Periodic Reporting for period 4 - OSIRIS (Organic Semiconductors Interfaced with Biological Environments) Reporting period: 2022-02-01 to 2022-07-31 Summary of the context and overall objectives of the project Transducing information to and from biological environments is essential for bioresearch, neuroscience and healthcare. There has been recent focus on using organic semiconductors to interface the living world, since their structural similarity to bio-macromolecules strongly favours their biological integration. Versatile applications have been demonstrated – sensing, neural stimulation, transduction of brain activity, and photo-stimulation of cells.However, progress in the organic biosensing and bioelectronics field is limited by poor understanding of the underlying fundamental working principles. Given the complexity of the disordered, hybrid solid-liquid systems of interest, gaining mechanistic knowledge presents a considerable scientific challenge. The objective of OSIRIS was to overcome this challenge with a high-end spectroscopic approach, previously missing from the field. Via spectroscopy, we have targeted relevant processes with high time-resolution, structurally characterized the solid-liquid interface using non-linear optical effects, exploited shifts in the absorption spectra related to interfacial fields, determined nanoscale charge mobility using terahertz spectroscopy and simultaneously measured ionic transport.Specific objectives were:1) To investigate how the properties of organic semiconductors are affected upon exposure to aqueous biological environments. 2) To understand the relevant interfaces between organic semiconductors and aqueous biological environments.3) To study how information is transduced across the interface (ion penetration, optical signals, thermal effects, charge transfer, electric fields). Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far • We have investigated complexes of single-stranded DNA with conjugated polyelectrolytes in solution, showing how the assembly of the two affects the photophysical behaviour of the polymer backbone, and thus establishing structure-property relations for biosensing applications (Chemistry of Materials 2020).• We have studied the excited-state properties and terahertz (THz) conductivity of doped organic thin films (self-doped conjugated polyelectrolytes, PEDOT:PSS, doped small molecule TAPC, doped polymer P3HT), which are important in organic bioelectronics and in particular for organic electrochemical transistors (OECTs). (Advanced Functional Materials 2020, Physical Review Letters 2020, Journal of Physical Chemistry C 2021, 2 more publications in preparation).• We have developed the capacity to prepare and characterize OECTs for bioelectronic applications. In particular, we have developed unique steady-state and time-resolved techniques for in-operando measurements of processes occurring in OECTs, exploring visible, near-infrared, Raman and THz spectroscopy.• We have reported a highly sensitive THz detection scheme to carry out the above OECT in-situ measurements in spite of the strong attenuation of the THz radiation by water present in OECTs (Journal of the Optical Society of America 2020).• We have investigated the electrochemical processes in devices based on PEDOT:PSS (Advanced Functional Materials 2022), P3HT (Materials Horizons 2022), thiophenes with ionic sidechains (publication in preparation), and ProDOT-based polymers (submitted to the Journal of the American Chemical Society). Several follow-up publications are in preparation.• We have interfaced lipid bilayers on the bioelectronic OECT devices, in order to study the effect of membrane integrity on the doping and dedoping dynamics.• We have measured the time-resolved charge transfer dynamics of photoelectrochemical devices following voltage pulses and photoexcitation.• We have set up a non-linear sum-frequency generation (SFG) experiment to study molecular vibrations selectively at the interface of organic conjugated polymer films with water (Optics Letters 2020). Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) • While it has been known for some time that conjugated polyelectrolytes (CPEs) can assemble with biological macromolecules, leading to a strong optical response due to structural changes in the polymer backbone, we managed to gain unprecedented atomistic-level understanding of how single DNA strands impact the conformation of thiophene-based CPEs, allowing to predict which combinations of DNA sequences with specific CPEs yield the largest photophysical changes.• The electronic structure and origin of the optical transitions in doped organic semiconductors have recently been put into question by theoretical work. Our excited-state study on a self-doped CPE has allowed first direct experimental evidence for this new interpretation, which radically changes the understanding of the optoelectronics in those doped systems. • For doped small molecule TAPC, we were able to evidence excited-state charge transfer between cationic TAPC molecules and their neutral neighbors, leading to enhanced conductivity. This brings insight to the debated question of how charges separate from he Coulomb potential of the ionized dopant, highlighting the role of excess energy and delocalization.• We have put together a unique palette of experiments to gain comprehensive insights to the functioning of organic electrochemical transistors (OECTs). In particular, the development and full characterization of a highly sensitive terahertz (THz) detection scheme represent a significant technological advance, that has allowed us to carry out in-operando THz measurements on OECTs, which has not yet been achieved by any other group.• By measuring the electrochemical dedoping and redoping dynamics of PEDOT:PSS at different temperatures, we have determined the full thermodynamic reaction profile of the redox reactions in this most used organic bioelectronic material. We revealed that dedoping is driven by enthalpy, while redoping is driven by entropy and that the reaction rates are determined by the transition state entropy.• We have obtained a full picture of the electrochemical doping of P3HT (a state-of-the-art polymer) in KPF6 electrolyte, using in-operando spectroscopy in different wavelength ranges. We have distinguished the redox species in the ordered and disordered regions of semicrystalline P3HT due to their different optical and Raman signatures. This revealed that bipolarons preferentially form in the disordered regions, which are by themselves not very conductive. Interestingly, these bipolarons still enhance the overall fraction of conductive charge (seen by THz spectroscopy), possibly by helping the transport between ordered regions along tie chains.• We have applied our experimental approach to a variety of materials, including thiophenes with ioniuc sidechains, glycolated ProDOT derivatives, light-responsive systems, and OECTs interfaced with lipid membranes.• We have shown by SFG spectroscopy that the alkyl sidechains of P3HT stand up in air but lie down in water, while hydrophillic sidechains also stand up in water, which can impcact ion peneration and interfacial fields. Illustration: Spectroscopic investigation of organic bioelectronic devices
