- Nano photonics,
- Diffusion reflection,
- Fluorescence lifetime,
- Fluorescence anisotropy,
- Time resolve measurements,
- Gold nanoparticles,
- Biomolecular imaging,
- Advanced Communication protocols,
- Telephony (PSTN, PLMN, Cellular – GSM, GPRS, UMTS, LTE, 5G, CDMA, 1X).
Fixler's lab deals with theoretical and practical models for reconstructing the optical properties of participating media by nano photonic tools. Our theory is based on a robust generalization of the diffusion theory; Gerchberg-Saxton algorithm; dipole-dipole approximation and other methods. On the practical side we use lasers, LEDs and microscopes. Human tissue is one of the most complex optical mediums since it is nonhomogeneous. Its optical properties are unknown and vary in different tissue areas and physiological states. Because of all of the above, in vivo imaging is a difficult task. In Dror Fixler’s lab we deal with this difficulty by focusing on detection rather than imaging. We use methods which probe the tissue properties by means of the diffusion reflection profile, adding nano particles as contrast agent, the full scattering profile and its isobaric point or iterative phase multiple measurement reconstruction techniques. Furthermore, we use changes in optical parameters, such as fluorescence life time and fluorescence anisotropy to probe the biological surroundings. In Dror’s lab we are able to fabricate Gold nano particles (spheres and rods), organic nano particles (Vitamin B12, Penicillin and Methylene Blue) as well as tissue like phantoms. The applications for these methods include diagnosis of diseases such as cancer and atherosclerosis, examination of different physiological parameters, visualizing enzyme activity and early stage cell mutation detection.
Full scattering profile for detecting physiological tissue properties
Light reflectance and transmission from soft tissue has been utilized in noninvasive clinical measurement devices such as the photoplethysmograph (PPG) and reflectance pulse oximeter. Most methods of near infrared (NIR) spectroscopy focus on the volume reflectance from a semi-infinite sample, while very few measure transmission.
We previously shown that examining the full scattering profile (FSP), which is the angular distribution of exiting photons, provides more comprehensive information when measuring from a cylindrical tissue, such as earlobe, fingertip and pinched tissue.
Furthermore a point was found, i.e. the iso-pathlength point (IPL point), which is not dependent on changes in the reduced scattering coefficient. The angle corresponding to this isobaric point linearly depends on the tissue diameter.
Personalizable theranostics making use of fluorescence characterizations upon coupling to gold nanoparticles
In this research, we are studying the effects of gold nanoparticles on fluorescent molecules in their close vicinity using time-domain fluorescence lifetime imaging microscopy. By conjugating the particles to the fluorophores, we are able to observe quenching or even enhancement of the fluorescence. Subsequently, we can also detect changes in the fluorescence lifetime corresponding to the degree of conjugation. The purpose of this study is then to improve medical imaging capabilities by exploring smart probes based on gold nanoparticles, which interact with biological inputs, such as enzymatic activity or pH changes relevant to the body, and undergo detectable transformations.
Diffusion reflection measurements of gold nanorods
Optical imaging provides powerful tools for investigating tissue structure and function. Tissue optical imaging technologies are generally discussed in two broad regimes, microscopic and macroscopic, while the last is highly investigated in the field of light-tissue interaction. Among the developed optical technologies for tissue investigation, the diffusion reflectance (DR) method provides a simple and safe imaging technology. However, the DR method suffers from low specificity and low signal-to-noise ratio (SNR), thus the extraction of the tissue properties is not an easy task. In our research, we use gold nanorods (GNRs) in DR spectroscopy. The GNRs present unique optical properties which enhance the scattering and absorption properties of a tissue. The GNRs can be easily targeted toward abnormal sites to improve the DR signal and to enable the distinguishing between the healthy and the abnormal sites in the tissue, with high specificity.
