Patent Publication Number: US-2022238246-A1

Title: Fiber optical tweezers

Description:
RELATED APPLICATIONS 
     This patent application claims the benefit under 35 U.S.C. § 119(e) of U.S. Provisional Patent App. No. 63/141,839, filed Jan. 26, 2021, entitled “FIBER OPTIC TWEEZERS,” incorporated herein by reference in entirety. 
    
    
     STATEMENT OF FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT 
     This invention was made in whole or in part with government support under grant No. CBET-1403257 awarded by the National Science Foundation. The government has certain rights in the invention. 
    
    
     BACKGROUND 
     Optical trapping of dielectric particles by a single-beam gradient force has been attributed to Arthur Ashkin, who received the Nobel Prize in physics for this work (2018). Generally, this work relates to the detection of optical scattering and gradient forces on micron sized particles. Subsequent developments employ a laser or similar optical source to manipulate microscopic particles based on attractive and/or repulsive forces generated between the particle and the surrounding medium based on the optical source. 
     SUMMARY 
     A fiber optical based particle manipulation system employs one or more optical fibers for emanating a refracted optical manipulation signal directed at a target particle for fixing or manipulating the particle for examination, research and manufacturing. A target particle may be a living cell or inanimate sample or compound of matter. An alignment linkage controls optical fibers carrying the manipulation signal for focusing one or more manipulation signals on the target particle. Manipulated particles occupy a fluid medium of either liquid or gas, and are responsive to the manipulation signal based on both photon bombardment and temperature differential from photon contact. 
     The temperature differential is based on surface properties of the target particle, as smooth particles tend to exhibit a greater thermal differential for stronger displacement forces driving or affecting the target particle. Research and production facilities benefit from an ability to maintain or move a particle under microscopic observation for response of the target particle to external stimuli, such as biological, chemical or magnetic influences for accurately capturing particle response. 
     A pair of optical fibers engaged in an alignment linkage may be used to form optical tweezers (OTs), which are important tools widely applied in biology, material science and physics. Miniaturization and integration are desirable trends for the development of OTs. Miniature OTs with an integrated component package can be implemented in systems such as integrated analytical devices, and are beneficial in transitioning optical trapping technology from the research lab to practical applications. 
     Despite the importance, miniaturization and integration of conventional optical tweezers has met with shortcomings. Conventional OTs are built on a microscope platform with a strongly focused laser beam and an objective lens with a high numerical aperture (NA), the latter of which is required for both creating a trap and detecting the trapped particle position. Therefore, traditional OTs inherit the limitations of the high NA objective and free-space optics, including the bulky size, short working distance, integration complexity and susceptibility to environmental fluctuations. 
     Accordingly, configurations herein substantially overcome the shortcomings of conventional particle manipulation practices by providing a fiber optical particle manipulation device, including one or more optical fibers emanating from an optical source, each having a finished end on the optical fiber distal from the optical source. An alignment linkage is engaged with the optical fiber for manipulating the finished end, such as a pivotal, robotic or manually disposed control attached near the finished end for directing the emanated manipulation signal. A signal generator in the optical source transmits the manipulation signal to the distal, finished end. The finished end is adapted to direct the manipulation signal towards a particle for movement or fixation, and may emanate from 1 or more optical fibers; 2 in the case of a particle trap. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The foregoing and other objects, features and advantages of the invention will be apparent from the following description of particular embodiments of the invention, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention. 
         FIG. 1  is a context view of an example configuration of the fiber optical particle manipulation device (optical tweezers); 
         FIG. 2  shows the optical fibers in the device of  FIG. 1 ; 
         FIG. 3  is a schematic diagram of optical fibers as in  FIG. 2 ; 
         FIG. 4  shows particle manipulation using optical fibers as in  FIG. 3  based on a thermal differential; 
         FIG. 5  shows particle manipulation using optical fibers as in  FIG. 3  based on identification of surface features; and 
         FIG. 6  shows a system for rendering particle manipulation feedback with optical fibers as in  FIGS. 1-5 . 
     
    
    
