Nanophotonics & Quantum Optics, Biophysics & Medical Physics
The Lewis laboratory pioneered this field of optics, which has produced the highest optical resolution that has ever been obtained. All optical microscopes work in the far-field, where the optical element is held many wavelengths away from the object that is to be imaged. The near-field, on the other hand, is a few nanometers from the point in the object that has to be imaged and near-field imaging requires an optical probe of nanometer dimensionality to be brought within the spatially confined region that is to be interrogated. For such near-field imaging our group introduced the glass pulling technology that is used in most near-field imaging today. Near-field imaging is making significant impact in many fields including microelectronics, biophysics, genertics, data storage etc. All of these fields today require high-resolution optical imaging beyond the limit of lens-based optics. Near-field optics is also becoming the tool in defect inspection of telecommunication components that are crucial in the photonics revolution that is occurring today. The laboratory is very active in this area both in terms of understanding lasers for wavelength division multiplexing (WDM), optical multiplexers, de-multiplexers, optical switches, waveguides, couplers and optical amplifiers. The lab is also involved in developing embedded sensors for optical communications components based on near-field optical principles to monitor routing difficulties in telecommunication networks. Furthermore, today the laboratory is actively investigating using near-field optics data in combination with far-field optics to produce 3D far-field optical imaging with super-resolutions that have never been possible before. This later research, which is being done with Professor Nissim Ben-Yosef will provide new directions to break the diffraction barrier in far-field optical microscopy.
The growth of near-field optics resulted from the introduction in 1986 by Harootunian et al  of glass pulling technology for the formation of near-field optical elements. Although the method has resulted in near-field optical elements of choice and in force sensors with unique properties for studying proteins that are not found in conventional silicon cantilevers for force sensing , the utility of this methodology for generating a variety of nanotools with single and multichannel capabilities has not been fully appreciated. A nanotool kit has been generated based on glass pulling with single and multichannel micropipettes with the channels either filled with metal wires or left empty for the delivery or the removal of material. The structures that have been formed are nanopens , nanotweezers, nanoheaters, a voltage based molecular manipulator of DNA and voltage probe, a multichannel nanoparticle generator etc. In all cases these nanoglass tools can be combined with simultaneous force sensing and in many instances can have additional attributes including near-field optical and electrochemical sensing of surface alterations. In addition, these tips have allowed for novel active light sources to be generated. Finally, the nanotweezers which are based on dual channel tapered electrically isolated Pt metal wires in tapered cantilevered dual channel glass micropipettes can be employed either as tweezers (see Figure A and B) or simultaneous force and thermal resistive and electrical resistance probes (see Figure D, E and F). The data in Figure C, D, E and F were obtained on chemical mechanically polished (CMP) static random access memory (SRAM) chips produced with 0.18 micron design rules.
The Lewis laboratory has a long-standing interest in the unique biological membrane called the purple membrane. The purple membrane is the only crystalline membrane found in nature. It is formed in the membrane of the bacterium Halobacterium solanarium when the oxygen concentration is low. It is composed of a single protein molecule called bacteriorhodopsin (bR). bR is related to the visual pigment rhodopsin that is central to all of vision. Nonetheless, it is also of extreme importance in its own right since it is a light driven proton pump and the generation of proton gradients across cellular membranes are the general mechanism through which biological systems store light or respiratory energy. Even though the ultimate biological function of bR, that of an energy converter, and rhodopsin, that of a quantum detector are certainly different, it is generally believed that the primary action of light that initiates the physiological function of these proteins is similar. The classical and generally accepted mechanism is that the absorption of light in the polyene causes a photochemical structural alteration or isomerization in the light absorbing protein component, retinal, and this subsequently alters the protein and leads it into its physiologically active state for visual response. About 20 years ago we proposed an alternate model for this process. This model evolved out of trying to understand the characteristics of our observation of the first light emission from a rhodopsin-like protein. In this alternate model of retinal protein activation, light was hypothesized to induce a large charge redistribution. The principle activity of the Lewis group in this area are tests of this model. Results produced by the group has substantiated many of the aspects of the alternate model which is being accepted by the rest of the scientific community based on these results.
A simple, novel method has been developed to electrically emulate the action of pulsed lasers such as the Er:YAG and ArF lasers in vitreoretinal surgery. The method is based on delivering transient electrical pulses through tapered glass structures has the potential to compete with the ultramicrosurgical action of laser techniques such as the ArF [1-3] and Er:YAG  lasers that have been able to effectively perform in areas of microsurgery, such as vitreoretinal surgery, that require ultraprecise tissue cutting with minimal collateral damage. Microelectrodes with special designs have been prepared based on glass pulling technologies developed in our laboratory  for point thermocouples, heaters and near-field optical elements that can also act as optical coax structures. These structures have one or more metal wires in a tapered glass structure which can be externally coated with an additional metal. Such structures can also be used as a point source for the delivery of transient electrical pulses to highly local regions of convoluted tissues. For various electrode configurations the minimal safe distance (minimal distance between the point of the cutting tool and the region of the tissue for which there is no observable damage) will be reported. It will be shown that results obtained in animal studies and in an ongoing human trial of this technology indicate that this methodology can achieve, with lower pulse energies, cutting rates that are similar to laser systems that have been shown to have exceptional ultramicosurgical abilities in vitreoretinal surgery. The technique has significant potential for replacing ArF and Er:YAG laser techniques in ultramicrosurgical applications. In addition to the above, spectral confinement of tissue alteration is used as a proposed treatment for age related macular degeneration, the leading cause of blindness in the world today. There are many clinical conditions that require highly localized tissue alteration at specified depths without any affect on the overlying tissue. An excellent example of this is the problem of Age Related Macular Degeneration. This is one of the major problems leading to blindness today. In 70 % of the population, as they become older, there is a development behind the retina of yellow droplets. The yellow pigments are now known to contain a molecular species that has as part of its molecular structure the retinal chromophore. This is the origin of the yellow pigment. In approximately 30 % of the 70 % of the population that develop these pigment droplets, there is a definitely higher propensity for the special pigment molecules to lead to a damaging effect on the retina that lies above the pigment containing vesicles and this leads to blindness. It is generally thought that the origin of the damage results from the light that goes through the retina and reaches the yellow droplet molecules. The act of absorption of the light, which is a simple byproduct of the everyday act of seeing, produces a molecule called singlet oxygen from the surrounding oxygen that are all around these droplets. The singlet oxygen is a very reactive species and this molecule then reacts with the surrounding tissue, including the retinal tissue to slowly destroy and degenerate it, thus leading to blindness. If there was a way to ablate away these droplet molecules and locally destroy them there would be a way to retard the progress of the disease. We have shown that using two photon absorption stimulated with a femtosecond laser the droplets can be selectively bleached without observable damage to the overlying tissue.
Electrophysiology of the nematode C. elegans has the potential to bridge the wealth of information on the molecular biology and anatomy of this organism with the responses of selected cells and cellular neural networks associated with behavioral responses. In the past this has been impossible to accomplish for two reasons, first, the cells are simply too remote and too small to be probed by conventional methods of electrophysiology. Second, there has been no approach to developing learning protocols in this animal inspite of extensive genetic mutants that exist for various behavioral characteristics. Research in the laboratory of Aaron Lewis has achieved a breakthrough that not only allows electrical measurements at selected sites in selected neurons of C. elegans but also allows for the development for protocols of associative learning in this important model system that is so well understood genetically This breakthrough is based on several years of developments in the Lewis laboratory that has shown that the non-linear optical phenomenon of second harmonic generation (SHG) is a highly sensitive monitor of membrane potential [1-4]. SHG employs infrared or near-infrared photons from a short pulsed laser to interact with asymmetrically distributed molecules to produce light at a frequency that is double the incident fundamental laser frequency. Thus, infrared photons at a 1 micron fundamental wavelength would produce a second harmonic (SH) signal in the green at 0.5 microns. The intensity of the SHG depends on the dipole that is induced in the asymmetrically distributed molecule by the pulse of laser light and this dipole is either enhanced or reduced by membrane potential. Therefore, if a chromophore is asymmetrically associated with a membrane and this chromophore has a large induced dipole relative to the surrounding membrane lipids and proteins then this probe molecule will be selectively observed in the SH image  and will be able to selectively monitor the membrane potential at that site. Within the last year the laboratory has shown that the non-linear optical phenomenon of second harmonic generation (SHG) can be detected using green fluorescent protein (GFP) expressed through mutations in selected cells of living C. elegans . Alterations in the SHG signal as a result of receptor ligand interactions and mechanical stimulation of the mechanosensory cells demonstrate that this signal is very sensitive to membrane potential . The results suggest that this approach to membrane potential measurements in C. elegans and in other biological systems could effectively couple data on specific cells with functional responses that are associated with behavioral and sensory processes. To relate these measurements to the behavioral and sensory processes in this animal, the Lewis laboratory has developed a very unique system for scanned probe microscopy based on tapered cantilevered optical fibers or tapered cantilevered micropipettes . This system is fully integrated into the second harmonic microscope that has been developed by the laboratory. Such a system is being employed to combine point mechanical stimulation with point odor sensing  and/or point thermal excitation. The combination is being used for developing learning protocols for C. elegans while monitoring with GFP genetic labeling at specific sites the membrane potential and the receptor potential in specific neurons that are part of selected neural networks in this worm and in numerous behavioral mutants that have been identified. The results should lead to important developments in computational neurobiology.
A digital, CCD, optical image of C. elegans with a cantilevered optical fiber in contact with a 30 nm region of the animal. Illumination through the optical fiber precisely locates the pixel on the digital image that is associated with the region where pressure is being imposed on the animal. The square box indicates the extent of the a scan of the tip where the distribution of mechanoreceptors is probed. Forces from nanonewtons can be imposed. A force induced optically detected receptor potential has been detected and the results provide critical information on the mechanism of force sensory perception in this system.