Symposium EP02—Photonic Materials and Devices for Biointerfaces

Flexible electronics which can be bent, folded and/or stretched, have been applied to various applications, such as biomedical implants and wearable devices, due to their thin structure to facilitate less invasive clinical operations. Flexible devices combined with optoelectronic systems extend to a range of applications such as biomedical stimulations and recordings using light sources, especially as optogenetics. Because light is the primary stimulation tool for optogenetics, optoelectronics benefit from using transparent devices by precisely matched exposing light on the recording site through transparent electrodes. Recently, many research studies have shown that graphene is an excellent candidate as a recording electrode due to its excellent electrical/thermal conductivity, transferability, and mechanical properties. Furthermore, the biocompatibility and broad-wavelength transparency from the ultraviolet (UV) to the infrared radiation (IR) spectrum of graphene make it ideal for the replacement of metal counterparts in optogenetics stimulations, recordings, and imaging applications. Our preliminary results indicate a viable approach combining a hybrid optoelectrical system with light emitting diodes (LEDs) and graphene to fabricate an implantable optogenetics system capable of simultaneous stimulation and recording. However, in our previous work, a laser was used as the light source for neural stimulation externally. Graphene devices without an internally mounted light source are not capable of operating under fully implanted condition. In this work, we built a multifunctional implantable system utilizing nitride-based microscale light emitting diodes (LEDs) vertically stacked on top of graphene electrodes through which light can pass through, enabling synchronous stimulation and recording on an electrocorticogram (ECoG) system utilizing transparent graphene. As such, this study demonstrates graphene electrodes integrated with high-performance flexible optoelectronics devices in thin-film and flexible platform has unique applications in multifunctional optogenetics systems for various clinical operations. Prospective studies will examine the effects and impact of hybrid optoelectronics on the surface of the animal tissue and performing simple animal behavioral experiments.
Acknowledgment: The work was supported by ARO (W911NF-14-1-0652) and partly by DARPA (N66001-17-2-4010).

Although recent efforts in materials development, device designs, and fabrication strategies have resulted in meaningful progresses to the goal of high performance soft implantable bioelectronics, significant challenges still remain. In the first part of this presentation, we report our recent achievement in a ultrathin high-density curved image sensor (CurvIS) array for soft retinal prosthesis. The ultrathin image sensors use a heterostructure of inherently soft 2D materials (MoS2 and graphene) and employ ultrathin and strain-isolating array designs for the human-eye-inspired hemispherically curved design. This high-density soft CurvIS array with the single-lens optics successfully acquires pixelated images without optical aberration and infrared noises, whose potential for appliction to soft subretinal prosthesis was proved through the animal experiment. We then briefly report the recent achievement in the biodegradable drug delivery device for brain tumor treatment. The integration of wireless sensing and actuation function to the biodegradable drug delivery device enables high therapeutic efficacy with long term biocompatibility.

Long-term in vivo multimodal studies combining 2-photon microscopy, optogenetics and electrophysiology are essential for investigating functions of neuronal circuits with high resolution and precision. Graphene is a unique neural interface material enabling cross-talk free integration of electrical and optical recording and stimulation techniques in the same experiment. In addition to optical transparency, graphene also offers other desirable properties such as ultra-flexibility, high conductivity and biocompatibility. To date, graphene-based microelectrode arrays have been demonstrated in various multi-modal acute experiments involving electrophysiological sensing or stimulation, optical imaging and optogenetics stimulation [1-3]. However, understanding chronic reliability of graphene-based transparent interfaces is very important to expand the use of this technology for long-term behavioral studies with animal models. In this work, we investigate chronic durability of transparent graphene electrodes fabricated on polyethylene terephthalate (PET) and SU-8 substrates using in vitro accelerated aging tests. We present our results on simultaneous 2-photon imaging and electrical recording in chronically implanted transgenic mice over the course of two months.

References:
[1] Thunemann, M., Lu, Y., Liu, X., Kilic, K., Desjardins, M., Vandenberghe, Sadegh, S., Saisan, P.A., Cheng, Q., Weldy, K.L., Lyu, H., Djurovic, S., Andreassen, O.A., Dale, A.M., Devor, A., & Kuzum, D. Deep 2-photon imaging and artifact-free optogenetics through transparent graphene microelectrode arrays. Nature Communications, 9(1). doi:10.1038/s41467-018-04457-5 (2018).
[2] Liu, X., Lu, Y., Iseri, E., Shi, Y., & Kuzum, D. A Compact Closed-Loop Optogenetics System Based on Artifact-Free Transparent Graphene Electrodes. Frontiers in Neuroscience, 12. doi:10.3389/fnins.2018.00132 (2018).
[3] Kuzum, D., Takano, H., Shim, E., Reed, J. C., Juul, H., Richardson, A. G., M., Vries, J.D., Bink, H., Dichter, M.A., Lucas, T.H., Coulter, D.A., Cubukcu, E., & Litt, B. Transparent and flexible low noise graphene electrodes for simultaneous electrophysiology and neuroimaging. Nature Communications, 5(1). doi:10.1038/ncomms6259 (2014).

One of the most important mission in wearable electronics is to devise thin, soft, stretchable electronics to circumvent fundamental limitation between soft tissues and rigid electronics. However, progress is hampered by non-trivial engineering, materials, biological, energy systems and data science challenges. The most fundamental of these is failure of the soft/rigid material interface due to mismatching Young's moduli, which limits stretchability and durability of current systems. At the same time, wearable electronic devices are required to be highly biocompatible without fouling and immune responses. Utimately, they could become parts of our organs, enabling true remote biodiagnostics anytime and anywhere.

One-dimensional (1D) nanomaterials should be a pathway to achieve these unique features simultaneously, owing to their intrinsically high-aspect-ratio that enables the construction of conductive percolation network with small amount of material usage while maintaining high optoelectronic performance. Moreover, 1D nanostructures have better mechanical elasticity than corresponding bulk materials or sphere-like nanoparticles and this is a key requirement for designing electronic skin materials by circumventing material delamination and/or cracking. Here we show that standing enokitake-like gold-nanowire-based films chemically bonded to an elastomer can be stretched up to 900% and are highly durable, with >93% conductivity recovery even after 2000 stretching/releasing cycles to 800% strain. this is attributed to standing enokitake-like nanowire structures, vertically aligned configuration, and strong chemical bonding interactions between standing nanowire films and elastomeric substrates. Consequently, our gold nanowire thin film offers an effective and appealing platform for highly stretchable and multifunctional electronic skin system including stretchable interconnects, location- and sharpness- specific sensors, stretchable transistors and energy devices. We believe our technology showed great promise for future wearable and skin-conformal electronics in bio-monitoring and soft robotic applications.

Flexible organic electronics have attracted considerable attention over the past decade. Stretchable electronics represent another type of optoelectronic devices that are intrinsically elastic, that is they are foldable, twistable, and stretchable while maintaining performance, integrity and durability. Incorporated into devices, properly designed stretchable materials may result in more robust devices under bending and strain compared to flexible but not stretchable materials. For intrinsically stretchable electronics, it is desirable to have intrinsically stretchable materials, ranging from stretchable conductors, stretchable dielectric to stretchable semiconductors. In this talk, I will present various molecular design concepts for realizing stretchable electronic polymers without compromising electronic properties. Their applications in bioelectronics will also be presented.

Wearable bioelectronic devices rely on oxidoreductase enzymes and have already demonstrated considerable promise for on-body applications ranging from highly selective non-invasive biomarker monitoring to epidermal energy harvesting. Critical to such progress is the judicious design of the enzyme-electronic interface, along with flexible platforms with mechanical properties similar to those of biological tissues. Such devices require special attention to the enzyme-electronic interface and to several considerations related to wearable applications, such as mechanical properties (flexibility and stretchability), operational stability in different biofluids and under changing conditions (e.g., pH, temperature), biofouling, selectivity, and low target concentrations. Keeping these requirements in mind, our group has pioneered a variety of wearable biocatalytic sensors and biofuel cells devices. By leveraging the advantages of biocatalysis, electrochemistry, and flexible electronics, and addressing key challenges, wearable bioelectronic devices could have a tremendous impact on diverse biomedical, fitness and defense fields.

