33 results
(View BibTeX file of all listed publications)
2022
Magnetic Micro-/Nanopropellers for Biomedicine
Qiu, T., Jeong, M., Goyal, R., Kadiri, V., Sachs, J., Fischer, P.
In Field-Driven Micro and Nanorobots for Biology and Medicine, pages: 389-410, 16, (Editors: Sun, Y. and Wang, X. and Yu, J.), Springer, Cham, 2022 (inbook)
In nature, many bacteria swim by rotating their helical flagella. A particularly promising class of artificial micro- and nano-robots mimic this propeller-like propulsion mechanism to move through fluids and tissues for applications in minimally-invasive medicine. Several fundamental challenges have to be overcome in order to build micro-machines that move similar to bacteria for in vivo applications. Here, we review recent advances of magnetically-powered micro-/nano-propellers. Four important aspects of the propellers – the geometrical shape, the fabrication method, the generation of magnetic fields for actuation, and the choice of biocompatible magnetic materials – are highlighted. First, the fundamental requirements are elucidated that arise due to hydrodynamics at low Reynolds (Re) number. We discuss the role that the propellers’ shape and symmetry play in realizing effective propulsion at low Re. Second, the additive nano-fabrication method Glancing Angle Deposition is discussed as a versatile technique to quickly grow large numbers of designer nano-helices. Third, systems to generate rotating magnetic fields via permanent magnets or electromagnetic coils are presented. And finally, the biocompatibility of the magnetic materials is discussed. Iron-platinum is highlighted due to its biocompatibility and its superior magnetic properties, which is promising for targeted delivery, minimally-invasive magnetic nano-devices and biomedical applications.
2020
Evaluation of nanorobots for targeted delivery into the retina
Schnichels, S., Goyal, R., Hurst, F., Ziemsen, F., Qiu, T., Fischer, P.
61, pages: 1355, Investigative Ophthalmology & Visual Science,The Association for Research in Vision and Ophthalmology, June 2020 (conference)
A major challenge in the treatment of eye diseases in general and retinal diseases in particular, is to deliver drugs to their target sites. Traditional intravitreal injection is based on random, passive diffusion of molecules. In order to specifically address certain structures of the retina, the use of novel particles from biomaterial research promises a more targeted application. The major challenge for such particles is the narrow macromolecular matrix of ocular tissue (including the vitreous body), which acts as a barrier and prevents the penetration of particles. Novel nanorobots from material research - more precisely: nanopropellers - that can be actively controlled through the vitreous body to reach the retina present a chance to reach desired targets in the retina.
Acoustofluidic Tweezers for the 3D Manipulation of Microparticles
Guo, X., Ma, Z., Goyal, R., Jeong, M., Pang, W., Fischer, P., Dian, X., Qiu, T.
2020 IEEE International Conference on Robotics and Automation (ICRA 2020), pages: 11392-11397, IEEE, Piscataway, NJ, IEEE International Conference on Robotics and Automation (ICRA 2020), 2020 (conference)
Non-contact manipulation is of great importance in the actuation of micro-robotics. It is challenging to contactless manipulate micro-scale objects over large spatial distance in fluid. Here, we describe a novel approach for the dynamic position control of microparticles in three-dimensional (3D) space, based on high-speed acoustic streaming generated by a micro-fabricated gigahertz transducer. Due to the vertical lifting force and the horizontal centripetal force generated by the streaming, microparticles are able to be stably trapped at a position far away from the transducer surface, and to be manipulated over centimeter distance in all three directions. Only the hydrodynamic force is utilized in the system for particle manipulation, making it a versatile tool regardless the material properties of the trapped particle. The system shows high reliability and manipulation velocity, revealing its potentials for the applications in robotics and automation at small scales.
Soft Microrobots Based on Photoresponsive Materials
In Mechanically Responsive Materials for Soft Robotics, pages: 327-362, (Editors: Koshima, Hideko), Wiley-VCH, Weinheim, 2020 (incollection)
2019
Soft Continuous Surface for Micromanipulation driven by Light-controlled Hydrogels
Choi, E., Jeong, H., Qiu, T., Fischer, P., Palagi, S.
4th IEEE International Conference on Manipulation, Automation and Robotics at Small Scales (MARSS), July 2019 (conference)
Remotely controlled, automated actuation and manipulation at the microscale is essential for a number of micro-manufacturing, biology, and lab-on-a-chip applications. To transport and manipulate micro-objects, arrays of remotely controlled micro-actuators are required, which, in turn, typically require complex and expensive solid-state chips. Here, we show that a continuous surface can function as a highly parallel, many-degree of freedom, wirelessly-controlled microactuator with seamless deformation. The soft continuous surface is based on a hydrogel that undergoes a volume change in response to applied light. The fabrication of the hydrogels and the characterization of their optical and thermomechanical behaviors are reported. The temperature-dependent localized deformation of the hydrogel is also investigated by numerical simulations. Static and dynamic deformations are obtained in the soft material by projecting light fields at high spatial resolution onto the surface. By controlling such deformations in open loop and especially closed loop, automated photoactuation is achieved. The surface deformations are then exploited to examine how inert microbeads can be manipulated autonomously on the surface. We believe that the proposed
approach suggests ways to implement universal 2D micromanipulation schemes that can be useful for automation in microfabrication and lab-on-a-chip applications.
Soft Phantom for the Training of Renal Calculi Diagnostics and Lithotripsy
Li., D., Suarez-Ibarrola, R., Choi, E., Jeong, M., Gratzke, C., Miernik, A., Fischer, P., Qiu, T.
41st Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), July 2019 (conference)
Organ models are important for medical training and surgical planning. With the fast development of additive fabrication technologies, including 3D printing, the fabrication of 3D organ phantoms with precise anatomical features becomes possible. Here, we develop the first high-resolution kidney
phantom based on soft material assembly, by combining 3D printing and polymer molding techniques. The phantom exhibits both the detailed anatomy of a human kidney and the elasticity of soft tissues. The phantom assembly can be separated into two parts on the coronal plane, thus large renal calculi are readily placed at any desired location of the calyx. With our sealing method, the assembled phantom withstands a hydraulic pressure that is four times the normal intrarenal pressure, thus it allows the simulation of medical procedures under realistic pressure conditions. The medical diagnostics of the renal calculi is performed by multiple imaging modalities, including X-ray, ultrasound imaging and endoscopy. The endoscopic lithotripsy is also successfully performed on the phantom. The use of a multifunctional soft phantom assembly thus shows great promise for the simulation of minimally invasive medical procedures under realistic conditions.
A Magnetic Actuation System for the Active Microrheology in Soft Biomaterials
Jeong, M., Choi, E., Li., D., Palagi, S., Fischer, P., Qiu, T.
4th IEEE International Conference on Manipulation, Automation and Robotics at Small Scales (MARSS), July 2019 (conference)
Microrheology is a key technique to characterize soft materials at small scales. The microprobe is wirelessly actuated and therefore typically only low forces or torques can be applied, which limits the range of the applied strain. Here, we report a new magnetic actuation system for microrheology consisting of an array of rotating permanent magnets, which achieves a rotating magnetic field with a spatially homogeneous high field strength of ~100 mT in a working volume of ~20×20×20 mm3. Compared to a traditional electromagnetic coil system, the permanent magnet assembly is portable and does not require cooling, and it exerts a large magnetic torque on the microprobe that is an order of magnitude higher than previous setups. Experimental results demonstrate that the measurement
range of the soft gels’ elasticity covers at least five orders of magnitude. With the large actuation torque, it is also possible to study the fracture mechanics of soft biomaterials at small scales.
HPLC separation of ligand-exchanged gold clusters with atomic precision
Itzigehl, Selina
Univ. of Stuttgart, 2019 (thesis)
2018
Gait learning for soft microrobots controlled by light fields
Rohr, A. V., Trimpe, S., Marco, A., Fischer, P., Palagi, S.
In International Conference on Intelligent Robots and Systems (IROS) 2018, pages: 6199-6206, Piscataway, NJ, USA, International Conference on Intelligent Robots and Systems 2018, October 2018 (inproceedings)
Soft microrobots based on photoresponsive materials and controlled by light fields can generate a variety of different gaits. This inherent flexibility can be exploited to maximize their locomotion performance in a given environment and used to adapt them to changing environments. However, because of the lack of accurate locomotion models, and given the intrinsic variability among microrobots, analytical control design is not possible. Common data-driven approaches, on the other hand, require running prohibitive numbers of experiments and lead to very sample-specific results. Here we propose a probabilistic learning approach for light-controlled soft microrobots based on Bayesian Optimization (BO) and Gaussian Processes (GPs). The proposed approach results in a learning scheme that is highly data-efficient, enabling gait optimization with a limited experimental budget, and robust against differences among microrobot samples. These features are obtained by designing the learning scheme through the comparison of different GP priors and BO settings on a semisynthetic data set. The developed learning scheme is validated in microrobot experiments, resulting in a 115% improvement in a microrobot’s locomotion performance with an experimental budget of only 20 tests. These encouraging results lead the way toward self-adaptive microrobotic systems based on lightcontrolled soft microrobots and probabilistic learning control.
Nanoscale robotic agents in biological fluids and tissues
Palagi, S., Walker, D. Q. T., Fischer, P.
In The Encyclopedia of Medical Robotics, 2, pages: 19-42, 2, (Editors: Desai, J. P. and Ferreira, A.), World Scientific, October 2018 (inbook)
Nanorobots are untethered structures of sub-micron size that can be controlled in a non-trivial way. Such nanoscale robotic agents are envisioned to revolutionize medicine by enabling minimally invasive diagnostic and therapeutic procedures. To be useful, nanorobots must be operated in complex biological fluids and tissues, which are often difficult to penetrate. In this chapter, we first discuss potential medical applications of motile nanorobots. We briefly present the challenges related to swimming at such small scales and we survey the rheological properties of some biological fluids and tissues. We then review recent experimental results in the development of nanorobots and in particular their design, fabrication, actuation, and propulsion in complex biological fluids and tissues. Recent work shows that their nanoscale dimension is a clear asset for operation in biological tissues, since many biological tissues consist of networks of macromolecules that prevent the passage of larger micron-scale structures, but contain dynamic pores through which nanorobots can move.
Soft Miniaturized Linear Actuators Wirelessly Powered by Rotating Permanent Magnets
Qiu, T., Palagi, S., Sachs, J., Fischer, P.
In 2018 IEEE International Conference on Robotics and Automation (ICRA), 2018 IEEE International Conference on Robotics and Automation (ICRA), pages: 3595-3600, Piscataway, NJ, USA, May 2018 (inproceedings)
Wireless actuation by magnetic fields allows for the operation of untethered miniaturized devices, e.g. in biomedical applications. Nevertheless, generating large controlled forces over relatively large distances is challenging. Magnetic torques are easier to generate and control, but they are not always suitable for the tasks at hand. Moreover, strong magnetic fields are required to generate a sufficient torque, which are difficult to achieve with electromagnets. Here, we demonstrate a soft miniaturized actuator that transforms an externally applied magnetic torque into a controlled linear force. We report the design, fabrication and characterization of both the actuator and the magnetic field generator. We show that the magnet assembly, which is based on a set of rotating permanent magnets, can generate strong controlled oscillating fields over a relatively large workspace. The actuator, which is 3D-printed, can lift a load of more than 40 times its weight. Finally, we show that the actuator can be further miniaturized, paving the way towards strong, wirelessly powered microactuators.
2017
Locomotion of light-driven soft microrobots through a hydrogel via local melting
Palagi, S., Mark, A. G., Melde, K., Qiu, T., Zeng, H., Parmeggiani, C., Martella, D., Wiersma, D. S., Fischer, P.
In 2017 International Conference on Manipulation, Automation and Robotics at Small Scales (MARSS), pages: 1-5, Piscataway, NJ, USA, July 2017 (inproceedings)
Soft mobile microrobots whose deformation can be directly controlled by an external field can adapt to move in different environments. This is the case for the light-driven microrobots based on liquid-crystal elastomers (LCEs). Here we show that the soft microrobots can move through an agarose hydrogel by means of light-controlled travelling-wave motions. This is achieved by exploiting the inherent rise of the LCE temperature above the melting temperature of the agarose gel, which facilitates penetration of the microrobot through the hydrogel. The locomotion performance is investigated as a function of the travelling-wave parameters, showing that effective propulsion can be obtained by adapting the generated motion to the specific environmental conditions.
A Wirelessly Actuated Robotic Arm for Endoscopy
Qiu, T., Palagi, S., Adams, F., Wetterauer, U., Miernik, A., Fischer, P.
pages: 29, The Hamlyn Symposium on Medical Robotics, June 2017 (conference)
Endoscopy enables a number of important minimally invasive medical procedures. Current commercial flexible endoscopes with small diameter often have only one bending section near the tip with only one degree of freedom (DoF). This strongly limits the area that can be reached by the endoscope. Researchers have made many efforts to develop multi-DoF miniaturized robotic endoscopes that can be controlled in multiple bending sections and that still possess an overall size small enough to enter the body through a single-port [1]. Robotic endoscopes are normally actuated by tendons [2], pneumatics [3] or the rotation of concentric tubes [4]. In comparison to these tethered approaches, wireless actuation allows for more flexibility and easier miniaturization.
Ultrasound is a promising way to transfer power wirelessly in vivo. Recently, we reported an active surface actuator that directly converts ultrasound power into mechanical work via acoustic streaming from an array of micro-bubbles [5]. Here, we apply such wireless actuators to a miniaturized robotic arm, which works as an endoscopic tip (Fig. 1). The active surfaces consisting of arrays of micro-bubbles are attached to the arm and generate streaming of the adjacent fluid under ultrasound excitation. The recoil force actuates the arm. Different bubble sizes are addressed by different ultrasound frequencies, thus multiple DoFs are realized by the arm and require only one tunable ultrasound source.
Chapter 8 - Micro- and nanorobots in Newtonian and biological viscoelastic fluids
Palagi, S., (Walker) Schamel, D., Qiu, T., Fischer, P.
In Microbiorobotics, pages: 133 - 162, 8, Micro and Nano Technologies, Second edition, Elsevier, Boston, March 2017 (incollection)
Swimming microorganisms are a source of inspiration for small scale robots that are intended to operate in fluidic environments including complex biomedical fluids. Nature has devised swimming strategies that are effective at small scales and at low Reynolds number. These include the rotary corkscrew motion that, for instance, propels a flagellated bacterial cell, as well as the asymmetric beat of appendages that sperm cells or ciliated protozoa use to move through fluids. These mechanisms can overcome the reciprocity that governs the hydrodynamics at small scale. The complex molecular structure of biologically important fluids presents an additional challenge for the effective propulsion of microrobots. In this chapter it is shown how physical and chemical approaches are essential in realizing engineered abiotic micro- and nanorobots that can move in biomedically important environments. Interestingly, we also describe a microswimmer that is effective in biological viscoelastic fluids that does not have a natural analogue.
Wireless micro-robots for endoscopic applications in urology
Adams, F., Qiu, T., Mark, A. G., Melde, K., Palagi, S., Miernik, A., Fischer, P.
In Eur Urol Suppl, 16(3):e1914, March 2017 (inproceedings)
Endoscopy is an essential and common method for both diagnostics and therapy in Urology. Current flexible endoscope is normally cable-driven, thus it is hard to be miniaturized and its reachability is restricted as only one bending section near the tip with one degree of freedom (DoF) is allowed. Recent progresses in micro-robotics offer a unique opportunity for medical inspections in minimally invasive surgery. Micro-robots are active devices that has a feature size smaller than one millimeter and can normally be actuated and controlled wirelessly. Magnetically actuated micro-robots have been demonstrated to propel through biological fluids.Here, we report a novel micro robotic arm, which is actuated wirelessly by ultrasound. It works as a miniaturized endoscope with a side length of ~1 mm, which fits through the 3 Fr. tool channel of a cystoscope, and successfully performs an active cystoscopy in a rabbit bladder.
Propulsion of magnetic colloids at low Reynolds number
Segreto, Nico
Univ. of Stuttgart, 2017 (thesis)
2016
Soft continuous microrobots with multiple intrinsic degrees of freedom
Palagi, S., Mark, A. G., Melde, K., Zeng, H., Parmeggiani, C., Martella, D., Wiersma, D. S., Fischer, P.
In 2016 International Conference on Manipulation, Automation and Robotics at Small Scales (MARSS), pages: 1-5, Piscataway, NJ, USA, July 2016 (inproceedings)
One of the main challenges in the development of microrobots, i.e. robots at the sub-millimeter scale, is the difficulty of adopting traditional solutions for power, control and, especially, actuation. As a result, most current microrobots are directly manipulated by external fields, and possess only a few passive degrees of freedom (DOFs). We have reported a strategy that enables embodiment, remote powering and control of a large number of DOFs in mobile soft microrobots. These consist of photo-responsive materials, such that the actuation of their soft continuous body can be selectively and dynamically controlled by structured light fields. Here we use finite-element modelling to evaluate the effective number of DOFs that are addressable in our microrobots. We also demonstrate that by this flexible approach different actuation patterns can be obtained, and thus different locomotion performances can be achieved within the very same microrobot. The reported results confirm the versatility of the proposed approach, which allows for easy application-specific optimization and online reconfiguration of the microrobot's behavior. Such versatility will enable advanced applications of robotics and automation at the micro scale.
Wireless actuator based on ultrasonic bubble streaming
Qiu, T., Palagi, S., Mark, A. G., Melde, K., Fischer, P.
In 2016 International Conference on Manipulation, Automation and Robotics at Small Scales (MARSS), pages: 1-5, Piscataway, NJ, USA, July 2016 (inproceedings)
Miniaturized actuators are a key element for the manipulation and automation at small scales. Here, we propose a new miniaturized actuator, which consists of an array of micro gas bubbles immersed in a fluid. Under ultrasonic excitation, the oscillation of micro gas bubbles results in acoustic streaming and provides a propulsive force that drives the actuator. The actuator was fabricated by lithography and fluidic streaming was observed under ultrasound excitation. Theoretical modelling and numerical simulations were carried out to show that lowing the surface tension results in a larger amplitude of the bubble oscillation, and thus leads to a higher propulsive force. Experimental results also demonstrate that the propulsive force increases 3.5 times when the surface tension is lowered by adding a surfactant. An actuator with a 4×4 mm 2 surface area provides a driving force of about 0.46 mN, suggesting that it is possible to be used as a wireless actuator for small-scale robots and medical instruments.
Auxetic Metamaterial Simplifies Soft Robot Design
Mark, A. G., Palagi, S., Qiu, T., Fischer, P.
In 2016 IEEE Int. Conf. on Robotics and Automation (ICRA), pages: 4951-4956, Piscataway, NJ, USA, May 2016 (inproceedings)
Soft materials are being adopted in robotics in order to facilitate biomedical applications and in order to achieve simpler and more capable robots. One route to simplification is to design the robot's body using `smart materials' that carry the burden of control and actuation. Metamaterials enable just such rational design of the material properties. Here we present a soft robot that exploits mechanical metamaterials for the intrinsic synchronization of two passive clutches which contact its travel surface. Doing so allows it to move through an enclosed passage with an inchworm motion propelled by a single actuator. Our soft robot consists of two 3D-printed metamaterials that implement auxetic and normal elastic properties. The design, fabrication and characterization of the metamaterials are described. In addition, a working soft robot is presented. Since the synchronization mechanism is a feature of the robot's material body, we believe that the proposed design will enable compliant and robust implementations that scale well with miniaturization.
Towards Photo-Induced Swimming: Actuation of Liquid Crystalline Elastomer in Water
cerretti, G., Martella, D., Zeng, H., Parmeggiani, C., Palagi, S., Mark, A. G., Melde, K., Qiu, T., Fischer, P., Wiersma, D.
In Proc. of SPIE 9738, pages: Laser 3D Manufacturing III, 97380T, Bellingham, Washington, April 2016 (inproceedings)
Liquid Crystalline Elastomers (LCEs) are very promising smart materials that can be made sensitive to different external stimuli, such as heat, pH, humidity and light, by changing their chemical composition. In this paper we report the implementation of a nematically aligned LCE actuator able to undergo large light-induced deformations. We prove that this property is still present even when the actuator is submerged in fresh water. Thanks to the presence of azo-dye moieties, capable of going through a reversible trans-cis photo-isomerization, and by applying light with two different wavelengths we managed to control the bending of such actuator in the liquid environment. The reported results
represent the first step towards swimming microdevices powered by light.
2015
3D-printed Soft Microrobot for Swimming in Biological Fluids
Qiu, T., Palagi, S., Fischer, P.
In Conf. Proc. IEEE Eng. Med. Biol. Soc., pages: 4922-4925, Piscataway, NJ, USA, August 2015 (inproceedings)
Microscopic artificial swimmers hold the potential to enable novel non-invasive medical procedures. In order to ease their translation towards real biomedical applications, simpler designs as well as cheaper yet more reliable materials and fabrication processes should be adopted, provided that the functionality of the microrobots can be kept. A simple single-hinge design could already enable microswimming in non-Newtonian fluids, which most bodily fluids are. Here, we address the fabrication of such single-hinge microrobots with a 3D-printed soft material. Firstly, a finite element model is developed to investigate the deformability of the 3D-printed microstructure under typical values of the actuating magnetic fields. Then the microstructures are fabricated by direct 3D-printing of a soft material and their swimming performances are evaluated. The speeds achieved with the 3D-printed microrobots are comparable to those obtained in previous work with complex fabrication procedures, thus showing great promise for 3D-printed microrobots to be operated in biological fluids.