     DETAILED DESCRIPTION 
     Optical tweezers have been employed to apply and measure forces to micro/nanoscale particles. For example, optical tweezers are commonly used in biological and physical research, such as the study of the motion of individual motor proteins, mechanical properties of polymers and biopolymers, tests of the fundamental nature of gravity, and attractive forces between like-charged particles. 
     Conventional, commercialized optical tweezers are based on objective lenses and microscopes. They are expensive, bulky, and difficult to be integrated. In addition, users are required to undergo substantial training to operate optical tweezers. 
     The modular fiber optical tweezers claimed herein are designed to solve the abovementioned problems and have demand potential in industry, research labs, and education. Modular FOTs are 1) miniaturized and portable, 2) easy-to-use, 3) economic and readily operable without extensive training. 
     Conventional approaches to OT and particle manipulation suffer from shortcomings that arise from the intrinsic limitations of objective lenses, such as bulkiness, short working distances, and integration difficulty with microscopes, such as substantial mass and poor flexibility. It is challenging for traditional OTs to be operated outside a lab environment due to the free space optics, which significantly limit their applications. In addition, the operation of commercially available traditional optical tweezers requires an air cushion table and a full laboratory environment. 
     Configurations herein present a maintenance-free, all-fiber modular optical tweezers (AFMOTs) system that can reliably create an optical trap that is freely movable on a sample substrate. It includes two inclined optical fibers pre-aligned and permanently fixed to a centimeter-scale common base, board or mounting surface, where the optical trap is located at the tips of the two fibers, well below the base. Such a modular design eliminates the need of the fiber alignment maintenance and free-space optics, while the mobility of the trap is reserved with the performance reliability. Compared with conventional counter-propagating fiber trapping systems, which may also be a modular system, the optical trap created by AFMOTs can be freely moved inside the medium, pick up a particle lying on a substrate or suspended in a gaseous or liquid medium, and move the particle around on the substrate. In addition to the system integration with devices such as so-called lab-on-a-chip devices and microscopes, the combination of trap mobility and reliability bestows on the AFMOTs great potential in finding applications that are challenging for other fiber optical tweezers. For example, AFMOTs can be used in the biomechanical investigation of cells in their original locations in the cultured media or tissues, as well as long-period applications such as the cell studies during its growth and division. As a demonstration for the applications, AFMOTs may be used as a functional tool to “probe” the mechanical properties of cells in their original locations in the cultured medium. 
       FIG. 1  is a context view of an example configuration of the fiber optical particle manipulation device (optical tweezers). Referring to  FIG. 1 , A fiber optical particle manipulation device  100  includes one or more optical fibers  110 - 1  . . .  110 - 2  ( 110  generally), each having a corresponding actuator  112 - 1  . . .  112 - 2  ( 112  generally) emanating from an optical source, and a finished end  114  on the optical fiber distal from the optical source. A base  102  has alignment linkage  120  to engage each optical fiber  110  via the respective actuator  112  or support for manipulating the finished end  114 . For example, in a fixed trap arrangement, the alignment linkage  20  maintains the relative fixed position between opposed fibers  110 . A signal generator in the optical source, discussed further below, transmits a manipulation signal, or optical signal, to the finished end for directing the manipulation signal towards a particle. 
     In the example of  FIG. 1 , the modular FOTs is a miniaturized system block with the total length around one inch, width within one inch, and thickness within a quarter inch. A fixed alignment of the actuators  112  for particle trapping provides that it is user-friendly and easy to operate both in and outside a lab environment. By using different types of fibers in the same system design, the modular FOTs have various modalities that are suitable for trapping and manipulating particles with different sizes. 
     Specifically, 10˜100 um particles can be trapped by modular FOTs with cleaved fibers (fibers with a flat surface), 3˜20 um with lensed fibers, and 500 nm˜5 um using chemically etched tapered fibers. It is noted that the size range of the trappable particles (500 nm˜100 um) covers the sizes of many biological particles, such as bacteria, human cells, animal and plant cells, and yeast cells. 
       FIG. 2  shows the optical fibers in the device of  FIG. 1  based on detail block  200 . Referring to  FIGS. 1 and 2 , the particular configuration of  FIGS. 1 and 2 , two optical fibers  110  with an inclined angle are pre-aligned and permanently fixed on the base  102 . Thus, a 3D optical trap is created reliably and repeatably by a modular system with a footprint around 85×50×7 mm, The modular form factor therefore allows a straightforward mounting on or within the visual field of microscopes. The position of the pre formed optical trap  210  can be easily maneuvered by controlling the position of the base  102 . In addition to creating a trap, the AFMOTs enable the fiber-based particle position detection with a resolution of 2 nm. Alternatively, each actuator may be independently positioned. 
       FIG. 3  is a schematic diagram of optical fibers as in  FIG. 2 . Referring to  FIGS. 1-3 , the optical fiber  110  emits a manipulation signal based on a reflection or refraction effected by a treatment of the finished end. In the disclosed approach, the finished end  114  is at least one of cleaved, lensed, or etched for directing photons in the manipulation signal  150 - 1  . . .  150 - 2  ( 150  generally). In the example configuration, the optical fiber  110  is a cleaved single-mode fibers such as Corning® HI 1060. The finished end has an emanation surface  118  resulting in a predetermined refraction of emitted photons for defining a trap  116  based on an intersection of the multiple manipulation signals. Depending on the processing, polishing etc. of the finished end, the manipulation signal  150  may reflect or refract within the fiber, as shown in  FIG. 3  to aim or direct the emanated photons. 