Among various pressure sensors, transduction mechanisms, piezoresistive, capacitive, triboelectric, and piezoelectric effects are generally considered for converting tactile stimuli into electrical signals.^1,2 Owing to the fast response time and higher sensitivity, piezoelectric pressure sensors (PEPS) are the most useful for the detection of full-range human activities. It has been found that pressure sensor based artificial electronic skin (e-skin) can mimic the human skin and detects subtle pressure (1 Pa–1 kPa). A broad range of applications is expected to be implemented such as wearable health care systems, human–machine interfacing devices, artificial intelligence and prosthetic skin. Nevertheless, piezoelectric materials with adequate flexibility, light weight, ease of large-area processing, low cost and environmental safety are attractive but several issues are remaining for next-generation pressure/force sensors and mechanical energy harvesters. Recent advances on PEPS development is primarily focused on varies types of inorganic and semiconducting piezoelectric materials such as, barium titanate (BaTiO₃), zinc oxide (ZnO), zinc sulfide (ZnS) and lead zirconate titanate (PZT).² In spite of their superior electromechanical responses, the brittleness and toxic properties limit their implementation in wide range of biomedical and flexible electronics applications. On the other hand, natural piezoelectric materials are not yet extensively investigated as an e-skin for measuring and quantifying human physiological signal.²
In this context, we have developed human skin interactive self-powered piezoelectric biomaterials based e-skin (Bio-e-skin) which can detect and discriminate acute human physiological signals such as low frequency as subtle as wrist pulse and even intra-body pressures such as intraocular and intracranial pressure, to relatively high frequency dynamic human motions such as movements of synovial joints of wrist, elbow, knee and finger bending. Natural bio-polymers such as, collagen, chitin, gelatin and cellulose were found to possesses superior mechanosensitivity which was sufficient to fabricate self-powered wearable bio-e-skin that can mimic spatiotemporal human perception and monitors real-time human physiological signals in non-invasive rational strategy. In addition, the bio-skins are found to generate superior output power density which is sufficient to operate the commercial consumer electronics. These observations suggest that fabricated bio-e-skins could eventually find a wide range of applications in autonomous epidermal electronics, implantable medical device, surgery, e-healthcare monitoring, in vitro and in vivo diagnostics apart from its broad range applications in the field of self-powered personal portable electronic devices.^3-5
References
1. Z. L. Wang, J. Song, Science 2006, 312, 242.
2. F. R. Fan, W. Tang, Z. Lin Wang, Adv. Mater., 2016, 28, 4283–4305.
3. S. K.Ghosh, D.Mandal, Appl. Phys. Lett., 2016, 109, 103701.
4. S. K. Ghosh, D. Mandal, Nano Energy, 2016, 28, 356–365.

Recently emerging classes of battery free, ultrasmall¹, fully implantable devices for optogenetic neuromodulation² eliminate physical tethers associated with bulky head-stages and batteries in alternative wireless technologies and conventional setups by leveraging cellular scale light emitting diodes on flexible injectable filaments as light sources³. These highly miniaturized systems enable untethered, operation for behavioral studies that eliminate motion constraints and enable new experimental paradigms in a range of complex 3D environments and contexts (e.g. social interactions) that cannot be explored with conventional technologies. These devices are, however, purely passive in their design, thereby precluding any form of active control or programmability, resulting in limitations when investigating circuit dynamics where independent operation of multiple light sources with precise active control is needed. Here we present a series of important concepts that enable controlled device operation, independent of position and angle relative to the experimental arena, with advanced wireless power harvesting capabilities and full user-programmability over multiple devices. This level of functionality is demonstrated in integrated platforms that are compatible with noninvasive imaging technologies such as computed tomography and magnetic resonance imaging and have sizes and weights not significantly larger than those of previous, passive systems. The resulting devices qualitatively expand options in brain tissue illumination for optogenetic neuromodulation and multimodal operation, with broad potential applications in neuroscience research, with specific advances in precise dissection of neural circuit function during unconstrained behavioral studies.


1 V. K. Samineni, J. Yoon, K. E. Crawford, Y. R. Jeong, K. C. McKenzie, G. Shin, Z. Xie, S. S. Sundaram, Y. Li, M. Y. Yang, J. Kim, D. Wu, Y. Xue, X. Feng, Y. Huang, A. D. Mickle, A. Banks, J. S. Ha, J. P. Golden, J. A. Rogers, and R. W. I. Gereau, PAIN 158,2017).
2 G. Shin, A. M. Gomez, R. Al-Hasani, Y. R. Jeong, J. Kim, Z. Q. Xie, A. Banks, S. M. Lee, S. Y. Han, C. J. Yoo, J. L. Lee, S. H. Lee, J. Kurniawan, J. Tureb, Z. Z. Guo, J. Yoon, S. I. Park, S. Y. Bang, Y. Nam, M. C. Walicki, V. K. Samineni, A. D. Mickle, K. Lee, S. Y. Heo, J. G. McCall, T. S. Pan, L. Wang, X. Feng, T. I. Kim, J. K. Kim, Y. H. Li, Y. G. Huang, R. W. Gereau, J. S. Ha, M. R. Bruchas, and J. A. Rogers, Neuron 93,2017).
3 T. I. Kim, J. G. McCall, Y. H. Jung, X. Huang, E. R. Siuda, Y. Li, J. Song, Y. M. Song, H. A. Pao, R. H. Kim, C. Lu, S. D. Lee, I. S. Song, G. Shin, R. Al-Hasani, S. Kim, M. P. Tan, Y. Huang, F. G. Omenetto, J. A. Rogers, and M. R. Bruchas, Science 340,2013).

On-skin sensors have attractive much attention as the next-generation wearable devices, because the conformal contact on human skin enables accurate and continuous detection of physiological signals. One of the most important technologies to improve usability of on-skin sensors is a power source to continuously supply electricity to health-monitoring systems. In this talk, we will report on recent progresses of ultraflexible organic photovoltaic cells for applications to wearable sensors. First, ultraflexible organic power sources that can be wrapped around an object have been developed with mechanical and thermal stability in long-term operation. Then, the integration of these power sources with functional electric devices including sensors has been achieved.

Recent studies have demonstrated that in addition to biochemical and genetic interactions, cellular systems also respond to biophysical cues, such as electrical, thermal, and mechanical signals. However, we only have limited tools that can introduce localized physical stimuli and/or sense cellular responses with high spatiotemporal resolution. Inorganic semiconductors display a spectrum of physical properties and offer the possibility of numerous device applications. My group integrates material science with biophysics to study several semiconductor-based biointerfaces. In this talk, I will first pinpoint domains where semiconductor properties can be leveraged for biointerface studies, providing a sample of numbers in semiconductor-based biointerfaces. Next, I will present a few recent studies from our lab and highlight key biophysical mechanisms underlying the non-genetic optical modulation interfaces. In particular, I will present a biology-guided two-step design principle for establishing tight intra-, inter-, and extracellular silicon-based interfaces in which silicon and the biological targets have matched mechanical properties and efficient signal transduction. Finally, I will discuss new materials and biological targets that could catalyze future advances.

Organic electronic devices, apart from consumer applications, are presently paving the path for key applications at the interface between electronics and biology. In such applications, organic polymers are very attractive candidates, due to their distinct properties of mechanical flexibility, self-healing and mixed conduction.
My group investigated the processing conditions leading to high electrical conductivity, long-term stability in aqueous media as well as robust mechanical properties of the conducting polymer poly(3,4-ethylenedioxythiophene) doped with polystyrenesulfonate (PEDOT:PSS) [1-3].We have demonstrated that stretchable PEDOT:PSS films can be achieved by adding a fluorosurfactant to the film processing mixture and by pre-stretching the substrate during film deposition. We have achieved patterning of organic materials on a wide range of substrates, using orthogonal lithography and pattern transfer [4-5]. Recently we have discovered that PEDOT:PSS films can be rapidly healed with water drops after being damaged with a sharp blade [6] or show autonomous self-healing if processed in presence of certain additives.
My talk will deal with processing, characterization and patterning of conducting polymer films and devices for flexible, stretchable and healable electronics. I will particularly focus on the strategies to achieve films with optimized electrical conductivity and mechanical properties, on unconventional micro patterning on flexible and stretchable substrates, on the different routes to achieve films stretchability and self-healing.

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The optofluidic bio-laser is an emerging technology in biosensing and imaging. In contrast to traditional fluorescence based measurement, lasing emission is used as the sensing signal, which has strong intensity, threshold behavior, and narrow linewidth, and is free of background. In this presentation, I will first discuss the principle of optofluidic bio-lasers. Then I will discuss three applications with bio-lasers: (1) cellular analysis using cell laser array; (2) intra-cellular laser probes; (3) tissue analysis for cancer diagnosis; (4) neural network monitoring; and (5) ultrasound modulated lasers.

I will present our work on new micro- and nano-photonic devices for studying cell biology and small animals. Our lab is most well-known for the Guinness World Record invention of the biological laser [1]. By inserting sub-µm sized lasers into live cells, we tag and track individual cells in large cell populations and over extended periods of time [2]. We are currently developing this further to perform in vivo intracellular sensing and cell tracking, e.g. in the heart of zebrafish.

Beyond these unique lasers, my lab develops an implantable high-resolution light source for advanced optogenetics studies. Again, miniaturization of photonic devices to sub-cellular dimensions is the key challenge. Organic light-emitting diodes (OLEDs) are highly attractive in this context, in particular due to their low toxicity, mechanical flexibility, high brightness, and ability to provide patterned illumination at very high spatial resolution. OLED microarrays containing >100,000 individual OLED pixels with µm dimensions are used for all-optical control of cell behaviour [3].

