dr. A. Savva

1. Single-Component Electroactive Polymer Architectures for Non-Enzymatic Glucose Sensing
   Kousseff, Christina J.; Wustoni, Shofarul; Silva, Raphaela K. S.; Lifer, Ariel; Savva, Achilleas; Frey, Gitti L.; Inal, Sahika; Nielsen, Christian B.;
   Advanced Science,
   Volume n/a, Issue n/a, pp. 2308281, 2024. DOI: https://doi.org/10.1002/advs.202308281
   
   Keywords: ...

   electropolymerization, glucose sensor, organic bioelectronics, organic electrochemical transistors, PEDOT.
   
   
   Abstract: ...

   Abstract Organic mixed ionic-electronic conductors (OMIECs) have emerged as promising materials for biological sensing, owing to their electrochemical activity, stability in an aqueous environment, and biocompatibility. Yet, OMIEC-based sensors rely predominantly on the use of composite matrices to enable stimuli-responsive functionality, which can exhibit issues with intercomponent interfacing. In this study, an approach is presented for non-enzymatic glucose detection by harnessing a newly synthesized functionalized monomer, EDOT-PBA. This monomer integrates electrically conducting and receptor moieties within a single organic component, obviating the need for complex composite preparation. By engineering the conditions for electrodeposition, two distinct polymer film architectures are developed: pristine PEDOT-PBA and molecularly imprinted PEDOT-PBA. Both architectures demonstrated proficient glucose binding and signal transduction capabilities. Notably, the molecularly imprinted polymer (MIP) architecture demonstrated faster stabilization upon glucose uptake while it also enabled a lower limit of detection, lower standard deviation, and a broader linear range in the sensor output signal compared to its non-imprinted counterpart. This material design not only provides a robust and efficient platform for glucose detection but also offers a blueprint for developing selective sensors for a diverse array of target molecules, by tuning the receptor units correspondingly.
   
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2. Organic Mixed Ionic–Electronic Conductors Based on Tunable and Functional Poly(3,4-ethylenedioxythiophene) Copolymers
   Wu, Jiaxin; Gu, Modi; Travaglini, Lorenzo; Lauto, Antonio; Ta, Daniel; Wagner, Pawel; Wagner, Klaudia; Zeglio, Erica; Savva, Achilleas; Officer, David; Mawad, Damia;
   ACS Applied Materials \& Interfaces,
   Volume 16, Issue 22, pp. 28969-28979, 2024. PMID: 38778796. DOI: 10.1021/acsami.4c03229
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3. Photo-Chemical Stimulation of Neurons with Organic Semiconductors
   Savva, Achilleas; Hama, Adel; Herrera-López, Gabriel; Schmidt, Tony; Migliaccio, Ludovico; Steiner, Nadia; Kawan, Malak; Fiumelli, Hubert; Magistretti, Pierre J.; McCulloch, Iain; Baran, Derya; Gasparini, Nicola; Schindl, Rainer; Głowacki, Eric D.; Inal, Sahika;
   Advanced Science,
   Volume 10, Issue 31, pp. 2300473, 2023. DOI: https://doi.org/10.1002/advs.202300473
   
   Keywords: ...

   non-fullerene acceptors, organic bioelectronics, photo-stimulation.
   
   
   Abstract: ...

   Abstract Recent advances in light-responsive materials enabled the development of devices that can wirelessly activate tissue with light. Here it is shown that solution-processed organic heterojunctions can stimulate the activity of primary neurons at low intensities of light via photochemical reactions. The p-type semiconducting polymer PDCBT and the n-type semiconducting small molecule ITIC (a non-fullerene acceptor) are coated on glass supports, forming a p–n junction with high photosensitivity. Patch clamp measurements show that low-intensity white light is converted into a cue that triggers action potentials in primary cortical neurons. The study shows that neat organic semiconducting p–n bilayers can exchange photogenerated charges with oxygen and other chemical compounds in cell culture conditions. Through several controlled experimental conditions, photo-capacitive, photo-thermal, and direct hydrogen peroxide effects on neural function are excluded, with photochemical delivery being the possible mechanism. The profound advantages of low-intensity photo-chemical intervention with neuron electrophysiology pave the way for developing wireless light-based therapy based on emerging organic semiconductors.
   
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4. 3D organic bioelectronics for electrical monitoring of human adult stem cells
   Savva, Achilleas; Saez, Janire; Withers, Aimee; Barberio, Chiara; Stoeger, Verena; Elias-Kirma, Shani; Lu, Zixuan; Moysidou, Chrysanthi-Maria; Kallitsis, Konstantinos; Pitsalidis, Charalampos; Owens, Róisín M.;
   Mater. Horiz.,
   Volume 10, pp. 3589-3600, 2023. DOI: 10.1039/D3MH00785E
   
   Abstract: ...

   Three-dimensional in vitro stem cell models have enabled a fundamental understanding of cues that direct stem cell fate. While sophisticated 3D tissues can be generated{,} technology that can accurately monitor these complex models in a high-throughput and non-invasive manner is not well adapted. Here we show the development of 3D bioelectronic devices based on the electroactive polymer poly(3{,}4-ethylenedioxythiophene)-poly(styrenesulfonate)–(PEDOT:PSS) and their use for non-invasive{,} electrical monitoring of stem cell growth. We show that the electrical{,} mechanical and wetting properties as well as the pore size/architecture of 3D PEDOT:PSS scaffolds can be fine-tuned simply by changing the processing crosslinker additive. We present a comprehensive characterization of both 2D PEDOT:PSS thin films of controlled thicknesses{,} and 3D porous PEDOT:PSS structures made by the freeze-drying technique. By slicing the bulky scaffolds we generate homogeneous{,} porous 250 μm thick PEDOT:PSS slices{,} constituting biocompatible 3D constructs able to support stem cell cultures. These multifunctional slices are attached on indium-tin oxide substrates (ITO) with the help of an electrically active adhesion layer{,} enabling 3D bioelectronic devices with a characteristic and reproducible{,} frequency dependent impedance response. This response changes drastically when human adipose derived stem cells (hADSCs) grow within the porous PEDOT:PSS network as revealed by fluorescence microscopy. The increase of cell population within the PEDOT:PSS porous network impedes the charge flow at the interface between PEDOT:PSS and ITO{,} enabling the interface resistance (R1) to be used as a figure of merit to monitor the proliferation of stem cells. The non-invasive monitoring of stem cell growth allows for the subsequent differentiation 3D stem cell cultures into neuron like cells{,} as verified by immunofluorescence and RT-qPCR measurements. The strategy of controlling important properties of 3D PEDOT:PSS structures simply by altering processing parameters can be applied for development of a number of stem cell in vitro models as well as stem cell differentiation pathways. We believe the results presented here will advance 3D bioelectronic technology for both fundamental understanding of in vitro stem cell cultures as well as the development of personalized therapies.
   
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