Systems, devices, and methods for identifying, collecting, rearranging, and analyzing particles on the micrometer and nanometer scales.

Abstract

Systems and methods for manipulating nano- and micrometer-scale particles are described. The system generally includes an optical imaging system for acquiring an image of a particle sample, a processor for analyzing the image, identifying a particle of interest in the image, and determining a lateral position of the particle of interest within the particle sample, and a vacuum-based probe system including a movable probe and a vacuum pump configured to apply a vacuum to the probe. The processor provides instructions for moving the probe to the lateral position of the particle of interest and instructions for applying a vacuum to the probe such that the particle of interest is pulled away from the particle sample and held at the tip of the movable probe.

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims the benefit of priority of U.S. Provisional Patent Application No. 63 / 330,168, entitled "SYSTEMS, DEVICES AND METHODS FOR IDENTIFYING, COLLECTING, RELOCATING, AND ANAYZING MICROMETER - AND NANOMETER SCALE PARTICLES", filed on April 12, 2022, the content of which is incorporated herein by reference.

Background Art

[0002] As microanalysis technology has advanced and the state - of - the - art continues to miniaturize, there is an increasing need for particle manipulation devices with higher resolution and specific selectivity at the small micrometer (μm) to nanometer (nm) scale. The need for a device platform capable of spatially resolving μm - sized particles is evident in microanalysis fields such as nuclear forensic medicine and semiconductors, which require the identification and non - destructive relocation of micron - sized particles in order to enable sequential analysis through several complementary analysis platforms. Advanced manufacturing industries such as microelectronics will also benefit from μm - to - nm scale particle manipulation and analysis technologies to produce high - quality materials and remove contaminants.

[0003] Existing particle handling equipment suffers from various problems and shortcomings. For example, many existing particle handling systems have low resolution and are therefore unable to accurately detect, collect, and / or manipulate particles at the nano and micrometer scales. Existing particle handling systems also suffer from a lack of precision and selectivity, making it difficult or impossible to position and collect specific individual particles within a mixed sample. Particle contamination and / or damage is another problem faced by many existing systems. Relatively crude probes and / or collection techniques often lead to penetration or chipping of the particle surface, and if impure materials are used in the collection device, this can lead to sample contamination. Furthermore, many existing systems require extensive training and / or experience to operate, are incompatible with other systems (e.g., other analytical tools), and / or have excessively long sample collection times (e.g., several hours per particle).

[0004] Therefore, there is a need for new and improved particle handling systems, apparatus, and methods that solve some or all of the problems described above. [Overview of the project]

[0005] This summary of the invention is provided in a simplified form to introduce a selection of concepts that will be further described in the detailed description below. Neither this summary nor the aforementioned background art is intended to identify any important or essential aspects of the claimed subject matter. Furthermore, this summary is not intended to be used as an aid in determining the scope of the claimed subject matter.

[0006] In several embodiments, particle manipulation systems are disclosed and described. A particle manipulation system generally includes an optical imaging system configured to acquire an image of a mixed sample of particles, a processor configured to analyze the image, identify a target particle in the image, and determine the lateral position of the target particle within the mixed sample of particles, and a vacuum-based probe system. The vacuum-based probe system includes a movable probe and a vacuum pump configured to apply vacuum to the probe. During operation, the processor commands the vacuum-based probe system to move the movable probe to the lateral position of the target particle, and to start the vacuum pump so that the target particle is pulled away from the mixed sample of particles and held at the tip of the movable probe, thereby applying vacuum to the probe. In some embodiments, the probe may subsequently reposition the target particle to a different location, such as separating it from the mixed sample of particles. In some embodiments, the particle manipulation system is adapted for use with nanoscale and micrometer-scale particles.

[0007] In some embodiments, methods for manipulating nanoscale and micrometer-scale particles are disclosed and described. The method generally comprises the steps of obtaining a magnified image of a mixed particle sample, the mixed particle sample comprising a plurality of particles having sizes ranging from about 0.01 to about 1,000 micrometers; analyzing the magnified image to identify a target particle; determining the lateral position of the target particle within the mixed particle sample; moving a vacuum-based probe to the lateral position of the target particle; and applying vacuum to the vacuum-based probe, thereby separating the target from the mixed particle sample and holding the target particle at the tip of the probe. In some embodiments, the method further comprises the steps of moving the vacuum-based probe, with the target particle held at its tip, to a lateral position on a particle collection tray; and stopping the vacuum so that the target particle is released from the tip of the vacuum-based probe and deposited on the particle collection tray.

[0008] These and other aspects of the technology described herein will become apparent upon consideration of the detailed description and drawings herein. However, it should be understood that the scope of the claimed subject matter will be determined by the claims as published, and not by whether a given subject matter addresses any or all of the problems pointed out in the background art or whether it includes features or aspects described in the abstract of the invention.

[0009] Non-limiting and non-exclusive embodiments of the disclosed technology, including preferred embodiments, are described with reference to the following figures, and unless otherwise specified, similar reference numbers throughout the various figures refer to the same parts. [Brief explanation of the drawing]

[0010] [Figure 1] This figure illustrates a method for identifying, collecting, and rearranging particles according to various embodiments described herein. [Figure 2] This is a schematic diagram of a system for identifying, collecting, and relocating particles, according to various embodiments described herein. [Figure 3] This figure shows a method for forming a probe suitable for use in the methods and systems described herein, according to various embodiments described herein. [Figure 4] This is a flowchart illustrating a method for identifying, collecting, and rearranging particles according to various embodiments described herein. [Figure 5A] This is a flowchart illustrating a method for identifying, collecting, and rearranging particles according to various embodiments described herein. [Figure 5B] This is a flowchart illustrating a method for identifying, collecting, and rearranging particles according to various embodiments described herein. [Modes for carrying out the invention]

[0011] Embodiments form part of this specification and are described more fully below with reference to the accompanying drawings illustrating specific exemplary embodiments. These embodiments are disclosed in sufficient detail so that those skilled in the art can practice the invention. However, embodiments can be implemented in many different forms and should not be construed as being limited to the embodiments described herein. The following detailed description should therefore not be construed as restrictive.