2014
3D nanofabrication on complex seed shapes using glancing angle deposition
Hyeon-Ho, J., Mark, A. G., Gibbs, J. G., Reindl, T., Waizmann, U., Weis, J., Fischer, P.
In 2014 IEEE 27th International Conference on Micro Electro Mechanical Systems (MEMS), pages: 437-440, Piscataway, NJ, USA, January 2014 (inproceedings)
Three-dimensional (3D) fabrication techniques promise new device architectures and enable the integration of more components, but fabricating 3D nanostructures for device applications remains challenging. Recently, we have performed glancing angle deposition (GLAD) upon a nanoscale hexagonal seed array to create a variety of 3D nanoscale objects including multicomponent rods, helices, and zigzags [1]. Here, in an effort to generalize our technique, we present a step-by-step approach to grow 3D nanostructures on more complex nanoseed shapes and configurations than before. This approach allows us to create 3D nanostructures on nanoseeds regardless of seed sizes and shapes.
Active Microrheology of the Vitreous of the Eye applied to Nanorobot Propulsion
Qiu, T., Schamel, D., Mark, A. G., Fischer, P.
In 2014 IEEE INTERNATIONAL CONFERENCE ON ROBOTICS AND AUTOMATION (ICRA), pages: 3801-3806, IEEE International Conference on Robotics and Automation ICRA, Piscataway, NJ, USA, 2014, Best Automation Paper Award – Finalist. (inproceedings)
Biomedical applications of micro or nanorobots require active movement through complex biological fluids. These are generally non-Newtonian (viscoelastic) fluids that are characterized by complicated networks of macromolecules that have size-dependent rheological properties. It has been suggested that an untethered microrobot could assist in retinal surgical procedures. To do this it must navigate the vitreous humor, a hydrated double network of collagen fibrils and high molecular-weight, polyanionic hyaluronan macromolecules. Here, we examine the characteristic size that potential robots must have to traverse vitreous relatively unhindered. We have constructed magnetic tweezers that provide a large gradient of up to 320 T/m to pull sub-micron paramagnetic beads through biological fluids. A novel two-step electrical discharge machining (EDM) approach is used to construct the tips of the magnetic tweezers with a resolution of 30 mu m and high aspect ratio of similar to 17:1 that restricts the magnetic field gradient to the plane of observation. We report measurements on porcine vitreous. In agreement with structural data and passive Brownian diffusion studies we find that the unhindered active propulsion through the eye calls for nanorobots with cross-sections of less than 500 nm.
Best Automation Paper Award – Finalist.
2006
NONLINEAR OPTICAL PROPERTIES OF CHIRAL LIQUIDS Electric-dipolar pseudoscalars in nonlinear optics
Fischer, P., Champagne, B.
In NON-LINEAR OPTICAL PROPERTIES OF MATTER: FROM MOLECULES TO CONDENSED PHASES, 1, pages: 359-381, Challenges and Advances in Computational Chemistry and Physics, 2006 (incollection)
We give all overview of linear and nonlinear optical processes that can be specific to chiral molecules in isotropic media. Specifically, we discuss the pseudoscalars that underlie nonlinear optical activity and chiral frequency conversion processes in fluids. We show that nonlinear optical techniques open entirely new ways of exploring chirality: Sum-frequency-generation (SFG) at second-order and BioCARS at fourth-order arise in the electric-dipole approximation and do not require circularly polarized light to detect chiral molecules in solution. Here the frequency conversion in itself is a measure of chirality. This is in contrast to natural optical activity phenomena which are based on the interference of radiation from induced oscillating electric and magnetic dipoles, and which are observed as a differential response to right and left circularly polarized light. We give examples from our SFG experiments in optically active solutions and show how the application of an additional static electric field to sum-frequency generation allows the absolute configuration of the chiral solute to be determined via all electric-dipolar process. Results from ab initio calculations of the SFG pseudoscalar are presented for a number of chiral molecules