[1] M.C. Gather and S.H. Yun, Nature Photonics 5, 406-410 (2011).
[2] M. Schubert et al., Nano Letters, 5647 (2015); M. Schubert et al., Scientific Reports, 40877 (2017); A.H. Fikouras et al., Nature Communications (in press).
[3] A. Steude et al., Advanced Materials 27, 7657-7661 (2015); A. Steude et al., Science Advances 2, e1600061 (2016); A. Morton et al., Scientific Reports 6, 31117 (2016)

Accurate and non-invasive techniques allowing for temperature measurements at the nanoscale have widely spread out with the major development of nanotechnologies and, more specifically, of nanomedicine [1]. Luminescent nanoprobes (quantum dots, dyes, fluorescent polymers, rare-earth doped nanoparticles, etc) have ever since competed to ensure the best thermal sensitivity in the 20 to 50°C temperature range, as well as high biocompatibility and appropriate size (below 100 nm) for in vivo applications. Due to their high chemical stability and intrinsic luminescence in the near infrared (NIR) region, overlapping with the biological optical transparency window, rare-earth doped oxide nanoparticles (NPs) are promising candidates for in vivo nanothermometry [2].
In this work, Nd³⁺-doped Gd₃Sc₂Al₃O₁₂ (GSAG:Nd) NPs are investigated as luminescent nanothermometers. The development of a new solvothermal synthesis method, combining high temperature (400°C) with high external pressure (200 bar), allows for the elaboration of luminescent GSAG:Nd NPs with an average size of 80 nm [3,4]. The liquid-based solvothermal reaction induces the adsorption of hydroxyl and alcoholic molecules onto the NP surface, leading to the stabilisation of GSAG:Nd NPs in water. Typical Nd³⁺ emission was observed under a 808-nm excitation, with two emission bands centred at 938 and 945 nm, corresponding to the electronic ⁴F_3/2 -> ⁴I_9/2 transition split by the crystal field effect. Thermal sensing properties of Nd³⁺-doped GSAG NPs were found to be excellent for contactless NIR temperature measurements with even higher relative thermal sensitivity as compared to the conventional Nd³⁺-doped Y₃Al₅O₁₂ (YAG:Nd) NPs [5]. Additionally, the presence of Gd³⁺ ions in the GSAG structure offers a further property (MRI contrast), defining GSAG:Nd NPs as multifunctional nanoprobes.

[1] C. D. S. Brites, P. P. Lima, N. J. O. Silva, Angel Millan, V. S. Amaral, F. Palacio, L. D. Carlos, Nanoscale, 2012, 4, 4799
[2] A. Benayas, B. del Rosal, A. Pérez-Delgado, K. Santacruz-Gómez, D. Jaque, G. A. Hirata, F. Vetrone, Adv. Opt. Mater. 2015, 3, 687–694.
[3] G. Dantelle, D. Testemale, E. Homeyer, A. Cantarano, S. Kodjikian, C. Dujardin, J.L. Hazemann, A. Ibanez, RSC Advances 2018, 8, 26857-26870
[4] G. Dantelle, D. Testemale, S. Kodjikian, A. Ibanez, SPIE Proceeding, 2018, 10533, 153322
[5] G. Dantelle, M. Matulionyte, M. Wang, D. Testemale, A. Ibanez, F. Vetrone, in preparation

The aim of this work is the synthesis, optimization and functionalization of organic@inorganic core-shell nanoparticles (NPs), which constitute a novel class of tracers, to be used for deep tissue imaging through two-photon fluorescence microscopy of tumor vascularization. These core-shell NPs, which comprise an organic dye nanocrystal core (ca 40-50 nm) surrounded by a silicate shell, are synthesized using an original ‘spray-drying’ method: atomization of the initial sol-gel solutions followed by the drying of the resulting spray in a horizontal furnace, at 150-200°C, under laminar inert gas flow [1]. This one-step synthesis is made possible thanks to the control of both the sol-gel chemistry (hydrolysis and polycondensation of silicon alkoxides used as shell precursors) and the confined nucleation and growth of the organic core, which occur simultaneously, by tuning the physical parameters of the spray-drying reactor: temperature of the furnace and electrostatic filter, gas flow and atomization parameters. Alkoxide precursors, TMOS (tetramethoxysilane) and TMSE (1.2-bis(trimethoxysilyl)ethane) were particularly selected to form the organosilicate shell. Additionally, an organosilane, (3-azidopropyl) triethoxysilane (AzPTES), is used to impart an azide functionality to the NPs for further functionalization with alkyne-modified moieties using the Cu(I)-catalyzed 1,3-dipolar cycloaddition of organic azides to alkynes (CuAAC). The organic dyes for the nanocrystalline core are non-commercial and designed to exhibit high fluorescence intensity in the crystal-state under two-photon excitation in the red and near infrared (biological window) and the appropriate physico-chemical properties to enable their nanocrystallization [2]. The obtained core-shell NPs feature a very high organic loading (around 30-40%wt). These very high dye concentration is an important advantage of these core-shell NPs to impart strong brightness by enhancing absorption and emission cross sections through the high number of fluorescent molecules. Thus, NPs suspensions showed intense fluorescence emissions around 600 nm. The NPs were then functionalized with different forms of alkyne-modified polyethylene glycol (PEG), differing in chain length and structure using CuAAC to render them furtive and increase their circulation time in the bloodstream of mices [3]. The effects of the NP functionalization and colloidal stability were studied using different characterization tools such as IR and fluorescence spectroscopies, dynamic light scattering and zeta potential under physiological conditions. First in vivo tests of two-photon fluorescence imaging in mice showed bright emissions of these new fluorescent tracers with good circulation time higher than 20 min, while fluorescence was still faintly visible in the blood flow even after a day. These preliminary results are promising for vascular and deep-tissue imaging, particularly for angiography to study for example angiogenesis mecanims in cancer tumors and associated therapeutic treatments.

References
[1.] C. Philippot, F. Dubois, M. Maurin, B. Boury, A. Prat, and A. Ibanez, J. Mater. Chem. (2012),22, 11370
[2] S. Shenoi-Perdoor,, X Cattoën, Y. Bretonnière, G. Eucat, C. Andraud, B. Gennaro, S. Kodjikian, F. Dubois and A. Ibanez. New J. Chem., (2018),42, 15353-15360.
[3] M. Benezra, O. Penate-Medina, P. B. Zanzonico, D. Schaer, H. Ow, A. Burns, E. DeStanchina, V. Longo, E. Herz, S. Iyer, J. Wolchok, S. M. Larson, U. Wiesner, and M. S. Bradbury, J. Clin. Invest. 121(7) (2011) 2768.

Laser particles with sizes of optical wavelengths that are injectable and implantable into biological systems are new, promising light sources and probes for biomedical applications. We present biocompatible semiconductor micro-laser particles for tagging and tracking many cells.

Both theoretical and experimental studies of photoemission spectra of ZnO microspheres and examine the Purcell effect on spontaneous and stimulated emission related to whispering gallery modes are presented. A Mie-basis Green function method, which incorporates contributions from leaky modes, spontaneous as well as stimulated emission processes, and Purcell effect is presented. We show that the spontaneous emission spectrum calculated according to Mie theory (without the Purcell effect) is related only to the contribution of leaky modes, while the spontaneous and stimulated emission both enhanced by the Purcell effect are responsible for the main WGM resonance peaks observed experimentally. It is found that the stimulated emission peaks are doubly enhanced by their respective mode quality factor Q: one factor from the Purcell effect and the other factor from the photon density derived from the rate equation. After taking into account this double enhancement in stimulated emission, the Purcell effect on spontaneous emission, and the leaky-mode contributions, the theory can provide a quantitative description of the detailed fine features of both TE and TM modes observed in the photoluminescence spectra in the whole visible region of ZnO microspheres with various degrees of porosity. The quantitative understanding of the interplay of these emission mechanisms should prove useful for optimizing the performance of light-emitting devices based on micro resonators.

Ultrasound technique arouses great interests in biomedical and clinical application since it holds promise in noninvasive therapeutic studies. Thus, the ultrasound-cell biointerface for drug delivery, neuron stimulation and gene transfection attracted great attention. However, the insufficient resolution and the large device size of current ultrasound technology limit its applications. In this work, we developed a miniaturized optical fiber-based photoacoustic convertor. The convertor is with a diameter of ~500 microns to 1 millimeter and composed of nanoparticle-polymer material to produce localized acoustic wave with controllable frequency in a biomedical relevant range of 0.2-1.9MHz. A coating scheme with a diffusion layer and expansion layer was designed on the tip of the fiber converter. The inverse proportionality between the diffusion layer thickness and the peak frequency was observed. Meanwhile, the light penetration depth of the absorption/thermal expansion layer also exhibited similar inverse proportionality to the peak frequency, offering two approaches toward controllable frequency. Moreover, the acoustic frequency spectrum shows narrow bandwidth (Full width at half maximum FWHM ＜2.5MHz), high angular stability as well as a longitudinal penetration depth of 12 cm in chicken breast,enabling a level of precise control for biomedical ultrasound application. Importantly we demonstrated localized neuron stimulation in vitro and in vivo utilizing the optical photoacoustic convertor. Based on these results, the new miniaturized fiber optoacoustic converter exhibits capability for in-depth study about the biointerface between localized acoustic with tunable frequency and specific cells, benefitting further research and clinical study for imaging, molecule delivery and other therapeutic applications.