[0012] This specification describes various embodiments of particle manipulation systems configured to identify, position, collect, and reposition one or more particles within a sample of particles with high precision, so that the system can manipulate particles on the nanoscale and micrometer scale. The system design is also designed so that particles on the nanoscale and micrometer scale can be manipulated without damaging, destroying, and / or contaminating the particles. The system may be designed to include various components configured to identify one or more particles of interest within a sample of particles, determine the lateral position of one or more particles of interest within a sample of particles of interest, move a probe to one of the precise lateral positions in the sample of one or more particles of interest, apply a vacuum to the probe, thereby pulling the particle away from the sample and holding it at the tip of the probe, and then move the probe to reposition the particle. Various embodiments of related methods for identifying and manipulating particles of interest in general in accordance with the above description are also described herein. As used herein, the term, particle, may mean an individual particle or a particle that is part of a cluster of two or more particles. Accordingly, the particle handling systems and methods described herein can be used to identify, locate, collect, and rearrange single particles or particle clusters within a particle sample.

[0013] Referring to Figure 1, a description of a general method 100 for manipulating particles according to various embodiments described herein is provided. The method generally comprises steps 110 to 140, where step 110 comprises providing a mixed sample of particles, step 120 comprises obtaining an image of the mixed sample of particles, step 130 comprises analyzing the image to identify, for example, the precise location of one or more particles in the mixed sample of particles, and step 140 comprises collecting the target particles from the mixed sample of particles (which may be part of a cluster of particles) and optionally rearranging the target particles.

[0014] In step 110, a mixed particle sample 111 is provided. When used herein, the phrase “mixed particle sample” is intended to convey that the particles contained in the sample do not all need to be identical. For example, a mixed particle sample may contain particles of different sizes, shapes, and / or types of materials. However, it should be understood that the systems and methods described herein can also be used for samples that are similar or identical in several respects, such as having relatively uniform shapes and sizes, the same type of material, etc. A mixed particle sample may also contain any number of particles, including a single particle. In some embodiments, at least some of the particles contained in the mixed particle sample 111 have a size in the range of 0.01 to 1,000 micrometers. A mixed particle sample may also contain particles having sizes outside this range, but such particles would generally not be the particles of interest. Particles considered to have a size in the range of 0.01 to 1,000 micrometers should only indicate a single dimension within the stated size range. The dimensions of the particle used to determine its size may include any dimensions (e.g., length, width, thickness, diameter, etc.). A mixed sample or particles may include separated particles, clusters of particles, or combinations thereof.

[0015] The particle sample provided in step 110 may be a dry sample of particles, or it may include particles that are completely or partially immersed in liquid. A dry sample generally includes one or more particles placed on a substrate, with no (or significant) liquid on the substrate so that the particles are not partially or completely immersed. A wet sample may include a substrate that is completely covered in liquid, with particles partially or completely immersed in it, or a substrate with a large amount of liquid on its surface, but not completely covering the substrate, with one or more particles partially or completely immersed. A wet sample may therefore include some dry areas on the substrate surface, on which dry particles may be present.

[0016] As shown in Figure 1, the particle mixture sample 111 contains multiple particles 111a arranged in various positions. While Figure 1 shows particles 111a that are all spherical but of varying sizes, it should be understood that sample 111 may contain multiple particles that are more uniform in size and / or have different shapes. All the particles shown in Figure 1 may be of the same material type or may be made from different materials.

[0017] In step 120, an image 121 of the particle sample 111 is acquired, for example, by using an optical microscope. In some embodiments, dark-field imaging may be used to acquire the image 121 of the particle sample 111, but it should be understood that other imaging techniques can be used as long as an image showing the location of most or all of the particles 111a in the particle sample 111 is provided. In some embodiments, the image may also show the size and shape of the particles 111a.

[0018] In step 130, image analysis is performed on image 121 to provide the analyzed image 131. Any suitable image analysis technique can be used, as long as it is capable of identifying one or more particles in image 121 that satisfy one or more selected identification criteria. As shown in Figure 1, the analyzed image 131 contains various particles 131a that have been identified as target particles based on the image analysis performed determining that these particles satisfy the selected identification criteria. As part of the image analysis step 130, the exact lateral position of each particle 131a is determined and / or recorded. As used herein, the term “lateral” means substantially in the horizontal plane and includes both the x and y directions in the horizontal plane.

[0019] In step 140, the vacuum probe 141 is moved to a lateral position of the target particle 131a so that the probe 141 is precisely positioned on the target particle 131a. The vacuum probe 141 and the target particle 131a are located within the same lateral position (i.e., x and y positions), but there may be a separation distance in the z direction between the tip of the vacuum probe 141 and the top of the target particle 131a. This separation distance in the z direction may be relatively small so that the target particle 131a is pulled up from the particle sample 111 by applying vacuum to the probe 141. The vacuum probe 141 may also be movable in the z direction to adjust the separation distance between the tip of the probe 141 and the target particle 131a. Once the probe 141 is moved to the same lateral position as the target particle 131a (and optionally moved in the z direction to adjust the separation distance between the tip of the probe 141 and the top of the particle 131a), a vacuum is then applied up to the probe 141 so that the target particle 131a is lifted from the sample 111 and held at the tip of the probe 141.

[0020] Once the particle 131a is fixed to the probe 141 in this manner, the probe 141 may be moved to reposition the target particle 131a. In some embodiments, the probe 141 is moved to a particle collection tray 142 separate from the sample 111. A lateral position (i.e., x and y coordinates) on the collection tray 142 may be selected, and once the probe 141 is moved to the new lateral position, the particle 131a is released from the probe 141, for example by stopping the vacuum flow through the probe 141, thus resulting in the deposition of the particle 131a at a precise location on the collection tray 142. In some embodiments, the probe 141 may include a vent that can be opened when the particle 131a is released. Opening the vent of the probe 141 eliminates the suction force applied by the vacuum without the need to turn off the vacuum. Other methods for releasing particles from the tip of the probe can also be used and will be discussed in more detail below. As previously discussed and described in more detail below, the vertical (i.e., z-direction) movement of the probe 141 toward or away from the particle can also be incorporated into various parts of the method.

[0021] In an alternative embodiment, the probe 141 to which the particle 131a is fixed remains substantially stationary after capture, and the collection tray 142 is moved below the probe 141 so that the captured particle 131a can be deposited on the collection tray 142. In such embodiments, the sample 111 remains in place and the collection tray 142 can be moved to a position above the sample 111 but below the probe 141, or the sample 111 can be moved laterally and the collection tray 142 can be moved laterally into the space freed up by the lateral movement of the sample 111. In any case, the lateral movement of the collection tray 142 is very precise so that the collection tray 142 is positioned below the probe 141 so that the exact position on the collection tray 142 where the captured particle 131a will be deposited is located below the probe 141.

[0022] The method of depositing the target particle 131a onto the collection tray 142 may be such that the position / orientation of the target particle 131a does not substantially change from its position on the sample 111. For example, if the target particle 131a has a generally triangular shape with the corners of the triangle facing south, northwest, and northeast, the particle 131a is captured by the probe 141 at this position and deposited in substantially the same orientation. In other embodiments, the orientation of the particle can be changed as part of the collection and repositioning systems and methods described herein. In one example, the probe 141 may be rotatable about its longitudinal axis so as to be able to adjust the orientation of the particle by 360 degrees.

[0023] As described above, the ability to accurately determine the position of the target particle, the ability to move the probe to an accurate position, and the ability to move the collected target particle to an accurate position on the collection tray provide a highly improved and highly desirable micro- and nanometer-scale particle manipulation system. In some embodiments, the accuracy of the movement of the probe, sample tray, and / or collection tray is aided by the type of system used to move the probe, sample tray, and / or collection tray. For example, the selection of a stepper motor or piezoelectric system can affect the accuracy with which the various components of the system can be moved.

[0024] The spatial accuracy with which the collected particles can be placed, for example, on a particle collection tray, enables the systems and methods described herein to be used for various purposes. In some embodiments, once the particles are accurately placed on the collection tray, additional analysis of each individual particle can be performed. The systems and methods also enable the creation of an accurate pattern of repositioned particles, which can be useful, for example, in nanofabrication.

[0025] The above considerations of FIG. 1 provide a general description and introduction of the systems and methods for particle manipulation disclosed herein. Further details regarding both the system and the method are provided below.

[0026] Referring now to Figure 2, a system 200 configured to perform various embodiments of the method described in Figure 1 is shown. The system 200 generally includes an optical imaging system 210 (including an optical microscope 211, a light source 212, and a camera 213), a probe 220 (including a probe moving system 221), a vacuum system 230 (including a vacuum pump 231, a valve 232, and optionally a flow meter 233), a processor 240, and a sample moving system 250 (on which a particle sample 251 may be placed).

[0027] Referring to the optical imaging system 210, the optical imaging system 210 generally includes at least an optical microscope 211, a light source 212, and a camera 213. In some embodiments, as commonly shown in Figure 2, the longitudinal axis of the optical microscope 211 is oriented substantially perpendicular to the plate or tray on which the particle sample is placed, while in other embodiments, the longitudinal axis of the optical microscope 211 may be positioned at an angle between 0 and 90 degrees relative to the plate or tray. The optical microscope 211 and the camera 213 are communicatively coupled so that images acquired by the microscope 211 are recorded by the camera 213. Any suitable type of microscope 211 can be used, but in some embodiments, the microscope 211 is a microscope configured to acquire high-resolution images of nano and micrometer-scale particles in particular. In certain embodiments, the optical microscope includes an objective lens with a moderate numerical aperture and a long working distance (about 1 cm). By using an objective lens with a suitable long working distance, sufficient space is provided for both the illumination of the sample 251 and the introduction of the probe 220 onto the surface of the sample 251. The light source 212 can be any suitable light source capable of illuminating the sample 251, such as a broadband light source. In some embodiments, the light source 212 is capable of directing light onto the sample 251 at a high angle of incidence. The light source 212 may also include an achromatic lens.

[0028] In some embodiments, the optical imaging system 210 is configured for dark-field optical microscopy (also referred to as dark-field imaging or dark-field illumination). Dark-field optical microscopy is well suited for imaging particles containing fire-resistant materials. Generally speaking, a light source 212 with a high angle of incidence irradiates light onto the fire-resistant material, causing some of the light to be refracted by the fire-resistant material. The optical microscope 211 then captures this refracted light as a means of imaging the particles. While the optical imaging system 210 may be configured for dark-field optical microscopy, the specific types of optical imaging performed by the optical imaging system 210 are not limited. Other optical imaging methods that can be performed by the optical imaging system 210 include, but are not limited to, bright-field, phase-contrast, fluorescence, and Raman imaging. Depending on the optical imaging method used, the particles may be fire-resistant or non-fire-resistant. In one non-limiting example, bright-field optical imaging can be used if the sample contains non-fire-resistant particles.

[0029] The optical imaging system 210 is communicatively coupled to the processor 240 so that an image of the mixed particle sample 251, acquired by the optical imaging system 210 and recorded by the camera 213, can be transmitted to the processor 240 for processing and analysis. In particular, the processor 240 is programmed to receive the optical image, analyze the optical image (either automatically or by user input) to identify target particles, and determine and / or record the precise lateral position (i.e., x and y coordinates) of the target particles. This information can then be used in combination with the probe 220 and probe movement system 221 to collect the target particles, as will be discussed in more detail below. The processor 240 may be part of a computing device (not shown in Figure 2), such as a CPU, which may further include, for example, a display, a server, and / or hardware memory for storing software and computer instructions, or may be communicatively and / or operationally connected to these. The processor 240 may be, for example, a microprocessor. The processor 240 may store and retrieve data and applications in memory, including applications that process information and send commands / signals according to any of the methods disclosed herein. The processor 240 may also be configured to (i) display objects, applications, data, etc., on an interface / display, and / or (ii) receive input through the interface / display. The processor 240 may also be connected to a transceiver.

[0030] System 200 includes a probe 220 (and a probe movement system 221) and a vacuum pump system 230 (including a vacuum pump 231, a valve 232, and optionally a flow meter 233). In some embodiments, the longitudinal axis of the probe 220 is oriented substantially perpendicular to the plate or tray on which the particle sample is placed, while in other embodiments (and as commonly shown in Figure 2), the longitudinal axis of the probe 220 may be positioned at an angle between 0 and 90 degrees with respect to the plate or tray. The vacuum pump system 230 is in fluid communication with the probe 220 such that when the vacuum pump 231 is started and the valve 232 is opened, air is drawn to the tip of the probe 220 and drawn upward through the body of the probe 220, lifting the target particles away from the sample 251 and providing a suction force at the tip of the probe 220 that is capable of holding the particles at the tip of the probe 220 as long as the suction force is maintained. The vacuum pump 231, the valve 232, or both, are communicatively coupled to the processor 240 so that the processor can control the operation of the vacuum pump (i.e., turning the vacuum pump on or off) and / or the operation of the valve (i.e., opening or closing the valve).

[0031] An optional flowmeter 233 typically monitors the airflow through it to help determine when particles have been drawn up relative to the tip of the probe 220. For example, if the flowmeter 233 detects a significant drop in airflow, this generally indicates that particles have blocked the tip of the probe 220, and therefore the probe 220 has successfully collected particles from the sample 251. By communicatively coupling the flowmeter 233 to the processor 240, the processor 240 is provided with information indicating that the target particles have been collected by the probe 220. This can then be used to send further commands to the probe 220, or more specifically, to a probe movement system 221 configured to move the probe 220. For example, if the processor 240 receives information from the flowmeter 233 indicating that particles are being collected at the tip of the probe 220, the processor 240 may send a command to the probe moving system 221 instructing it to move the probe 220 to a position on the target particle collection tray 260. The processor 240 may provide the probe moving system 221 with a precise lateral position on the target particle collection tray 260 so that the particles are precisely positioned on the target particle collection tray 260.

[0032] While the flowmeter 233 is described above as being used to determine when a particle is captured by the probe, it should be understood that other means of determining the capture of the target particle can also be used. For example, an optical sensor may be used alone or in combination with the flowmeter discussed above to determine when the target particle is held at the tip of the probe. Similarly, a pressure sensor may be used as part of determining when the target particle is fixed at the tip of the probe.

[0033] System 200 further includes a sample moving system 250 on which a particle sample 251 is placed. The sample moving system 250 is capable of positioning the sample 251 under the microscope 211 so that an optical image of the sample 251 can be acquired. The specific type of moving system used for both the sample moving system 250 and the probe moving system 221 is not limited. As shown in Figure 2, a triaxial piezoelectric system is provided for both the sample moving system 250 and the probe moving system 221. Both moving systems 221, 250 are communicably coupled to a processor 240 so that the processor can send commands to the systems 221, 250 to move the sample 251 and / or probe 220.

[0034] While System 200 has been discussed above as using a probe moving system 221 to move the probe 220 to a lateral position on a target particle placed on a stationary sample 251, it should be understood that if the system includes a sample moving system 250, System 200 and the related methods described herein can also be used by keeping the probe 220 stationary and moving the sample 251 via the sample moving system 250, thereby aligning the target particle beneath the stationary probe 220. In other words, the sample 251 may be moved in the x and y directions to position the target particle beneath the stationary probe 220, at which point the probe 220 may be actuated (e.g., by initiating a vacuum) to pull the target particle, which has been moved beneath the probe 220, away from the sample 251.

[0035] The processor 240, which connects various components of system 200 in a communicative manner, is generally any type of processor capable of receiving information and / or data, processing information / data, and providing instructions (possibly instructions based on the information / data processed therein) to the components of system 200. In some embodiments, the processor 240 is or includes a central processing unit (CPU). In some embodiments, the processor 240 may include or be part of a personal computer (PC) or other similar device capable of performing the processor functions previously described. The processor 240 is programmable so that the functions previously described, and other functions not specifically described herein, can be performed by the processor 240. This helps to highly customize the entire system 200 based on the various instructions loaded into the processor 240 (e.g., via software).

[0036] Although not shown in Figure 2, some or all of System 200 may be built on a vibration-isolating table or pad to minimize the effects of vibration on delicate micro or nanoscale manipulators.

[0037] Referring here to Figure 3, further details of the probe 220 are provided. The probe 220 may generally have a needle-like configuration having a hollow passage 221 extending through the probe 220 and terminating at a distal tip 222 having an opening 223. The opening 223 has a diameter d1 that is generally smaller than the diameter d2 of the main body of the probe 220, so that the probe 220 tapers overall towards the distal tip 222 of the probe 220. Although not shown in Figure 3, the tip of the probe 220 may be chamfered instead.

[0038] As discussed in more detail with respect to Figure 2, the vacuum pump system 230 is in fluid communication with the probe 220 such that air is drawn into the probe through the opening 223 at the tip 222 and into the main body of the probe 220, thereby creating an attractive force at the tip 222. If the tip 222 of the probe 220 is positioned close enough to the target particles, the target particles will be drawn to and held at the tip 222 of the probe 220, as long as the vacuum pump system 230 continues to draw air onto, into, and through the probe 220. Generally speaking, to ensure that particles enter the probe 220 through the opening 223, the diameter d1 of the opening 223 should be less than or equal to the size of the smallest particles collected by the probe. In some embodiments, d1 is in the range of 0.01 to 1000 micrometers, for example, 0.1 to 10 μm. In some embodiments, d1 does not exceed 1 μm.

[0039] The material of the probe 220 is generally not limited as long as a needle-shaped probe of the desired dimensions can be fabricated from the selected material. That said, in some embodiments where particle contamination is to be avoided, the probe material may be selected from materials that will not contaminate particles upon contact. In some embodiments, this generally requires a metal-free material. In some embodiments, glass-type materials are preferred for non-contamination applications. In some embodiments, quartz is a preferred material for probes due to its non-contamination properties. Other materials that may be used for probes include, but are not limited to, borosilicate glass, aluminosilicate glass, or plastics.

[0040] Figure 3 also provides an explanation of a method for forming the probe 220. In some embodiments, the probe 220 is formed using laser-assisted pipette pulling. As indicated by the arrows in Figure 3, this generally involves pulling the tube of probe material in opposite directions after and / or while heating the middle portion of the tube. The opposing pulling force will ultimately result in the separation of portions of the probe material, forming tapered tips at each point of separation. Probes formed in this manner may be characterized via optical microscopy, transmission electron microscopy (TEM), and / or electrochemistry, depending on the expected size of the probe, to determine the final dimensions of the formed probe (e.g., diameter of the tip opening). Parameters used in the manufacturing process (e.g., initial capillary dimensions, laser power, irradiation pattern, heating time, pulling strength, time delay, etc.) may be systematically modified to express suitable conditions for producing probes with desired tip opening dimensions and / or probe shapes (e.g., between 100 nm and 10 μm).

[0041] As mentioned above, a general design requirement is that the diameter of the probe tip opening is smaller than the target particles. In some embodiments, the correlation between the tip opening size and the target particles that can be collected using a particular tip opening size must be considered. For example, a relatively small tip opening (e.g., 100 nm) may fail to collect some larger particles (e.g., 100 μm) due to insufficient suction through the small tip size. In some embodiments, the tip opening size should not be less than one-tenth the size of the particles to be collected.

[0042] Given the potential limitations in collecting particles of a specific size using probes with relatively small tip apertures, an alternative embodiment of the system 200 shown in Figure 2 may include multiple probes 220, each with different tip aperture diameters. This configuration allows the system to collect a wider range of particles from a sample. The system 200 may be configured to automatically consider the size of the particles to be collected (which may be determined, for example, during image analysis) and use the appropriate probe for collection. For example, the system may include a first probe with a tip aperture diameter of 0.01 μm and a second probe with a tip aperture diameter of 1 μm. If the size of the particles to be collected is 5 μm, the system 200 (via the processor 240) recognizes that the first probe is unlikely to generate sufficient suction to collect particles of this size, and therefore instructs the second probe to collect the target particles. Similarly, if the size of the particles to be collected is 0.1 μm, the system 200 (via the processor 240) recognizes that it should send the first probe to collect particles of this size to avoid the second probe being drawn into the body of the second probe through its 1 μm tip opening. The second probe, having a larger diameter opening, may also be suitable for collecting clusters of particles in scenarios where the clusters of particles are well-adhered to each other, such that the attractive force applied to the cluster by the second probe for collection purposes does not result in one or more particles being separated from the cluster of target.

[0043] Although not shown in Figure 3, alternative embodiments of probe 220 may include additional structures and / or materials at the probe tip to create better contact between the probe tip and the target particle. Such additives may be particularly useful for target particles having irregular shapes. In some embodiments, the probe tip may include a flexible mask or membrane that can conform to the shape of the particle to create a better suction seal between the tip and the particle. When such tip additives are used, care must be taken to ensure that the material of the tip additive is sufficiently flexible so as not to damage the particle when the additive comes into contact with the target particle. Care must also be taken to ensure that the material of the additive is not contaminated.

[0044] A problem may also arise in which particles “adhere” to the tip of the probe 220. In such cases, the particles may not be released from the probe 200 even when the vacuum suction is stopped. Particle “adhesion” may occur, for example, due to electrostatic effects. Therefore, in some embodiments, the probe 220 is further modified or treated to prevent particle “adhesion.” In some embodiments, chemical modification of the probe 220 is performed, such as chemical modification of the probe 220 through treatment with alkoxysilanes having different functional groups to change the hydrophobicity and / or polarity of the probe 220 surface. In other embodiments, modifications of the probe to prevent particle “adhesion” include coating the probe surface with metal to allow any static electricity to dissipate. In some embodiments, a silver film manufactured by the Thorens process may be used.

[0045] While the embodiments described previously generally rely on stopping the attractive force generated by applying a vacuum to the probe to release particles from the probe, it should be understood that other methods of releasing particles can be used in conjunction with, or instead of, stopping the attractive force. For example, physical movement of the probe (e.g., changing the Z position up and down relatively quickly and continuously) can be used to release particles. Alternatively, an adhesive / attractive substrate can be used, where the adhesive attractive force between the particle and the adhesive / attractive substrate can overcome the attractive and / or adhesive / attractive force between the particle and the tip of the probe. In yet another example, static force can be used to separate the particle from the tip of the probe. In yet another example, the vacuum to the probe can be stopped, and then air can be blown down through the probe (i.e., towards the tip of the probe) to push the particle away from the tip of the probe.

[0046] As stated above, the particles that can be identified, collected, and rearranged by the systems and methods described herein are not generally limited, as long as the particles can be imaged and are of a size appropriate for the specific system and method used. In some embodiments, the systems and methods described herein are particularly well suited to handling (e.g., collecting and rearranging) particles having particle sizes in the range of 0.01 to 1,000 micrometers. The material of the particles is also not generally limited, but in some embodiments, the systems and methods described herein are particularly well suited to handling particles made from refractory materials. Non-limiting materials include SiO2, Al2O3, and SiC. The systems and methods described herein can also be applied to other materials such as metal oxides, metals, or microplastics. The general shape of the particles is also not limited. Particles may have regular shapes such as spheres or cubes, or they may have irregular shapes. While the shape of the particles may have some influence on the probe's ability to collect target particles, the systems and methods described herein are assumed to be capable of collecting particles of any shape through a probe with appropriately sized tip opening diameters and / or tip attachments, via the use of an appropriate amount of suction force.

[0047] As previously discussed, the particles handled by the systems and methods described herein are generally placed on a substrate to form a mixed sample of particles. The material of the substrate used to support the particles is generally not limited. Similarly, the material of the tray or substrate on which the particles are placed after being identified and removed from the mixed sample of particles is also not limited.

[0048] Finite element simulations have been performed to estimate the flow rates through probes necessary to collect spherical and cubic particles. These flow rates are estimated to be around 10–100 μL / min, making contact detection via airflow monitoring (discussed in more detail herein) a feasible strategy. Furthermore, based on the similarity of flow rates determined to be successful in collecting spherical and cubic particles, it is predicted that the geometric shape of the particles will not significantly affect the ability of the methods and systems described herein to successfully collect particles of various shapes.

[0049] Referring to Figure 4, a flowchart is provided showing a method 400 for operating the system described in Figure 2 so that target particles are identified, positioned, collected, and repositioned. The method 400 shown in Figure 4 generally includes the steps of: acquiring a magnified image 410 of a sample of particles; analyzing the magnified image 420 to identify target particles; determining the lateral position of the target particles within the sample of particles 430; moving a vacuum-based probe to the lateral position of the target particles 440; and applying vacuum to the vacuum-based probe, thereby pulling the target away from the particle sample and holding the target particles at the tip of the probe 450. Although not shown in Figure 4, the method 400 may further include the steps of moving the vacuum-based probe to a new position after the target particles have been pulled away from the sample and held at the tip of the probe, and releasing the vacuum, thereby depositing the target particles at the new position by causing them to fall from the tip of the probe.

[0050] In step 410, a magnified image of the particle sample is acquired. As discussed in more detail above, the magnified image may be acquired, for example, by an optical microscope and using dark-field imaging. Once the image is acquired, it may be sent to a processor for image analysis in step 420. In some embodiments, the particle sample from which the magnified image is acquired may consist of multiple particles that may have varying sizes, shapes, and / or types of materials. In some embodiments, the size of the particles in the sample is in the range of 0.01 to 1,000 micrometers.

[0051] Regarding step 420, an analysis of the magnified image is performed to identify one or more target particles in the image. Such analyses are typically performed by a processor configured to receive the image acquired in step 410. The processor may be equipped to perform any suitable type of analysis using any suitable software platform, as long as the analysis performed can measure one or more criteria of particles in the sample and the measured criteria can be used to identify target particles. Identifying target particles may generally involve identifying those particles that satisfy one or more selection criteria. Any selection criteria or combination of selection criteria may be used, and the processor may be programmed to use various types of selection criteria to make the entire system more adaptable to various types of samples. In one basic example, the selection criterion is particle size. In this example, the image is analyzed in step 420 to determine the size of all particles in the sample of particles. The processor then applies a size selection criterion (e.g., only particles with a size in the range of 100 to 500 micrometers are target particles), and particles that satisfy this selection criterion are considered target particles.

[0052] In step 430, the processor determines or records the precise location of each target particle within the sample. Generally speaking, the lateral position of each particle (i.e., the x and y coordinates within the sample) is determined and recorded. Due to the inclusion of nano and micrometer scales, the lateral coordinates are determined with great precision to ensure that the probe can collect the specific target particle. If the x and y coordinates are not determined with sufficient precision, this poses a risk that the probe may not be able to collect the target particle (for example, if the probe is positioned in an empty space near the target particle) or that the probe may collect the wrong particle (for example, if the probe is positioned on a particle adjacent to the target particle).

[0053] In step 440, the vacuum-based probe is moved to a lateral position of the first target particle identified during the analysis step 420. The probe can be moved precisely to coincide with the exact position of the first target particle determined in step 430. Any suitable means for moving the probe can be used, but in some embodiments, a triaxial piezoelectric system is used. The triaxial piezoelectric system is capable of moving the probe to precise positions in the x and y directions, and it is also possible to move the probe in the z direction, as will be discussed in more detail herein.

[0054] In step 450, a vacuum is applied to the vacuum-based probe, thereby separating the target particles from the sample and holding them at the tip of the probe. As previously discussed, a vacuum can be applied to the probe by starting a vacuum pump and opening a solenoid valve, which allows the vacuum pump to draw air from outside the tip of the probe into the probe and back through the probe to the pump. The vacuum pump is in fluid communication with a hollow tube extending through the probe to allow airflow in this direction. The applied vacuum can be started and stopped by stopping the vacuum pump and / or closing and opening the solenoid valve. As previously discussed, a sufficient airflow is drawn into the probe to provide an attractive force at the tip of the probe, and the attractive force is sufficient to separate the target particles from the sample and hold the sample at the tip of the probe. In some embodiments, the attractive force used must be sufficient to overcome both gravity and any attractive forces between the target particles and the surface of the sample.

[0055] In some embodiments, step 450 further includes vertical downward movement of the probe toward the target particle (i.e., in the z-direction) as part of collecting the target particle. The vertical distance away from the target particle by the tip may be such that suction force alone is insufficient to pull the target particle away from the sample and up to the tip of the probe. Therefore, in order to provide sufficient suction force, the probe is moved vertically downward toward the target particle until the distance is reduced to a point where the suction force applied to the tip of the probe can pull the target particle away from the sample and up to the tip of the probe. While the probe is approaching the particle vertically, the airflow through the probe may be continuously monitored, for example, via a flowmeter as previously discussed and shown in Figure 2. Detection that the particle has been pulled up to the tip of the probe is determined when the flowmeter detects a sharp drop in flow rate, indicating that the particle is blocking the tip opening of the probe. The processor is configured to monitor and detect this drop in flow rate, and at this point the processor instructs the probe to stop its vertical movement toward the particle. This helps to ensure that the probe does not come into contact with (and therefore not damage) the particle.