     Compared with traditional OTs, AFMOTs with cleaved fibers are a better candidate to deform cells of tens of micrometers in size. The main reason is that forces generated by AFMOTs are distributed over a large illuminated area of cell surface within the spot size, which is around 10 μm. By comparison, the trap of traditional OTs is at a diffraction-limit spot on the order of sub-μm. In order to achieve the same total optical force to deform cells, the optical stress and required intensity by AFMOTs are much smaller than those by traditional OTs, although the optical power is similar. Therefore, the AFMOTs promise to be a safer tool for cells, because the photodamage is linearly dependent on the optical intensity. 
     When higher optical forces are required to deform cells, AFMOTs allow a larger increase in power before possible photodamage occurs. As another important advantage, AFMOTs can deform cells without the help of any force handle or surface treatment, while beads are attached to cells as force handles by most traditional OTs for cell mechanics study. No bead attachment is preferred because of the following reasons. First, the physical contact may introduce contamination and undesired physical or chemical modifications to cell surfaces. Secondly, optical forces applied onto beads give rise to concentrated forces applied on the cell membranes, which can develop nonlinear and non-uniform membrane stress distribution and in turn bring challenges to stress characterization induced by the bead-mediated point loading. 
     In addition, these concentrated forces are more likely to cause physical damage and disruption of cells than distributed forces. By comparison, the AFMOTs applies distributed forces directly on cell membranes without any physical contact or additional force handles, which can minimize the cell disruption and allow cells to deform more evenly. With all the aforementioned reasons, AFMOTs are a unique tool that is safer and more suitable for cell mechanics study than traditional OTs. Cells as small as 8 μm in diameter may be trapped/manipulated by the optical fibers  110 . A typical optical power is in the range of 30-250 mW. 
       FIG. 4  shows particle manipulation using optical fibers as in  FIG. 3  based on a thermal differential. In the disclosed approach, the particle exists in a fluid medium  160 , which may be either a liquid or gaseous medium. A signal generator  142  in the optical source for has circuitry and controls for transmitting a manipulation signal  144 , such as a laser, to the finished end  114 , such that the finished end is adapted to direct the manipulation signal towards a particle  140 . Based on the position of the optical fiber  110  by the actuator  112 , the signal generator  142  emits a manipulation signal  144 , which causes a photon emission pattern  148  or dispersion based on the emanation surface  118 . The manipulation signal  144  from the signal generator  142  energizes photons  145  in the manipulation signal for disposing the particle  140  in response to photonic bombardment from a dispersion pattern  148 . The dispersion pattern  148  results from the finishing of the emanation surface for dispersing the photons  145  in a wide or narrow angle to manipulate and trap the particle  140 . 
     When the medium  160  is gaseous, vacuum or near vacuum, the manipulation signal from the signal generator energizes photons  145  in the manipulation signal for disposing the particle  140  in response to a thermal differential adjacent the particle. As photons  145  strike or engage the particle, there is a tendency to generate heat from the impact. This heat causes a thermal differential resulting from increased thermal activity at an impact location T 1  on a target particle  140 , in contrast to the opposed side T 2 . A net thermal differential results from T 1 &gt;T 2 . 
       FIG. 5  shows particle manipulation using optical fibers as in  FIG. 3  based on identification of surface features. The signal generator  142  emanates the signal  144  for transport over the optical fiber  112  for refraction and dispersion based on the finishing of the emanation surface  118 . The manipulation signal  144  is directed towards the particle based on a surface characteristic of a target particle  140 ′, such that the target particle receives photons  145  in the manipulation signal  144 . Surface features such as peaks and roughness affect the temperature differential. A smooth side S 1  results in a greater temperature differential than the same photon engagement with a rough side R 1 , due to the tendency of the surface roughness, peaks, valleys and the like to absorb heat. Therefore, a temperature differential ΛS is greater than the rough side temperature differential ΛR, all other parameters being equal. The actuators  112  may be fixed, as in  FIG. 1 , or may responds to the alignment linkage, however the signal  144  and intensity is based on a morphology, or smooth/rough surface characteristics of the target particle  140 ′ For example, the alignment linkage may be configured to direct the manipulation signal  144  towards a smooth side Si of the target particle  140 ′, as the smooth side exhibits a greater thermal differential than a course side of the target particle. 
       FIG. 6  shows a system for rendering particle manipulation feedback with optical fibers as in  FIGS. 1-5 . As the manipulated particles  140 ,  140 ′ may span a considerable size range, from around 500 nm to 100 um, depending on the configuration of the finished end, visualization of the manipulated fibers is a feature. Referring to  FIGS. 1-6 , a feedback apparatus is configured for rendering particle information of a target particle for directing the manipulation signal  144  based on surface properties of the target particle  140 ,  140 ′. 
     Referring to  FIG. 6 , and continuing to refer to  FIGS. 1-5 , the particle manipulation method and device has particular advantages in a research environment for cell research, dust, airborne contaminants and other contexts where manipulation and/or fixation of a small particle or cell is utilized. A researcher  600  utilizes a magnification device  610 , such as a microscope, video camera/magnifier, or other capability for displaying/visualizing the particle  140  under observation onto a rendering device  612 . One or more actuators  112  defines the alignment linkage  120  for directing and focusing the manipulation signal  144  for disposing the particle  140  based on at least one of a temperature differential exhibited in the fluid medium and a surface feature of the target particle. In the expected configuration, the particle  140  is in a gaseous or vacuum space, and the actuators  112  may hold or steer/manipulate the particle in a particular direction. A visualized response  620  on the rendering screen or device is readily observable for guiding the actuators from an actuator control  121  or otherwise performing particle based research activities. 
     While the system and methods defined herein have been particularly shown and described with references to embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims.