An organic electronic biomimetic neuron enables auto-regulated neuromodulation.
Current therapies for neurological disorders are based on traditional medication and electric stimulation. Here, we present an organic electronic biomimetic neuron, with the capacity to precisely intervene with the underlying malfunctioning signalling pathway using endogenous substances. The fundamental function of neurons, defined as chemical-to-electrical-to-chemical signal transduction, is achieved by connecting enzyme-based amperometric biosensors and organic electronic ion pumps. Selective biosensors transduce chemical signals into an electric current, which regulates electrophoretic delivery of chemical substances without necessitating liquid flow. Biosensors detected neurotransmitters in physiologically relevant ranges of 5-80 µM, showing linear response above 20 µm with approx. 0.1 nA/µM slope. When exceeding defined threshold concentrations, biosensor output signals, connected via custom hardware/software, activated local or distant neurotransmitter delivery from the organic electronic ion pump. Changes of 20 µM glutamate or acetylcholine triggered diffusive delivery of acetylcholine, which activated cells via receptor-mediated signalling. This was observed in real-time by single-cell ratiometric Ca(2+) imaging. The results demonstrate the potential of the organic electronic biomimetic neuron in therapies involving long-range neuronal signalling by mimicking the function of projection neurons. Alternatively, conversion of glutamate-induced descending neuromuscular signals into acetylcholine-mediated muscular activation signals may be obtained, applicable for bridging injured sites and active prosthetics.
Swedish Medical Nanoscience Center, Karolinska Institutet, S-171 77 Stockholm, Sweden; Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden; Laboratory of Organic Electronics, Department of Science and Technology, ITN, Linköping University, S-601 74 Norrköping, Sweden. Electronic address: daniel.simon@liu.se.
Daniel T
DT
Simon
Swedish Medical Nanoscience Center, Karolinska Institutet, S-171 77 Stockholm, Sweden; Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Karin C
KC
Larsson
Acreo Swedish ICT AB, S-602 21 Norrköping, Sweden.
David
D
Nilsson
Swedish Medical Nanoscience Center, Karolinska Institutet, S-171 77 Stockholm, Sweden; Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Gustav
G
Burström
Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Dagmar
D
Galter
Laboratory of Organic Electronics, Department of Science and Technology, ITN, Linköping University, S-601 74 Norrköping, Sweden.
Magnus
M
Berggren
Swedish Medical Nanoscience Center, Karolinska Institutet, S-171 77 Stockholm, Sweden; Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden. Electronic address: agneta.richter.dahlfors@ki.se.
Agneta
A
Richter-Dahlfors
D032701:Biomimetics / Q000295:instrumentation*; D015374:Biosensing Techniques / Q000295:instrumentation*; D003217:Conductometry / Q000295:instrumentation*; D004581:Electronics / Q000295:instrumentation; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005246:Feedback; D005947:Glucose / Q000032:analysis; D016623:Ion Pumps / Q000737:chemistry*; D009474:Neurons / Q000737:chemistry* / Q000502:physiology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D016623:Ion Pumps; D005947:Glucose
Controlled drug release; Neural prosthesis; Neuromodulation; Organic electronic material