Noninvasive nanophotincs technique for detecting different materials within physiological substances
In recent years, many efforts have been made to find ways to infiltrate materials into the human body. In particular in the medical area, there is a great need to use topical medications instead of injections. The nanoparticles (NPs) advantages are their increased biological activity and penetration depth into human tissues. However, noninvasively determining the penetration depth of NPs in tissues is a challenge many researchers are facing. We have developed a novel noninvasive nanophotincs technique, i.e., iterative multi-plane optical property extraction (IMOPE), for detecting different materials within physiological substances by extracting the optical properties of a sample. The IMOPE is based on the iterative multi-plane Gerchberg-Saxton algorithm for reconstructing the reemitted light phase. Using the transmission and reflectance light signals we were able to detect organic NPs within tissues, the different milk components quantitative signature, the viability of different tissues and Methylene blue absorption capability and combining a small amount of gold nanorods we were able to distinguish between the femoral vein and other adjacent tissues.
Development of simple flow cytometry based approach to identify and differentiate between M1/M2 classes of macrophages by GNRs of different aspect ratio
Macrophages, one of the most important candidates of innate immune response, mainly, are the specialized differentiated form of circulating blood Monocytes with pronounced phagocytic activity and larger size. Now, these macrophages under some prevalence of microbial infections, inflammations and tissue damage readily get ‘activated’ upon exposure to different stimuli. These ‘activated macrophages’ can have two major phenotypes, M1 (classically activated) and M2 (alternatively activated). The normal ratio of M1/M2 macrophages of healthy individuals get changed in certain disease conditions because of a shift in the M1 to M2 or M2 to M1 macrophage population. It is not easy to detect the ratio of M1/M2 just only based on their surface markers. The recent advancement in NPs based approach to dodge with clinical issues has inspired several attempts to establish nano-madiated detection methods to deal with such issues. GNPs are very attractive due to their unique optical property, from the visible to the infrared (IR) region, which varies with the particle shape, size and structure. It has been reported that macrophages readily phagocytosed GNPs in a size depended manner. Even recent studies have shown some differentially uptake of GNRs of different aspect ratio by M1 and M2. Based on these findings, we wish to establish a novel, quick flow cytometry based detection of M1/M2 macrophages by gold nanorods of different aspect ratio.
Entangled-photon pairs with metallic nanoparticles
This research focuses on the interaction of entangled-photon pairs with metallic nanoparticles. The use of entangled-photons for light-matter interaction is a promising tool for various applications such as quantum calculation, quantum metrology etc. However, it is limited by the low flux of such pairs generated by common sources.
Therefore, we suggest the use of NPs for such interactions. NPs can be synthesized to exhibit extremely localized field enhancement. This phenomenon occurs at specific wavelength and is known as Localized Surface Plasmon Resonance. By tuning the size and shape of the NPs we wish to optimize their optical properties to achieve a high two-photon interaction cross-section and prove they're indeed advantageous for entangled-photons interactions.
Fluorescence lifetime and anisotropy
Fluorescence lifetime (FLT) imaging microscopy (FLIM) is a popular technique in medical diagnostics thanks to its unique sensitivity to a wide variety of physical and chemical features. Fluorophores are widely used for biomedical imaging, however their intensity measurements are exposed to artifacts, giving qualitive information only. In our lab we focus on FLIM and anisotropy that can reveal valuable information about the corresponding biomolecular carrier on or within a cell. FLIM provides a quantitative mean for probing changes in the local fluorophore's environment. FLT allows characterizing physiological states and distinguish between diseased and healthy biology substances due to an in the native environment. Measurements of time-resolved fluorescence anisotropy can probe changes in the size, shape, flexibility, and associative behavior of biomolecules and as such it can provide additional and complementary information.
Areas of Interest
Fixler's areas of interest include experimental studies of fluorescence lifetime and anisotropy decay; Fluorescence lifetime imaging (FLIM); Biological imaging based on fluorescence parameters; Methods of microscopy and super resolution. In addition, he is interested in core networks and protocols for wireless communications.
The group is particularly interested in expanding their research activities in the areas of photonics and biomedical optics.