoehtona eläinkokeille, apuna sairauksien tutkinnassa ja lääkkeiden sopivuuden testaamisessa potilaille. Organ-on-chipeissä yhdistyy mikrofluidistiikka, soluviljely ja mikrosysteemit. Sirulle pyritään rakentamaan ympäristö, joka mahdollisimman tarkasti vastaisi solujen ympäristöä kehossa. Teknisten haasteiden johdosta kaksiulotteiset soluviljelmät ovat yleisempiä kuin kolmiulotteiset viljelmät. Organ-on-chipissä on usein käytetty mikrofluidistiikkaa, jonka avulla solujen kasvatusmediumin jatkuva kierto on mahdollista. Sirulle on mahdollista integroida erilaisia solujen stimulointiin tarkoitettuja elementtejä, kuten elektrodeja sekä erilaisia antureita, jotka mahdollistavat solujen kasvun seuraamisen. Solujen toimivuuden kannalta on tärkeää, että organ-on-chipin materiaalit eivät aiheuta soluissa sytotoksista reaktiota ja mahdollistavat niiden normaalin biologisen toiminnan, eli ovat bioyhteensopivia. Bioyhteensopivuutta tutkitaan erilaisin solujen elävyyttä mittaavin testin ja mikroskopian avulla. Bioyhteensopivuuden arvioinnille on määritelty ISO-10933 standardi, mutta se on suunniteltu lääkelaitteiden validointia varten. Tässä työssä esitellään neljä organ-on-chipeissä käytettävää materiaalia: polydimetyylisiloksaani (PDMS), SU-8, polyimidi ja grafeeni sekä tutustutaan niiden bioyhteensopivuuteen ja joihinkin sovelluksiin. PDMS on tällä hetkellä yleisin käytetty materiaali organ-on-chipeissä, mutta se absorboi hydrofobisia molekyylejä, joten se ei sovellu lääketestaukseen. SU-8 ja polyimidi ovat paljon käytettyjä mikroelektromekaanisissa systeemeissä ja niitä hyödynnetään sensoreiden materiaalina ja monimutkaisten muotojen valmistuksessa. Grafeeni on yksi hiilen olomuodoista ja sitä käytetään lisänä sovelluksissa, joissa sähkönjohtavuutta halutaan parantaa. PDMS, polyimidi ja SU-8 eivät pääsääntöisesti aiheuta sytotoksista reaktiota soluissa. Solujen kiinnittyvyys materiaaleille paranee, jos ne päällystetään esimerkiksi kollageenilla tai polydopamiinilla, tai pinta nanokuvioidaan. SU-8 ja polyimidi voivat aiheuttaa sytotoksisen vasteen soluissa, jos niiden paistolämpötila tai paistoaika on ollut riittämätön. Grafeeni ja siihen perustuvien materiaalien sytotoksisuudesta on olemassa ristiriitaisia tutkimustuloksia ja grafeenin vaikutus soluihin riippuu suuresti testattavasta solulinjasta ja grafeenin konsentraatiosta liuoksessa. Etenkin hapetetun grafeenin on havaittu kulkeutuvan solujen sisälle sekä häiritsevän happiradikaalien ja antioksidanttien tasapainoa, johtaen oksitatiiviseen stressiin. Tutkimustulokset grafeenin hapetustason vaikutuksesta bioyhteensopivuuteen ovat myös ristiriitaiset, sillä viitteitä on, että matala hapetustaso sekä lisäisi että vähentäisi materiaalin bioyhteensopivuutta

Small molecule absorption by PDMS in the context of drug response bioassays

Stem cells & developmental biolog

Small molecule absorption by PDMS in the context of drug response bioassays

The polymer polydimethylsiloxane (PDMS) is widely used to build microfluidic devices compatible with cell culture. Whilst convenient in manufacture, PDMS has the disadvantage that it can absorb small molecules such as drugs. In microfluidic devices like "Organs-on-Chip", designed to examine cell behavior and test the effects of drugs, this might impact drug bioavailability. Here we developed an assay to compare the absorption of a test set of four cardiac drugs by PDMS based on measuring the residual non-absorbed compound by High Pressure Liquid Chromatography (HPLC). We showed that absorption was variable and time dependent and not determined exclusively by hydrophobicity as claimed previously. We demonstrated that two commercially available lipophilic coatings and the presence of cells affected absorption. The use of lipophilic coatings may be useful in preventing small molecule absorption by PDMS. (C) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license

Cell Migration According to Shape of Graphene Oxide Micropatterns

Photolithography is a unique process that can effectively manufacture micro/nano-sized patterns on various substrates. On the other hand, the meniscus-dragging deposition (MDD) process can produce a uniform surface of the substrate. Graphene oxide (GO) is the oxidized form of graphene that has high hydrophilicity and protein absorption. It is widely used in biomedical fields such as drug delivery, regenerative medicine, and tissue engineering. Herein, we fabricated uniform GO micropatterns via MDD and photolithography. The physicochemical properties of the GO micropatterns were characterized by atomic force microscopy (AFM), scanning electron microscopy (SEM), and Raman spectroscopy. Furthermore, cell migration on the GO micropatterns was investigated, and the difference in cell migration on triangle and square GO micropatterns was examined for their effects on cell migration. Our results demonstrated that the GO micropatterns with a desired shape can be finely fabricated via MDD and photolithography. Moreover, it was revealed that the shape of GO micropatterns plays a crucial role in cell migration distance, speed, and directionality. Therefore, our findings suggest that the GO micropatterns can serve as a promising biofunctional platform and cell-guiding substrate for applications to bioelectric devices, cell-on-a-chip, and tissue engineering scaffolds.ope

Electrical and microfluidic technologies for organs-on-chips:Mimicking blood-brain barrier and gut tissues

The goal of the research presented in this thesis is to develop new technologies for organs-on-chips to enable direct measurements of cell layer functions and to move towards high-throughput. In this introduction, a brief description is included of the tissues that were mimicked in the organs-on-chips described in this thesis. Next, conventional in vitro setups for mimicking these tissues are discussed as well as the advantages of organs-on-chips over these conventional in vitro models. Then, the most important tests of tissue function are described. Subsequently, the larger framework for the research described in this thesis is sketched and lastly an outline of the thesis is given