[0056] In some embodiments, the vacuum suction provided by the probe may not be sufficient to lift the target particles away from the sample. In instances where competing forces (e.g., gravity, attractive forces between the particles and the substrate, etc.) are greater than the upward force supplied by the vacuum suction, the vacuum suction may not be sufficient. In some embodiments, steps may be taken to assist in lifting the target particles away from the sample. In one example, an inert liquid medium may be provided to the particles on the sample so that the particles are at least partially immersed in the inert liquid medium. The introduction of the inert liquid medium introduces an upward force due to buoyancy, which, combined with the suction force, may be able to overcome competing downward forces.

[0057] In another embodiment, the release of particles from the substrate may be facilitated by blowing air upward from beneath the particles. For example, the substrate on which the particles are deposited may include a series of punched holes from which air can be blown from an air supply source positioned beneath the substrate. In some embodiments, the position from which air is blown upward through the substrate may be selective. For example, the system (e.g., via a processor) may use pre-determined information about the position of the target particles (and used for probe positioning) to turn on upward blowing air only at the location of the target particles. Similarly, the system may be designed so that air is blown upward through the substrate only if it is determined that the suction force provided by the probe is not sufficient to lift the target particles away from the substrate. For example, as discussed previously, the airflow through the probe may be monitored while the probe is moving perpendicularly toward the target particles. If the probe tip moves within a predetermined distance of the target particle without recording a decrease in airflow through the probe, indicating that the target particle is being pulled upwards relative to the probe tip, the system (via the processor) instructs the air blowing system beneath the substrate to activate to provide an auxiliary upward force via air blowing up through the substrate at least in the vicinity of the target particle.

[0058] Once a particle is collected by the probe and held at the probe tip by a continuous vacuum force, the probe retracts (if it moved perpendicular to the particle) and moves laterally to a pre-specified retrieval position. Similar to determining the precise lateral position of the target particle, the pre-specified search position can also be assigned a specific height within the probe's range of movement. Once positioned appropriately, the vacuum is then stopped by sending an appropriate signal to a solenoid valve or by turning off the vacuum pump, resulting in the release of the particle from the probe to the pre-specified retrieval position.

[0059] The methods described above can be partially or fully automated so that the system performs the desired particle manipulation with minimal or no human intervention. Figures 5A and 5B provide two flowcharts illustrating semi-automatic and fully automated methods that can be performed by a processor communicatively coupled to other components of the system.

[0060] First, referring to Figure 5A, a semi-automatic method for particle manipulation is shown. The method in Figure 5A requires some human input, as will be explained in more detail below. This method is considered interactive due to the input provided by a human user as part of the process of performing the method. In short, the software executed by the processor follows these steps:

[0061] 1. The “Image Capture” button is pressed in the GUI associated with the system. As a result, a dark-field scattering image is acquired by the CCD camera, and the data is stored as a 16-bit array.

[0062] 2. The images obtained in step 1 are plotted on the GUI.

[0063] 3. Particles of interest within an image are identified by the user visually inspecting the image on a GUI. Input is provided to the system indicating the selected particle of interest (e.g., by a mouse click when the cursor is positioned over the particle of interest, or via the use of a touchscreen). This input records the particle's position.

[0064] 4. The “Particle Acquisition” button in the GUI is then pressed, initiating the particle handling procedure outlined in Figures 1 and 4, for example. As part of this procedure, the probe is moved to the correct lateral (x, y) position, vacuum is applied to the probe by sending an appropriate signal to the solenoid valve (opening the passage between the vacuum pump and the probe), and the probe begins to approach the substrate (movement in the z direction). During the probe's approach, the flow rate through the probe is continuously monitored, and if a significant change in flow rate is detected, the decrease in flow rate indicates the capture of a particle within the probe orifice, so the probe's movement in the z direction is stopped, the probe (with the particle held in it) is retracted (moved upward in the z direction away from the substrate), the probe is moved to a new pre-specified position, the vacuum to the probe is then released by sending an appropriate signal to the solenoid (closing the passage between the pump and the probe), and the probe returns to its initial position.

[0065] Referring here to Figure 5B, a fully automated method that requires no user input is outlined. The method in Figure 5B reflects in many ways the method shown in Figure 5A. The method in Figure 5B differs primarily in the initial step where particles of interest are automatically identified, rather than requiring user input to identify them. As shown in Figure 5B, the acquired image is analyzed to automatically generate a list of particles for rearrangement through the following process.

[0066] 1. The acquired images, stored as a 16-bit array, will be filtered using an appropriately sized Gaussian kernel to minimize features outside the size range of interest.

[0067] 2. A threshold will be provided to generate a binary image showing which pixels are associated with the particle of interest.

[0068] 3. For each adjacent active region in the binary image, the center of mass, which will function as the particle's position, will be calculated.

[0069] The method can be carried out in much the same way as described above in Figure 5A, where the user manually identifies the particles of interest.

[0070] The systems and methods described herein are highly customizable and directly applicable to many commercial, industrial, and advanced fields, including trace analysis fields such as nuclear forensics (certified by the U.S. Department of Energy), advanced technology manufacturers such as semiconductors, electronics, and smart materials, sensor technology, and academic laboratories. The trace analysis industry will benefit from the improved resolution and ability to manipulate specific particles in a non-destructive and non-contaminating manner with the systems and methods described herein. The disclosed systems and methods can also improve various micro and nanotechnologies by providing a platform that can non-destructively rearrange particulate materials into desired patterns without contamination. In one particular beneficial application, the systems and methods described herein can be used to precisely remove contaminating particles.

[0071] From the above explanation, while specific embodiments of the invention have been described for illustrative purposes, it should be understood that various modifications can be made without departing from the scope of the invention. Therefore, the invention is not limited except as provided for in the attached claims.

[0072] While the technology is described in language specific to particular structures and materials, it should be understood that the invention as defined in the attached claims is not necessarily limited to the specific structures and materials described. Rather, specific embodiments are described as forms that implement the claimed invention. Since many embodiments of the invention can be practiced without departing from the spirit and scope of the invention, the invention falls within the scope of the attached claims below.

