Surface plasmons (SPs) are surface charge density oscillations occuring at a metal/dieletric interface and are highly sensitive to refractive index variations adjacent to the surface. This sensitivity has been exploited successfully for chemical and biological assays. In these systems, a surface plasmon resonance (SPR)-based sensor detects temporal variations in the refractive index at a point. SPR has also been used in imaging systems where the spatial variations of refractive index in the sample provide the contrast mechanism. SPR imaging systems using high numerical aperture (NA) objective lenses have been designed to image adherent live cells with high magnification and near-diffraction limited spatial resolution. Addressing research questions in cell physiology and pharmacology often requires the development of a multimodal microscope where complementary information can be obtained. In this paper, we present the development of a multimodal microscope that combines SPR imaging with a number of additional imaging modalities including bright-field, epifluorescence, total internal reflection microscopy and SPR fluorescence microscopy. We used a high NA objective lens for SPR and TIR microscopy and the platform has been used to image live cell cultures demonstrating both fluorescent and label-free techniques. Both the SPR and TIR imaging systems feature a wide field of view (~300 µ m) that allows measurements from multiple cells whilst maintaining a resolution sufficient to image fine cellular processes. The capability of the platform to perform label-free functional imaging of living cells was demonstrated by imaging the spatial variations in contractions from stem cell-derived cardiomyocytes. This technique shows promise for non-invasive imaging of cultured cells over very long periods of time during development.

In order for the field of bioelectronics to make an impact on healthcare, there is an urgent requirement for the development of "wireless" electronic systems to both sense and actuate cell behaviour. Herein we report the first example of an innovative intracellular wireless electronic communication system. We demonstrate that chemistry can be electrically modulated in a "wireless" manner on the nanoscale at the surface of conductive nanoparticles uptaken by cells at unreported low potentials. The system is made functional by modifying gold nanoparticles incorporating a Zn-porphyrin, which are taken up by cells and are shown to be biocompatible. It is demonstrated the redox state of Zn-porphyrin modified gold nanoparticles is modulated and reported on fluorescently when applying an external electrical potential. This provides an attractive new "wireless" approach to develop novel bioelectronic devices for modulating and sensing cellular behaviour using intracellular monitoring. The field of bioelectronic medicine offers a new paradigm in therapeutic intervention 1, 2. The technology is in its infancy, but relies on the ability to merge electronic devices with biology to then be used to sense and actuate cell/tissue and organ behaviour 3. The key challenge in advancing the field further is to develop new non-invasive methods to both electrically sense and actuate cell 3 behaviour. Our group 4-6 and others 7-10 have pioneered new methods for electrically communicating with the internal environment of a cell via use of nanowire electrodes. However, these methods tend to be invasive in nature as they necessarily have to pierce the plasma membrane which can lead to cell perturbations 11, 12. In addition, these electrodes require physical electrical connectivity from inside of the cells to the outside, thus hindering their use in more complex biological environments. Therefore, an approach to addressing these issues is to develop novel wireless electronic systems for the development of intracellular sensors and actuators. The development of novel bioelectronics using such a wireless-electronic approach may subsequently enable significant advancements in the ability to use intracellular electronics to facilitate cell communication and actuation. Therefore, the aim of this work was to develop a new bioelectronic approach for sensing electrical changes in response to the application of an externally applied voltage inside biological cells, thereby offering the first example of a wireless electronic tool to modulate redox inside of cells 13-14. The work undertaken was inspired by the fields of bipolar electrochemistry and drug delivery. Bipolar electrochemistry (also known as wireless electrochemistry) relies on placing a conductive particle between feeder electrodes which have potential difference placed across them. This causes the conductive particle to polarise and in doing so, causes a potential difference between the electrolyte and poles of the particle, consequently providing the thermodyamic driving force required ...

We describe a rapid one-step method to biotinylate virtually any biological or non-biological surface. Contacting a solution of biotin-spacer-lipid constructs with a surface will form a coating within seconds on non-biological surfaces or within minutes on most biological membranes including membrane viruses. The resultant biotinylated surface can then be used to interact with avidinylated conjugates, beads, vesicles, surfaces or cells.

Sensitive detection of voltage transients using differential intensity surface plasmon resonance system. Optics Express, 25 (25). pp. 31552-31567. ISSN 1094-4087 Access from the University of Nottingham repository: http://eprints.nottingham.ac.uk/46901/8/oe-25-25-31552.pdf Copyright and reuse:The Nottingham ePrints service makes this work by researchers of the University of Nottingham available open access under the following conditions. This article is made available under the Creative Commons Attribution licence and may be reused according to the conditions of the licence. For more details see: http://creativecommons.org/licenses/by/2.5/ A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription. Abstract: This paper describes theoretical and experimental study of the fundamentals of using surface plasmon resonance (SPR) for label-free detection of voltage. Plasmonic voltage sensing relies on the capacitive properties of metal-electrolyte interface that are governed by electrostatic interactions between charge carriers in both phases. Externally-applied voltage leads to changes in the free electron density in the surface of the metal, shifting the SPR position. The study shows the effects of the applied voltage on the shape of the SPR curve. It also provides a comparison between the theoretical and experimental response to the applied voltage. The response is presented in a universal term that can be used to assess the voltage sensitivity of different SPR instruments. Finally, it demonstrates the capacity of the SPR system in resolving dynamic voltage signals; a detection limit of 10mV with a temporal resolution of 5ms is achievable. These findings pave the way for the use of SPR systems in the detection of electrical activity of biological cells. 56, 1495-1503 (2013). 34. R. Azzam and N. Bashara, Ellipsometry and polarized light (Elsevier science, 1987. 35. J. Zhang, T. Atay, and A. Nurmikko, "Optical detection of brain cell activity using plasmonic gold nanoparticles", Nano Lett. 9, 519-524 (2009 Düsseldorf, Germany, 15-20 September 2002, vol. 48 (Elsevier, 2003. Opt. 12, 555-563 (1973). 42. N. Tao, S. Boussaad, R. Huang, W.L.and Arechabaleta, and J. DÁgnese, "High resolution surface plasmon resonance spectroscopy," Rev. Sci. Instrum.70, 4656-4660 (1999). 43. Z. Kerner and T. Pajkossy, "On the origin of capacitance dispersion of rough electrodes," Electrochim. Acta 46, 207-211 (2000). 44. W. Wang, K. Foley, X. Shan, S. Wang, S. Eaton, V. J. Nagaraj, P. Wiktor, U. Patel, and N. Tao, "Single cells and intracellular processes studied by a plasmonic-based electrochemical impedance microscopy," Nat. Chem. 3, 249-255 (2011). 1997-2003 (2005). 46. C. Celedón, M. Flores, P. Häberle, and J. Valdés, "Surface roughness of thin gold films and its ef...

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