Morton Andrew, Murawski Caroline, Deng Yali, Keum Changmin, Miles Gareth B, Tello Javier A, Gather Malte C
Organic Semiconductor Centre, SUPA School of Physics and Astronomy, University of St Andrews, North Haugh, KY16 9SS, St Andrews, UK.
School of Psychology and Neuroscience, University of St Andrews, St Mary's Quad, South Street, KY16 9JP, St Andrews, UK.
Adv Biosyst. 2019 Mar;3(3):e1800290. doi: 10.1002/adbi.201800290. Epub 2019 Jan 16.
Optogenetics, photostimulation of neural tissues rendered sensitive to light, is widely used in neuroscience to modulate the electrical excitability of neurons. For effective optical excitation of neurons, light wavelength and power density must fit with the expression levels and biophysical properties of the genetically encoded light-sensitive ion channels used to confer light sensitivity on cells-most commonly, channelrhodopsins (ChRs). As light sources, organic light-emitting diodes (OLEDs) offer attractive properties for miniaturized implantable devices for in vivo optical stimulation, but they do not yet operate routinely at the optical powers required for optogenetics. Here, OLEDs with doped charge transport layers are demonstrated that deliver blue light with good stability over millions of pulses, at powers sufficient to activate the ChR, CheRiff when expressed in cultured primary neurons, allowing live cell imaging of neural activity with the red genetically encoded calcium indicator, jRCaMP1a. Intracellular calcium responses scale with the radiant flux of OLED emission, when varied through changes in the current density, number of pulses, frequency, and pulse width delivered to the devices. The reported optimization and characterization of high-power OLEDs are foundational for the development of miniaturized OLEDs with thin-layer encapsulation on bioimplantable devices to allow single-cell activation in vivo.
光遗传学，即对经遗传改造而变得对光敏感的神经组织进行光刺激，在神经科学中被广泛用于调节神经元的电兴奋性。为了有效地对神经元进行光激发，光的波长和功率密度必须与用于使细胞具有光敏感性的基因编码光敏感离子通道的表达水平和生物物理特性相匹配——最常见的是通道视紫红质（ChRs）。作为光源，有机发光二极管（OLED）为用于体内光刺激的小型可植入设备提供了吸引人的特性，但它们尚未能在光遗传学所需的光功率下常规运行。在此，展示了具有掺杂电荷传输层的OLED，其在数百万次脉冲中能稳定地发出蓝光，功率足以激活在原代培养神经元中表达时的通道视紫红质CheRiff，从而能够使用红色基因编码钙指示剂jRCaMP1a对神经活动进行活细胞成像。当通过改变施加到设备的电流密度、脉冲数、频率和脉冲宽度来改变时，细胞内钙反应与OLED发射的辐射通量成比例。所报道的高功率OLED的优化和表征是开发具有薄层封装的小型化OLED用于生物可植入设备以实现体内单细胞激活的基础。