[0073] Unless otherwise indicated, all numerical values ​​or expressions, such as dimensions and physical characteristics, used in the specification (excluding the claims) shall be understood in all instances to be modified by the term “approximately.” Not to the effect of attempting to limit the application of the doctrine of equivalents to the claims, each numerical parameter described in the specification or claims and modified by the term “approximately” should be interpreted at least by applying rounding techniques, taking into account the number of significant figures cited. Furthermore, all scopes disclosed herein should be understood to encompass and support any sub-scopes or claims enumerating any individual values ​​included herein. For example, the stated range of 1 to 10 should be considered to include and support claims that enumerate all subranges or individual values ​​between the minimum value of 1 and the maximum value of 10 and / or including these, i.e., all subranges that begin with a minimum value of 1 or more and end with a maximum value of 10 or less (e.g., 5.5 to 10, and 2.34 to 3.56, etc.), or any value between 1 and 10 (e.g., 3, 5.8, and 9.9994, etc.).

Claims

1. A particle manipulation system, An optical imaging system configured to acquire an image of a dry sample of particles, A processor configured to analyze the aforementioned image, wherein the image analysis includes at least identifying target particles or target clusters of particles within the image, and determining or recording the lateral position of the target particles or target clusters of particles within the dry sample of the particles, A sample transfer system, wherein a dry sample of particles can be placed in the sample transfer system, A vacuum-based probe system, A probe comprising a tapered hollow needle having an opening at its distal end, wherein the opening has a first diameter smaller than the target particle or target cluster of particles, A vacuum pump configured to apply vacuum up to the aforementioned probe, The vacuum-based probe system includes and Includes, The aforementioned processor, The probe, the sample transfer system, or both, are moved such that the probe is positioned laterally over the target particles or target clusters of particles within the dry sample of particles. Applying a vacuum to the probe so that the target particles or target clusters of particles are separated from the dry sample of particles and held at the tip of the probe. It is further configured to direct the vacuum-based probe system, the sample transfer system, or both, The vacuum-based probe system further includes a flow meter configured to monitor the airflow through the probe, The probe is configured to move vertically, The aforementioned processor, The probe is positioned laterally on the target particle or target cluster of particles within the dry sample of the particles, and after the vacuum is applied, the probe is moved vertically toward the target particle or target cluster of particles. While the probe is moving perpendicularly toward the target particle or target cluster of particles, the airflow passing through the probe is monitored via the flow meter. When a decrease in the airflow through the probe is measured by the flow meter, the vertical movement of the probe is stopped. Further configured to direct the vacuum-based probe system, Particle manipulation system.

2. The particle handling system according to claim 1, wherein the first diameter of the opening is in the range of 0.01 to 1,000 micrometers.

3. The aforementioned optical imaging system is An optical microscope configured to acquire an image of the dry sample of particles, A light source configured to illuminate the dry sample of particles, A camera configured to receive and record the aforementioned image and A particle manipulation system according to claim 1, comprising:

4. The particle manipulation system according to claim 3, wherein the optical imaging system is configured to perform dark-field optical microscopy.

5. The particle handling system according to claim 1, wherein the optical imaging system is configured to acquire a high-resolution image of a dry particle sample containing a plurality of particles having a size in the range of 0.01 to 1,000 micrometers.

6. The aforementioned processor, The particle manipulation system according to claim 1, wherein the sample moving system is configured to move the probe so that it is positioned laterally on the target particle or target cluster of particles within the dry sample of particles, while maintaining the probe in a stationary position.

7. A method for manipulating nanoscale and micrometer-scale particles, To obtain magnified images of a dry sample of particles containing multiple particles having a size in the range of 0.01 to 1,000 micrometers, Analyzing the magnified image to identify the target particle or target cluster of particles, Determining the lateral position of the target particle or target cluster of particles within the dry sample of the particles, Moving a vacuum-based probe, a sample transfer system in which the dry sample of particles is placed, or both, such that the vacuum-based probe is positioned laterally over the target particles or target clusters of particles within the dry sample of particles, Vacuum is applied to the vacuum-based probe, thereby separating the target particles or target clusters of particles from the dry sample of particles, and the target particles or target clusters of particles are held at the tip of the vacuum-based probe. The vacuum-based probe is positioned laterally on the target particle or target cluster of particles within the dry sample of particles, and after vacuum is applied to the vacuum-based probe, the vacuum-based probe is moved vertically toward the target particle or target cluster of particles. The airflow through the vacuum-based probe is monitored while the vacuum-based probe moves perpendicularly toward the target particle or target cluster of particles. If the aforementioned decrease in airflow is detected, the vertical movement of the vacuum-based probe is stopped, The vacuum-based probe includes a tapered hollow needle having an opening at its distal end, the opening having a first diameter smaller than the size of the target particle or target cluster of particles. method.

8. The method according to claim 7, wherein obtaining the magnified image of the dry sample of particles includes using dark-field imaging.

9. The method according to claim 8, wherein the plurality of particles are fire-resistant particles.

10. The method according to claim 9, wherein dark-field imaging includes directing a light source onto the dry sample of particles at a predetermined angle of incidence.

11. The method according to claim 7, wherein the first diameter of the opening is in the range of 0.01 to 1,000 micrometers.

12. The further includes displaying the magnified image of the dry sample of the particles on a display, Analyzing the magnified image to identify target particles or target clusters of particles includes receiving user input to select particles or clusters of particles displayed on the display, thereby identifying the particles as target particles, or identifying the clusters of particles as target clusters of particles. The method according to claim 7.

13. The method according to claim 7, wherein analyzing the magnified image to identify target particles or target clusters of particles comprises analyzing the magnified image and using a machine vision algorithm to identify the target particles or target clusters of particles.

14. The method according to claim 7, wherein moving the vacuum-based probe, the sample transfer system on which the dry sample of particles is placed, or both, such that the vacuum-based probe is positioned laterally over the target particles or target clusters of particles within the dry sample of particles, includes moving the sample transfer system while maintaining the vacuum-based probe in a stationary position.

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