Silk fibroin is an abundant natural polymer, which in the last years has been studied as an attractive high-technology material platform, offering new opportunities for photonics and optoelectronics applications. In the field of photonics, silk fibroin-based films have been identified as an interesting optical material due to its transparency from the visible to the near infrared, favoring the development of several devices, such as photonic crystals, diffraction gratings and waveguides. Concomitantly, femtosecond laser direct writing (fs-DLW) has proven to be an important method for materials processing, enabling the fabrication of optical devices in a wide variety of materials, being useful for the obtainment of optical waveguides, microfluidic channels, and 3D flexible electronic circuits. One of the main advantages of fs-DLW is the reduction of thermal effects, which is of foremost importance for processing biomaterials. In spite of that, the usage of femtosecond laser to produce optical elements in silk fibroin has not been demonstrated yet. Therefore, in this work we demonstrate the ability to write optical waveguides in silk fibroin using fs-DLW. Homogeneous, 10-mm long waveguides were fabricated by irradiating a 42-µm thick silk fibroin film with femtosecond pulses, employing a pulse energy of 26 nJ and a scan speed of 100 µm/s. The guiding profile was simulated using the finite element method and experimentally observed by coupling light at 632.8 nm. Such waveguides, having the property of being biocompatible, are promising to be used in the frontier of biophotonics, from implantable medical devices to biosensors.

Integrated photonics, which involves a multitude of miniaturized optical components connected by an optical waveguide network on one single substrate, has thrived over the past decades and is now widely regarded as a transformative paradigm shift in optics and photonics analogous to integrated circuits revolutionizing the electronic industry. Integrated photonics platforms demonstrated thus far are pre-dominantly fabricated on rigid substrates. By imparting mechanical flexibility to integrated photonic structures, the technology bodes significant application potential for imaging, sensing, communications, and consumer electronics. Over the past few years, we have developed a suite of active and passive photonic devices and systems integrated on plastic substrates which can be repeatedly bent, twisted, and stretched without damage. This is accomplished through coherent optical/mechanical co-design, which ensures superior mechanical flexibility and ruggedness of the devices while maintaining, and in some cases enhancing their optical performances. In this talk, the design rationale, fabrication protocols as well as strain-optical coupling behavior in these devices will be reviewed, and their applications in biomedical monitoring and high-speed data communications will be discussed.

Plasmonic nanostructured surfaces have received great attention over recent years. The unique optical properties of plasmonic nanostructures enable chemical and biological sensing using refractive index sensing and Surface-enhanced Raman scattering (SERS). However, there are few reports about the combination of optical biochemical sensing and electrical neural recording. Here, we present plasmonic nanostructure modified multifunctional fiber probes that allow for optical biosensing and neural recording. These fibers are fabricated by thermal drawing process and nanostructured surface modification. We demonstrate the usefulness of this device as a sensitive refractive index sensor as well as SERS substrate. Also, neural recording in wild-type mice confirms that our probes can be used for electrical interrogation of neural circuits in vivo. Technology developed here can be potentially used for in situ in vivo optical biochemical sensing and electrical neural recording.

Neuromodulation has been an invaluable approach for treating neurological diseases. Optogenetics has been developed as a powerful method that is capable of modulating neural activity in rodents. However, application of optogenetics in humans is limited due to its requirement of viral infection. Recently, nanostructures showed great promise for modulating neuronal activities through a minimally invasive manner. Yet, the local temperature rise induced by the thermal effects of nanostructures imposes a fundamental challenge for neuromodulation under physiological condition. To address these challenges, we developed an optoacoustic neuro-stimulation platform via semiconducting polymer nanotransducers (SPN) that efficiently convert pulsed laser energy into acoustic waves to enable highly localized stimulation of a neural tissue. Here, we demonstrated that the designed SPNs can strongly absorb light in the near-infrared second window (NIR-II, 1030nm), enabling enhanced light penetration depth through the skull. We further bioconjugated the surface of SPNs with antibodies targeting mechano-sensitive channels, TRPV4, to specifically bind to the neural membrane within 1 hour. By locally perturbing the mechano-sensitive channel, SPN can trigger repeatable action potential firing of embryonic cortical neurons with a laser duration of 3 ms. With enhanced temporal and subcellular spatial resolution, the as-designed SPNs showed potential in precise control of the neuronal circuits in the brain for basic neuroscience studies and treatment of neurological disorder diseases.

We report here monocrystalline silicon nanomembrane based optical waveguides, photonic crystals, and Fabry-Perot cavities for bioresorbable sensors. Both micro- and nano-scale structures have been designed, fabricated, and characterized for gas, liquid, pressure, temprature, and other physicalogical parameter monitoring.

Development of safe and efficacious neural interfaces is important for the treatment of a broad range of neural diseases such as Alzheimer’s disease, restoration of motor activity, and blindness due to retinal degeneration [1]. Two basic charge transfer mechanisms, Faradaic and capacitive processes, have been widely used for neural interfaces [2,3]. Faradaic charge transfer involves the charge carrier injection in the extracellular medium with chemical reactions, which may generate harmful side products. Alternatively, capacitive charge transfer is originated by the movement of ions via electromagnetic interactions without any reaction. For neural photostimulation, semiconducting polymers have engrossed significant attention due to their easy solution processability, biocompatibility, flexibility and conformability [4], and capacitive photostimulation by organic interfaces offers a safe and long-term neural stimulation strategy.
Here, we demonstrate a photoelectrode architecture that can generate capacitive photostimulation. We use a bulk heterojunction of P3HT(Poly(3-hexylthiophene-2,5-diyl):PCBM[(6,6]-phenyl-C61-butyric acid methyl ester) for the photoactive layer, which is biocompatible and can stimulate neurons [4, 5]. We explore the photoactive layer on zinc oxide nanoparticles, which is deposited on ITO layer. The photocurrent measurements suggest that the photoelectrode shows capacitive charge transfer mechanism. Further, electrophysiology experiment using patch pipette in voltage clamp mode is performed on ShSy-5Y neuronal cells and strong depolarization is observed by 10 ms light pulses in the visible range. Moreover, the results are confirmed by theoretical two-domain-stimulation model as well. In perspective, utilization of metal oxide for controlling photostimulation mechanism provides a new opportunity for safe and extended photostimulation of neurons.

References
1. O'Brien, E.E., et al., Electronic restoration of vision in those with photoreceptor degenerations. Clinical and Experimental Optometry, 2012. 95(5): p. 473-483.
2. Cogan, S. F. Neural stimulation and recording electrodes. Annu. Rev. Biomed. Eng. 10, 275-309 (2008).
3. Jalali, H. B., et al., Effective neural photostimulation using Indium-based type-II quantum dots. ACS Nano, 2018. 12(8): p. 8104-8114.
4. Ghezzi, D., et al., A polymer optoelectronic interface restores light sensitivity in blind rat retinas. Nat Photonics, 2013. 7(5): p. 400-406.
5. Ghezzi, D., et al., A hybrid bioorganic interface for neuronal photoactivation. Nature Communications, 2011. 2: p. 166.

In this paper, we demonstrate the stain-resistance and high-pressure stability of superomniphobic flexible optical plastics. A scalable method for creating nano-enoki mushrooms in plastics is presented that provides for the re-entrant geometry needed to prevent inltration from a variety of liquids. The surface demonstrates static contact angles over 150° and low contact angle hysteresis under 20° for a wide variety of organic liquids. The re-entrant tops and fluorination of the nano-enoki, as well as the few micron spacing between nanostructures, provide for robust metastable solid-liquid-air interfaces in the presence of Laplace pressures of at least 900 Pa. In addition, compared to the initial bare plastic, the nano-enokis demonstrate comparable transmission values (86.4% versus 88.4% at a wavelength of 550 nm) and ultrahigh haze values (96.4% versus 1.1%). The surfaces exhibit stain-resistance for a variety of liquids including mustard and blood, where dried blood and mustard both flake off the samples without any residue. We also performed durability experiments which demonstrate that nano-enoki
plastics are robust from bending with similar transmission, haze, wetting contact angle and hysteresis values after 5000 cycles of bending.

In recent years, there has been a tremendous advancement in bio-inspired electronic devices. Multiscale structures of biological materials exhibit inherent multifunctional integration. Special properties of biological materials provide motivation to scientists and engineers to design highly efficient electronic devices. Inspired by this, we used a protein photosystem I to make efficient photoelectrochemical cells. Photosystem I (PSI, ∼500 kDa protein super complex) has been widely used to efficiently capture sunlight, which can create efficient biohybrid photoenergy conversion devices. During photosynthesis, photoexcited electrons are transported at a 1 μs time scale across the thylakoid membrane by using PSI as a photodiode at a quantum efficiency closing to 100%.
Since PS I (photosystem I) protein has light induced property, it can be utilized to convert solar energy to electrical energy in Photoelectrical cells. We used this light inducing property of PS I and made biohybrid photoelectrochemical cell using gold surface. Biohybrid photoelectrochemical cell provides novel results on the relationship between surface plasmon generation (SPG) efficiency of nanoslits and the experimentally obtained photocurrent generation, by immobilizing PS I on gold nanoslit electrode surfaces.
Semi-analytical model was used to calculate SPG (Surface Plasmon Generation) efficiency for varying nanoslits (50 nm, 100 nm, 200 nm, 300 nm or 400 nm). FDTD (finite difference time domain) simulation was also done to find which nanoslits have maximum electromagnetic field enhancement around their surface. Different Nanoslits (50nm, 100 nm, 200 nm, 300 nm or 400 nm) were fabricated with the help of photolithography technique and FIB (focused ion beam). After that, the PS I protein was immobilized on the Nanoslits with the help of self-assembly monolayer formation, and photocurrent generation for each nanoslit was measured using electrochemistry setup. The results show the relationship between SPG efficiency of nanoslits and experimentally obtained photocurrent, by immobilized PS I on the gold nanoslit electrode surface. The photocurrent generation (G) and SPG efficiency for the nanoslit electrochemical devices (D) is a function of nanoslit width. The energy conversion (photocurrent) is greatly enhanced, which is correlated to the SPG efficiency and EM field enhancement in the nanoslit. This finding can be attributed to the phenomenon of plasmon-exciton coupling effect on the PSI in the nanoslits. The enhanced photocurrent generation was explained on the basis of plasmonic light trapping and plasmon-induced resonance energy transfer.

Optical and photonic properties of porous anodic alumina (PAA) layers have gained considerable attention of late.[1] Although pure alumina is known to be a reflective, transparent and intrinsically colorless insulating material, the absorption of light of certain wavelengths can be achieved in PAA due to photonic effects and destructive interference.[2] It is known from previous studies that there is a correlation between such parameters as the pore size and inter-pore distance and the nominal wavelength of the maximal destructive interference, and consequently also observable optical characteristics. Therefore, PAA with different introduced degree of disorder should demonstrate the absorption in a larger wavelengths interval. Black coloring of PAA films is frequently observed when the phenomenon called “burning” (that is a strong increase of the electrical current, accompanied by local etching and distortion of the ordered structure) occurs during the electrochemical synthesis.[3] However, the nature of this coloring remains relatively unexplored.
Here, we demonstrate that the black coloration mechanism in PAA is identical to the one that already exists in natural structurally colored surfaces, or in some artificially created biomimetic structures (similar to the ‘moth eye effect’ or the coloration of the pied paddy skimmer dragonfly wings surface). According to our measurements, the chemical composition of the PAA films has only a minor influence on the coloring and the increase of the optical density, and that the light absorbing properties mostly likely result from the structural effects. Blackened PAA layers synthesized in our work exhibit strong adhesion to Al surface, are cost-effective and suitable for application under harsh conditions such as elevated temperatures or irradiation by UV-light. Thus, they are potentially useful for many areas including construction of optical devices and aerospace technologies. For instance, they can find application as resistant coating for heat elimination which is compatible with lightweight and durable Al-based alloys.

1. Santos, A., Nanoporous Anodic Alumina Photonic Crystals: Fundamentals, Developments and Perspectives. J Mater Chem C 2017, 5, 5581-5599.
2. Pashchanka, M.; Yadav, S.; Cottre, T.; Schneider, J. J., Porous Alumina-Metallic Pt/Pd, Cr or Al Layered Nanocoatings with Fully Controlled Variable Interference Colors. Nanoscale 2014, 6, 12877-12883.
3. Ono, S.; Saito, M.; Asoh, H., Self-Ordering of Anodic Porous Alumina Induced by Local Current Concentration: Burning. Electrochem Solid St 2004, 7, B21-B24.

Electronic devices have been widely used by modern people for everyday life and industry. To achieve both portability and performance goals, devices have become increasingly smaller and more highly integrated, making them more susceptible to interference from electromagnetic waves. To prevent this, there is an increasing demand for an electromagnetic shielding film which is light, thin, reflects little and absorbs a lot. Such a shielding film also reduces the influence of electromagnetic waves on the human body. As a candidate for a thin and light electromagnetic shielding film, a film containing a magnetic material of a ferrite type has been mainly considered. Particle size and nanostructure of magnetic materials at nanoscale have been optimized to absorb the electromagnetic wave. In case of the nanofiber which has one-dimensional structure, the electrical conductivity increases and it will be positively affected to absorb an electromagnetic wave. We have fabricated the composite nanofibers including iron, nickel and zinc nitrate using electrospinning method which can easily make a uniform fiber structure. The composite nanofibers were heat-treated to volatilize and crystallize to obtain Ni_0.5Zn_0.5Fe₂O₄ spinel ferrite phase, and its microstructure, crystal phase, and magnetic hysteresis loop were analyzed. The spinel ferrite phase and average diameter of ~ 200 nm in Ni_0.5Zn_0.5Fe₂O₄ nanofibers were confirmed by X-ray diffraction and field-emission scanning electron microscope, respectively. The magnetic properties of Ni_0.5Zn_0.5Fe₂O₄ nanofibers with average diameter were observed through the vibrating sample magnetometer. The film to absorb an electromagnetic wave was fabricated using the Ni_0.5Zn_0.5Fe₂O₄ nanofibers as a filler. The absorbing properties of ~11 dB at 10 GHz were measured by a vector network analyzer. The microstructure of the Ni_0.5Zn_0.5Fe₂O₄ nanofibers was optimized and suggested to apply to electromagnetic wave shielding.

Silicon nanoparticles have large absorption coefficients compared to the bulk while also being highly emissive with reported photoluminescent quantum yields as high as 50%. These nanoparticles would be of great interest as sensitizers for triplet fusion based photon upconversion to convert low energy light from the NIR window I into the visible spectrum. Photosensitized triplet excitons can be harvested from the nanoparticle by grafting organic transmitter ligands to the surface of the Si nanoparticle. These bound transmitter ligands will mediate energy transfer from the nanoparticle, and ultimately to a free molecular emitter. The emission wavelengths from this upconversion platform will be highly tunable by altering the levels of conjugation in the organic ligands i.e. perylene to anthracene to tetracene. These silicon nanoparticle systems would be useful for light sensitized biological disciplines as it is biologically benign and the NIR excitation light is physiologically transparent allowing for high penetration depths.

We studied GaAs:Mg doped nanostructures grown by MBE on GaAs (001) oriented substrate. A pyramidal structure (~3-10 Microns) has been obtained for several deposition conditions and varying the temperature it has been observed a change on the density of these pyramids. Complementary to direct optical imaging by microscope, Confocal Raman Spectroscopy which is widely applied to study nanostructures, has been used to determine the different phonon modes presented. In order to study the pyramidal structures, Confocal Raman Spectroscopy analysis of the surface allows profiling the Raman intensity of the different phonon modes over a scan area. Raman spectroscopy allows not only structural parameters such as superlattice periodicity and layer composition to be determined, but also by scanning it provides information of the pyramidal structures size, shape and strain. Moreover, we have been able to scan an area with depth profiles giving as a result a stack used to obtain 3D (tomographic) spatial information of the sample. Therefore we were able to determine the composition and strain of the pyramids via 3D imaging compared to the flat film area. Although, it has been observed by Raman Spectroscopy that the GaAs TO signal is downshifted due to the Mg doping which is more intense within the pyramid area, indicating that the micrometric structures are mainly related to the incorporation of Mg to the GaAs. The confocal area image was color pattern for the different phonon modes to be able to study the growth of the pyramidal structure and relate it to the deposition temperature.

On-chip fabricated rolled-up microtubes act as ultra-compact components in fully integrative lab-in-a tube systems for single cell analysis [1]. These microtubes are equipped with photonic functionalities to generate new types of optofluidic and opto-plasmonic components for novel sensing and detection schemes in 3D microtubular optical cavities [2,3]. Microtubes also sit at the core of microrobots, which in the ultimate limit should perform relevant biomedical tasks in the human body. However, tracking and imaging medical microrobots in deep tissue represent a major challenge in this field [4]. A decisive step in tackling this challenge will be presented in the talk.

[1] S.M. Weiz, M. Medina-Sánchez, O.G. Schmidt, Adv. Biosystems 2, 1700193 (2018)
[2] Y. Yin, J. Wang, X. Lu, Q. Hao, E. Saei Ghareh Naz, C. Cheng, L. Ma, O.G. Schmidt, ACS Nano 12, 3726 (2018)
[3] J. Wang, Y. Yin, Q. Hao, Y.D. Yang, S. Valligatla, E. Saei Ghareh Naz, Y. Li, C.N. Saggau, L. Ma, O.G. Schmidt, Nano Lett., DOI: 10.1021/acs.nanolett.8b03453
[4] M. Medina-Sánchez, O.G. Schmidt, Nature 545, 406 (2017)

Advances in large-area organic electronics for electronic skins and biointerfaces demand highly stretchable, patternable and conformal electrodes to minimize contact resistance when sensing devices are mechanically deformed. Gold is an excellent electrode material with work function matching well with p-type organic transistors. However, it is non-trivial to fabricate highly stretchable gold electrodes for stretchable organic electronics. Here by combining the advantages of both top-down patterning and bottom-up synthesis, we introduce a new materials platform of patterned vertically-grown gold nanowires (AuNWs) for constructing intrinsically stretchable electrodes, with high conductivity of 1,288 S/cm at 0% and 152 S/cm at 170% strain. Such patterned vertical AuNWs can be embedded in elastomer matrix, leading to stretchable electrodes that are mechanically robust and durable. The interface between AuNWs electrodes and poly(3-hexylthiophene) (P3HT) thin film shows ohmic contact for the entire strain regime from 0% to 100%, indicating low contact resistance. We further demonstrate a stretchable organic transistor with ion gel as dielectric, which can survive up to 100% without much performance degradation. The results presented here indicate that our methodology may be extended to other organic semiconducting materials and devices, hence, offering a general electrode materials platform for devising high performance intrinsically stretchable organic electronics.

In order to understand the functional network in the brain and to treat brain-related disorders effectively, it is of great importance to discover the relationship between different brain regions, and many technologies have been developed based on that need. The widely adopted neural interfacing devices are metal-based microwires and silicon-based multichannel arrays, which have excellent recording capability with high signal to noise ratio. However, the mechanical property mismatch between these rigid devices and soft brain tissue can lead to neuron death and device failure in long term implant. Recently, polymer fiber-based neural probes have shown advantages over conventional neural interfaces in terms of flexibility and biocompatibility. However, so far the functions of fiber-based probes have been restricted to the tip area, significantly limiting the application of these devices. Here we present the femto-second laser micromachining on the longitudinal surface of the multifunctional polymer fiber, which can expose multisite electrodes, microfluidic channels, and waveguides along the fiber length. Using this micromachining technique, we can pattern the fiber surface with arbitrary geometry and spacing on the fiber longitudinal surface with a submicron resolution. Therefore, we can investigate different brain regions’ responses toward stimulation at different locations, and have a better understanding of the signal correlation in between. In this study, we performed simultaneous optical stimulation and multisite electrical recording in transgenic mouse brain using a single fiber probe, and analyzed the correlation between the signals recorded from different brain regions. We also patterned microfluidic channels and delivered fluorescence dyes into multiple locations in the brain, which can be used for multisite drug delivery in the brain. Furthermore, chronic recording and long term tissue responses were examined to evaluate our multifunctional neural probes as chronic neural interface devices. The femto-second laser micromachining significantly expands the capability of multifunctional fiber-based neural interfaces, which can lead to wide applications in neuroscience.

Since the advent of optical microscopy, a flat glass microscope slide has been the standard surface upon which tissues, cells, and biomolecules are attached for observation. Recently, we have utilized the optically resonant properties of nanostructured photonic crystal (PC) surfaces to enable several new microscopy modalities where the nanostructure provides new forms of contrast for a wide variety of compelling applications. By designing PC surfaces with resonances that match the excitation and emission spectra of photon emitters such as fluorophores and quantum dots, PC enhanced fluorescence (PCEF) microscopy reduces the detection limits of any surface-based fluorescence assay. By generating spatial images of the PC resonant reflection intensity, we can selectively and dynamically visualize the cell-extracellular matrix interface during processes that include stem cell differentiation, cancer cell response to drugs, and chemotaxis – including the ability to observe the formation and evolution of cell membrane focal adhesion sites. We call this approach Photonic Resonator Outcoupler Microscopy (PROM), as we observe highly localized outcoupling of light from the PC that occurs due to scattering by dense regions in the cell membrane. Further, by utilizing metallic nanoparticle tags with plasmon resonances that match the PC resonance, we obtain highly efficient coupling of light into nanometer-scale electromagnetic hotspots, that is accompanied by highly localized “quenching” of the PC reflection efficiency, which we are using for digital-resolution detection of miRNA biomarkers for cancer with 100 aM limits of detection, using an approach called Photonic Resonator Absorption Microscopy (PRAM). The seminar will describe the physical principles, nanostructure design/fabrication, instrumentation, and applications for nanostructure-enabled microscopy for disease diagnostics, personalized medicine, and life science research.

Engineered silicon-based materials display photoelectric and photothermal responses when illuminated by light, which allows for innovation at silicon-biology interfaces. Silicon nanowires have small radial dimensions, which are promising for use as highly localized cellular modulators. However, the single crystalline form's photothermal efficacy is limited due to the poor light absorption and fast heat dissipation. In this presentation, we will discuss (1) the strategies to improve the photothermal response from silicon nanowires by introducing nanoscale textures on the surface, and (2) the high-resolution extracellular modulation of calcium dynamics in a number of mammalian cells using these improved materials. To produce the textured silicon nanowires, I will highlight an alloy-assisted deposition to form three-dimensional arrays of atomic gold catalyst on the silicon surface.^[1] These single atoms catalyze the chemical etching of silicon, producing ordered 3D grooves over the entire nanowire surface. This newly designed silicon-cell interface may be broadly used in probing and modulating electrical and chemical signals at the sub-cellular scale^[2,3], a currently challenging topic in the field of electrophysiology and cellular engineering.


References:
[1] Fang, Y., Jiang, Y. W., Tian, B. Z., et al., Alloy-assisted deposition of three-dimensional arrays of atomic gold catalyst for crystal growth studies, Nat. Commun. 8 (2017), 2014
[2] Fang, Y., Tian, B. Z., et al., Texturing silicon nanowires for highly localized optical modulation of cellular dynamics, Nano Lett. 18 (2018), 4487
[3] Jiang, Y. W., Tian, B. Z., et al., Rational design of silicon structures for optically controlled multiscale biointerfaces, Nat. Biomed. Eng. 2 (2018), 508

The accurate monitoring of cell electrical activity is of fundamental importance for pharmaceutical research and pre-clinical trials that impose to check the cardiotoxicity of all new drugs. Such a strong interest stimulated the development of methods for intracellular recording of action potentials on a large scale. Currently, the most promising results are represented by multi-electrode arrays (MEA) refined with 3D nanostructures that were introduced in pioneering seminal papers^1,2, culminating with the recent work from the group of H. Park³, where they show intracellular recordings on high-density CMOS-based MEA refined with 3D nanopillars. However, the requirement of 3D nanostructures limits the practical exploitation of these techniques. First, the fabrication of 3D nanopillars is an extremely complex and expensive procedure, hardly applicable to large area production. Second, cells’ interaction with 3D nanopillars is still under investigation^4,5, with unresolved questions about their interaction, especially in case of mechanically contracting cardiomyocytes. Finally, most of the works exploited electroporation, which complicates considerably the circuit design of high-density CMOS circuits. Thus, despite pioneering results have been obtained on both passive and active MEAs, these technologies have not yet been applied to practical cases nor reached the commercial phase.
Here, we introduce the concept of planar meta-electrodes and we show for the first time that high quality intracellular signals can be recorded on high-density commercial CMOS-MEAs without any rework of the devices, without 3D nanostructures nor circuitry for electroporation⁷. The intracellular recording is obtained by means of laser optoacoustic poration mediated by a meta-electrode, which is a porous platinum electrode with a dual optical/electrical function. Optically, it behaves like a strong broadband absorber in the near-infrared, as it has been recently shown for metasurfaces in general⁸. Electrically, it provides strong cell coupling due to the tight sealing of the cell membrane on the porous morphology. When illuminated with a short laser pulse, the plasmonic response of porous platinum enables the generation of localized high electric field hot-spots that produce shockwaves^9,10 able to open the cell membrane. This enables high quality intracellular recordings with no side effects. We will show sharp intracellular action potentials of human derived cardiomyocytes on a commercial CMOS-MEA. To prove the direct application to pharmacological screening, we will also show the exploitation of our approach to detect the effects of typical drugs and toxins on the cell cultures, thus confirming the high potential of the technique to improve pharmaceutical tests. The technique offers lower development and recurring costs due to the “already commercial” nature of the employed devices. Our work paves the way to a completely new set of affordable and effective methods for studying electrogenic cells. Moreover, the new meta-electrodes may have extreme impact on combining optical and electrical investigations for biochemistry and biology that require today new multifunctional tools¹¹.

References
1- Xie C. et al., Nat. Nanotechnol. 2012, 7, 185–190
2- Robinson J.T. et al., Nat. Nanotechnol. 2012, 7, 180–184
3- Abbott J. et al., Nat. Nanotechnol. 2017, 12, 460–466
4- Capozza R. et al., ACS Appl. Mater. Interfaces 2018, 10 (34), 29107-29114
5- Dipalo M. et al., Nano Lett. 2018, 18 (9), 6100–6105
6- Spira M.E. et al., Nat. Nanotechnol. 2013, 8, 83–94
7- Dipalo M. et al., Nat. Nanotechnol. 2018 13 (10), 965-971
8- Meinzer N. et al., Nat. Photonics 2014, 8 (12), 889–898
9- Zilio P. et al., Light Sci. Appl. 2017, 6, e17002 (2017)
10- Dipalo M. et al., Nano Lett. 2017, 17 (6), 3932–3939
11- Caprettini V. et al., Adv. Sci. 2018, 5 (12), 1800560

Stretchable electronics has expanded the application scope of the electronics and sensors particularly for health monitors, medical implants, artificial skins and human-machine interfaces. To accommodate the mechanical stretchability to nonstretchable electronic materials, the structural engineering design from special mechanical structures or architectures has been widely exploited. An alternative route to eliminating the burden of constructing dedicated architectures and the associated sophisticated fabrication processes is to build stretchable electronics from rubbery electronic materials, which have potential toward scalable manufacturing, high-density device integration, and large-strain tolerance.

Here, I would like to present our recent progress on developing fully rubbery electronics from intrinsically stretchable rubbery composite materials of semiconductors and conductors, which can be scalably manufactured from common and commercial available materials without dedicated and complicated synthesis. Specifically, we build nanofibril organic semiconductor and metallic nanowires percolated in the elastomeric polymer matrix in a composite format for the rubbery semiconductors and conductors, respectively. Employing these rubbery electronic materials, we have achieved fully rubber format devices, including transistors and sensors, logic gates, active matrices, and elastic sensory skin systems etc. The rubbery stretchable electronics holds a wide range of applications, such as artificial skins, biomedical implants, and wearable applications.

With the emergence of the internet of things (IoT) era, visual IoT platforms have attracted significant interest, which can offer sensing, collecting, and processing of optical information in hyperconnected society. Flexible displays are a potential candidate for bilateral visual communication, as they can be easily affixed anywhere, such as on the surfaces of human skin, clothes, automobiles and buildings. III-V Inorganic LEDs have superior characteristics, such as long-term stability, high efficiency, and strong brightness compared to OLED. However, due to the brittle property of inorganic materials, III-V LED limits its applications for the flexible electronics. This seminar introduces the flexible vertical GaAs/GaN microLED on plastic substrates using anisotropic conductive film (ACF), resulting high optical power density, The superb properties of the flexible inorganic LED enable the dramatic extension of flexible displays toward not only wearable devices of light source but also full color flexible micoLED displays for consumer TV.
MicroLED stimulation of specific neural populations of the brain is one of the facile and reliable methods used in neuroscience for deduction of functional movement, complex behavior and even long-range connectivity. Recent advanced biomedical tools now employ flexible optoelectronic devices combined with optogenetic mouse models to activate small functional regions using blue-light driven channelrhodopsin. Here we introduce flexible vertical light-emitting diodes (VLEDs) for 2D perturbation of specific functional areas of mouse cortex, capable of stimulating motor neurons deep below layer III from the brain surface. Selective operation of pulsed red light from f-VLEDs induces mouse body movements and synchronized electromyogram (EMG) signals. These results show that the III-V based flexible LED can be used as the future flexible implantable biomedical applications such as skin research and phototherapeutic tool.

References of Keon’s corresponding authors since 2014
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[9] Adv. Mater. 28, 8371, 2016, [10] Adv. Mater, 26, 2514, 2014, [11] Adv. Mater., 29, 1603473, 2017, [12] Adv. Mater, 29, 1606586, 2017
[13] Adv. Mater, 27, 1701138, 2017, [14] Adv. Mater, 29, 1700595, 2017, [15] Nano Letters 14, 7031, 2014, [16] Energy Environ. Sci. 8, 2677, 2015, [17] Energy Environ. Sci., 7, 4035, 2014, [18] Adv. Energy Mater. 6, 1600237, 2016, [19] Adv. Energy Mater. 5, 1500051, 2015, [20] ACS Nano 9, 4120, 2015, [21] ACS Nano, 10, 3435, 2016, [22] ACS Nano 8, 9492, 2014, [23] ACS Nano 8, 7671, 2014, [24] ACS Nano, 9, 6587, 2015, [25] ACS Nano, 10, 10851, 2016, [26] ACS Nano, 10, 9478, 2016, [27] ACS Nano, 12, 9587, 2018, [28] Adv. Func. Mater. 24, 6914, 2014, [29] Adv. Func. Mater. 26, 6170, 2016, [30] Adv. Func. Mater. 27, 1700341, 2017, [31] Adv. Func. Mater. 28, 1801690, 2018, [32] Adv. Func. Mater. 24, 2620, 2014, [33] Nano Energy, 35, 415, 2017, [34] Nano Energy, 14, 111, 2015, [35] Nano Energy, 44, 447, 2018, [36] Nano Energy 53, 198, 2018, [37] Nano Energy, 53, 658, 2018, [38] Adv. Sci., 1801146, 2018

Substantial progress has been made in development of graphene-based transparent optical interfaces enabling concurrent integration of electrophysiological recordings, optical imaging and optogenetics. However, the impedance of transparent graphene electrodes is relatively high, limiting its scalability and its use for microstimulation. As a result, high impedance of graphene constitutes a big challenge toward the widespread use of transparent electrodes. Here, we experimentally investigate the origins of high impedance in graphene microelectrodes and demonstrate that the impedance of graphene microelectrodes is fundamentally limited by quantum capacitance. We overcome this quantum capacitance limit by creating a parallel conduction path using electrochemically deposited platinum nanoparticles. This approach achieves a 100 times reduction in graphene electrode impedance, while maintaining the high optical transparency crucial for deep two–photon microscopy. Using a transgenic mouse model, we demonstrate simultaneous electrical recording of cortical activity with high fidelity while imaging calcium signals at various cortical depths right beneath the transparent microelectrodes. Multimodal analysis of Ca²⁺ spikes and cortical surface potentials offers unique opportunities to bridge our understanding of cellular dynamics and brain–scale neural activity.

Incorporation of metallic nanoparticles (NPs) in polymer matrix is well established and has been used to enhance and control dissolution and release of drugs, for targeted drug delivery, antimicrobial agents, localized heat sources, mechano-responsive nanocomposites, and for unique optoelectronic applications. Colloidal gold NPs (Au_c) in particular exhibit a plasmonic response that can be utilized for photothermal applications. Dispersion of Au in polymers creates a hybrid material with increased robustness, responsiveness, and flexibility while intrinsic nanoparticle properties are maintained.
In previous work, colloidal gold (Au_c) NPs were incorporated into electrospun (ES) polyethylene glycol fibers (Au_c/PEG) to utilize the nanoparticle plasmonic response for localized heating of the polymer. Applications of this work were anticipated for localized heating and melting of drug-carrying polymer fibers for light-activated release. Using broad spectrum white light interrogation, the Au_c used exhibited a maximum absorbance at 522 nm on ultra violet visible spectroscopy (UV-Vis) which was the same when Au_c was incorporated into bulk polymer (58 wt% in PEG 8000 MW). Using trapezoidal integration of the energy absorption difference curve, the theoretical energy absorption for Au_c/PEG was calculated to have an efficiency enhancement of 9.6 % under white light illumination and 38.3 % under green light illumination compared to PEG alone.
Maximum absorbance of these materials in fiber form was recorded at 504 nm. Au_c/PEG fibers were ES directly onto resistance temperature detectors (RTDs) so that resistance of the materials could be measured. To maximize the response of the polymer, white light was substituted for green laser light (λ=533 nm), and resistance measured was converted to temperature change using the Callendar-Van Dusen equation. Results showed an increase in temperature of the Au_c/PEG fiber by 9 °C. A drawback to Au_c/PEG electrospun mats was a propensity for electrospraying and droplet formation instead of depositing a fibrous mat that could be peeled up from the deposition surface and distributed as a drug-delivery device. To counter this issue polyethylene oxide (PEO; 200,000 MW) was blended with PEG in various ratios to improve polymer viscosity and resultant material properties for distribution. PEG was blended with PEO at a ratio of 3:2 respectively, creating a “peelable” fiber mat which still responded to green laser light with an increase in temperature of 7 °C.
To further understand the plamonic material properties associated with gold dopants in polymer, Au_c and gold nanorods (GNRs) were incorporated into PEG thin films for characterization. The GNRs used exhibit a tunable longitudinal surface plasmon resonance that depends on the GNR aspect ratio. While Au_c used for this work were bought commercially, GNRs were synthesized with a novel, secondary (seeded) growth procedure which allows improved control over aspect ratio and size of GNRs. Aspect ratio control during synthesis results in GNRs with resonances tuned between 760 and 820 nm in order to vary interactions with λ_808nm activation optical source. Using spectroscopic ellipsometry (J.A. Woollam M-2000 U), the complex optical constants of drop cast films will be determined for calculation of material absorbance. In addition, a camera system will be used to map temperature changes throughout the polymer films. The camera system described is a FLIR A35sc benchtop thermal camera system equipped for sample illumination achieved with a variable power λ_808nm light emitting diode. Electron microscopy will be used to determine fiber mat quality. Coupled with our previous work that measured temperature change of doped polymer mats on RTDs, these results will provide a good foundation for future development of light-activated plasmonic resonance in polymer materials with numerous applications.

Implantable electronic systems are being increasingly utilised to provide therapeutic benefit. Exemplars include pacemakers for the heart and brain, neuromodulators for bladder and pain control, and sensory prosthetics for sound and vision. Traditionally such systems would comprise two primary units: A hermetic case which contains the control electronics, and a lead with electrodes which provide recording or stimulus. Such systems are typically limited to a few dozen electrodes, as such, there is now a strong interest in placing active electronics which can multiplex hundreds/thousands of optical and/or electrical interfaces.
In Newcastle University, we are developing a new type of clinical-grade optoelectronic implant to prevent seizures in patients with focal, drug-resistant epilepsy, and a project called CANDO. We are utilising a gene therapy technique called optogenetics which renders the brain tissue light sensitive. We can then electrically record and optical stimulate at the same time, providing closed loop control of the seizure focus.
The CANDO control unit is similar to others in the domain – i.e. battery and control electronics sitting in a hermetic case with hermetic feedthroughs to cables connecting to a brain unit. However, we have chosen our brain unit to consist of active electronics, to allow for multiplexing of multiple optical stimulation points whilst simultaneously recording. The active electronics is fabricated from a standard complementary metal oxide semiconductor (CMOS) process by a foundry (Austria Microsystems) under a commercial process. The chips have been designed to incorporate a digital communication and control scheme as well as driver electronics for individual light emitting diodes, self-diagnostic circuitry, and amplifiers and analog to digital converters to acquire neural signals. The active electronics connect to penetrating shafts with electrodes and optical microemitters for stimulation and recording.
We have demonstrated efficacy of our optoelectronic probes in the acute setting and with recordings and stimulus on both rodent and non-human primate animal models. We are now beginning long term chronic animal studies to understand the efficacy of different control algorithms for preventing seizures.
For acute research purposes, electronics fabricated from standard complementary metal oxide semiconductor (CMOS) processes, can rely on the silicon oxy-nitride top layer. However, bond wires and bonded surface components such as the photonic microemitters need encapsulation to prevent shorting between anode and cathode contacts by the saline. As such, we encapsulate our system in poly-dimethyl-siloxane.
There are important considerations in the design of encapsulation of such devices:
Insulation and hot spots: Light emitting diodes are typically 5-40% efficient. The rest of the energy provided to them is emitted as heat. However, the regulations state that the surface of implantable devices should not exceed 2^OC. The encapsulation acts as a thermal insulator, so if it is too thin, there can be local hot-spots above the LED. However, if it is too thick, there can be hotspots at neighbouring electrodes.
Failure mechanisms: Implantable devices need to last years, perhaps decades in the brain. We are therefore exploring accelerated lifetime studies of failure modes including optical, thermal-cycling and delamination effects.
Electronic driving: We are exploring how different electronic driving modes of the underlying (opto)electronics can affect the encapsulation integrity. We find this to be highly significant.
These three considerations are part of long-term studies which have already been initiated and will form the basis of our regulatory submission. Evidence on each will be presented with conclusions for the materials community.

Nanostructured materials possess a number of unique properties such as tunable optical and electronic property, high surface-to-volume ratio, mechanical flexibility, etc. These intriguing properties can be harnessed for a variety of applications in flexible electronic and photonic devices. In the past, we have fabricated an assortment of arrayed nanostructures consist of nanowires, nanopillars, nanocones, etc., using a variety of materials from inorganic semiconductors to organic-inorganic hybrid materials. These nanomaterials/nanostructures have been fabricated into a variety of functional devices including solar cells, supercapacitors, light-emitting diodes, gas sensors, etc. By manipulating light and charge interactions with nanostructures, the performance of these devices can be largely tuned. And if the nanostructures are rationally designed, the performance of devices can be significantly improved. Here we will present the fabrication methods of nanostructures and design rules of nanostructures for these high performance electronic and optoelectronic device. And the integration of these devices into concept proof wearable systems will also be demonstrated.

Yttrium vanadate host crystals co-doped with trivalent lanthanides and bismuth have been extensively used for wide-range of applications such as red phosphors in cathode ray tubes (CRTs), near-UV white light emitting diodes (LEDs), spectral down-shifters for solar cells, laser host material, and bioimaging, owing to their high luminescent efficiency upon electron-beam excitation. Biomedical applications are particularly of interest due to high photochemical stability, low toxicity, large (anti-)Stokes shifts, sharp emission spectrum, and reduced photobleaching of lanthanide based luminescent materials. Superior photochemical stability of lanthanide doped YVO₄ can replace conventional organic dyes and quantum dots (QDs) in bioimaging applications and provide low cost alternatives to labor intensive analytical tools such as enzyme-linked immunosorbent assays (ELISA) in sensing applications. In the present study, the effects of separating Bi³⁺ from Eu³⁺ ions were studied via a core-shell nanoarchitecture, with the aim of developing nanomaterial with longer luminescent lifetimes which is sensitive to variations in the electric dipole at the surface. Bi³⁺ doping in the YVO₄ lattice is hypothesized to increase the sensitivity and photo durability of the system, specifically when the Bi³⁺ ions are separately doped in the shell layer, closer to the surface, while the Eu³⁺ ions in the core are shielded by the YVO₄ shell from the surface quenchers. The effects of weak electric dipoles (NH₂⁺-BZA and NO₂^--BZA) on luminescence lifetime and spectroscopic properties of the core and core-shell nanoparticles (NPs) were then investigated to verify the expected advantage of utilizing a doped core-doped shell system over the commonly used co-doped cores. The ability to manipulate the excitation intensity, which gives rise to turning the luminescence emission “on and off”, justifies the need for separating Bi³⁺ from Eu³⁺ ions and moving the Bi³⁺ closer to the surface to systematically amplify the effect of weak electric dipole. Moreover, only a small decrease in luminescence lifetimes of the functionalized core-shell NPs has been observed for both NH₂⁺-BZA and NO₂^--BZA functionalized core-shell NPs; this decrease in lifetime is less prominent for core-shell system compared to core NPs, highlighting another advantage of using core-shell NPs over core NPs. Finally, the surface of the core-shell NPs was modified with D-biotin to ensure comparable sensitivity of the NPs to more biologically relevant molecules, which is paramount in developing an analytical tool suitable for (bio)sensing applications.

The search for efficient luminescent nanoprobes has spread out with the development of life science and nanomedicine. Among the different types of optical contrast agents, nanomaterials that can be excited by a two-photon process in the near infrared (NIR) region are particularly interesting as they allow for a better spatial resolution due to the quadratic nature of the excitation process and prevent the biological tissues from degradation [1]. Such excitation can produce either Second Harmonic Generation (SHG - if the compound is non-centrosymmetric) or fluorescence excited by two photons (such as up-conversion (UC)). SHG and fluorescence mechanisms are very different in terms of emission dynamics, polarization sensitivity, nanoparticle size dependency and are generally used independently in bioimaging techniques.
We here report the possibility to simultaneously exploit both mechanisms (SHG and UC) in Er³⁺-doped lanthanum iodate (α-La(IO₃)₃) nanoparticles (NPs), paving the way to new multiphoton microscopy approaches. α-La(IO₃)₃ NPs were synthesized using a microwave-assisted hydrothermal process. A tight control of the synthesis conditions (temperature, pressure, stoichiometry) is necessary to avoid the formation of multiple iodate polymorphs [2]. Various techniques (Electron Microscopy, Dynamic Light scattering) consistently indicate an average NP size of 50 ± 10 nm. SHG signal of NPs dispersed in solution was measured by the Hyper Raleigh Scattering technique [3], allowing for quantitative measurement of the average nonlinear optical coefficient: <d> ~ 8 pm V^-1, a value comparable to the one obtained for bulk α-La(IO₃)₃ [4]. When doped with Er³⁺, up-conversion emission, mainly centered at 550 nm, is also detected under a single excitation at either 800 nm or 980 nm. Both SHG and UC emission signals are thus observed from Er³⁺-doped α-La(IO₃)₃ NPs with an excitation in the first NIR biological transparency window [5].

[1] A. Rogov, M. Irondelle, F.R. Gomes, J. Bode, D. Staedler, S. Passemard, S. Courvoisier, Y. Yamamoto, F. Waharte, D. Ciepielewski, P. Rideau, S. Gerber-Lemaire, F. Alves, J. Salamero, L. Luigi Bonacina, J.P. Wolf, ACS Photonics (2015) 2, 1416
[2] Y. Suffren, O. Leynaud, P. Plaindoux, A. Brenier, I. Gautier-Luneau, Inorg. Chem. (2016) 55, 11264
[3] C. Joulaud, Y. Mugnier, G. Djanta, M. Dubled, J.C Marty, C. Galez, J.P Wolf, L. Bonacina, R. Le Dantec, J. Nanobiotechnology (2013) 11, S8
[4] K.M. Ok, P.S. Halasyamani, Inorg. Chem. 44 (2005) 9353
[5] S. Regny, J. Riporto, Y. Mugnier, R. Le Dantec, I. Gautier-Luneau, G. Dantelle, submitted