Patent Application
20220357265
This application claims the benefit of priority of European Application Serial No. 21172793.8, filed 7 May 2021, which is hereby incorporated by reference in its entirety.
The invention relates to a device and a system for bunching of sample particles.
Serial femtosecond crystallography (SFX) known from the prior art uses intense and short pulses of X-rays from a free-electron laser to record many snapshot diffraction patterns of particles, in particular protein crystals, that flow across the X-ray beam generated by an X-ray source. Serial femtosecond crystallography was developed primarily to overcome the issue of radiation damage that may occur in conventional particle crystallography using X-ray tubes or synchrotron radiation, for example. The exposure to the X-ray beam modifies the structure under investigation, requiring a relatively large structure size of the particles, in particular large crystals, which are often difficult to grow, and cryogenic temperatures, which may also modify the structure from the physiologically relevant one. The short pulses of the X-ray free-electron laser (XFELs) are detected and the resulting structural information gained before destruction of the particle under X-ray exposure takes place, allowing much greater exposures, and hence much smaller particles which do not need to be cryogenically cooled. However, the particle is completely vaporized after the X-ray exposure, so measurements must be carried out repeatedly, each time with a fresh particle. One way to accomplish that is to flow a slurry comprising many distributed particles in a liquid jet across the X-ray beam. However, the duty cycle of the X-ray pulses is low when comparing the duration of pulses to the duration between pulses. Therefore, to increase the chance of the X-ray pulses intercept the randomly arriving particles at the interaction region, a high concentration of particles must be injected, resulting in a low sample delivery efficiency (the fraction of injected particle intercepted by the X-ray pulses). In the contrary, a high concentration of particles distributed in the fluid often leads to clogging of the capillary used to deliver the particles into the X-ray beam. In practice, a low concentration of samples must be injected, resulting a low hit fraction (the fraction of X-ray intercepting a particle). Therefore, measurements must be carried out over a longer period of time to collect enough diffraction patterns from particles.
The object of the present invention is to provide a device and a system, which allow an efficient examination of particles distributed in a fluid by radiation, in particular X-ray radiation.
According to a first aspect of the present invention, the object is solved by a device according to claim 1. The device comprises a body, a fluid channel extending through the body, an acoustic wave guide embedded in the body, and an acoustic wave condenser embedded in the body. The fluid channel forms a fluid path through the body, such that the fluid channel is configured to guide a flow of a sample fluid, in which sample particles are distributed, through the fluid channel along the fluid path. The wave guide is configured to guide an acoustic reference wave, when transmitted via the body to the wave guide, to an application region of the fluid channel. The wave condenser at least partly forms the application region of the fluid channel.
Further, the wave condenser is configured to generate a standing acoustic wave in the application region from the reference wave when the wave guide guides the reference wave into the application region resulting in an acoustic force field in the application region, which pushes sample particles when entering the application region into at least one bunch of sample particles in the application region.
The device offers the advantage that particles distributed in a fluid and carried by a fluid flow through the fluid channel of the device can be concentrated by means of the device into a bunch within the application area. A plurality of particles is arranged in the bunch, such that the concentration of particles within this bunch is significantly higher than the concentration of particles within the fluid upstream of the application area. After the bunch of particles is generated by means of the device, the bunch may be transported downstream with the flow of the fluid to be subsequently examined by means of X-rays. However, it is also possible that the bunch to of particles generated in the application area of the fluid channel of the device is examined by means of the X-rays. In this case, the X-rays also penetrate the device.
The particles are preferably formed by crystals, in particular protein crystals, or cells.
Due to the increased concentration of the particles in the bunch by means of the device, a particularly high efficiency in the examination of the particles by means of X-rays is possible. If the X-rays are directed at the application area itself or at an area downstream of the application area rather than at a section of the fluid channel upstream of the application area, and if it is also ensured that the X-rays are directed at the bunch of particles generated by means of the device, then there is a significantly higher probability that the X-rays will encounter at least one of the particles in the bunch. The interaction with the particles modifies the X-radiation so that the resulting modified X-radiation is detectable by means of a detector. Based on the measured, modified X-ray radiation, information about the structural configuration of the particles can be obtained.
To achieve the bunching of the particles in the application area, the device comprises a body, wherein the fluid channel of the device extends through the body. The fluid channel thus serves to carry a fluid, which is also referred to as a sample fluid. Within the fluid, the particles are distributed. The particles may also be referred to as sample particles. The fluid channel forms a fluid path through the body, such that the fluid channel guides the fluid in a transport direction along the fluid path. An initial concentration of sample particles distributed in the sample fluid may exist at an inlet end of the fluid channel, where the sample fluid is introduced into the fluid channel. Preferably, the fluid channel extends from the inlet end to an outlet end. The application region of the fluid channel may be provided between these two ends. Thus, the application region of the fluid channel may be defined by a portion of the fluid channel disposed between the inlet-side end of the fluid channel and the outlet-side end of the fluid channel.
The application region of the fluid channel is at least partially formed by the wave condenser of the device. For example, in the application region of the fluid channel, a channel wall of the fluid channel may be completely or partially formed by the wave condenser. The wave condenser is configured to generate a standing acoustic wave in the application region based on a reference wave when said reference wave enters the application region of the fluid channel. By the wave condenser, the application area of the fluid channel may be shaped, for example, such that a maximum diameter of the application region of the fluid channel corresponds to half the wavelength of the reference wave, so that when the reference wave enters the application region, it is reflected from opposite inner sides of the application region of the fluid channel, thereby creating the standing acoustic wave. Thus, the wave condenser may be configured and/or formed to localize the acoustic force field in the application region. The acoustic force field may be an acoustic pressure field or may be a result of the acoustic pressure field. The standing acoustic wave causes an acoustic force field within the application area, which acts on the particles transported by the fluid into the application area, causing the particles to be compressed and/or concentrated into a bunch within the application area.
The particles distributed in the sample fluid will move in the presence of an acoustic force field when the acoustic properties of particles and sample fluid are different, which is preferably assumed. Such a difference may relate to an acoustic contrast factor, density of the particles and the fluid, compressibility of the particles and fluid, as well as sound speed of the particles and the fluid. The magnitude of the acoustic force of the acoustic force field on particles depends on several factors such as particle size, acoustic energy density, acoustic wave frequency, and acoustic contrast factor. The direction of movement of the particles in an acoustic field may depend on the acoustic contrast factor so that particles may move from a region of high to low or low to high pressure, but in either case, a concentration of the particles will take place. The high- and low-pressure regions are effectively produced by the acoustic standing wave. Preferably, a primary axial (PA) acoustic radiation force of the standing acoustic wave moves particles in the application region to the nodal plane of the standing acoustic wave. It can be for example used for lining up the particles to the middle of the application region of the fluid channel. A gradient of the acoustic force field from high pressure antinodes to the low-pressure nodes may also generate a primary lateral (PL) acoustic radiation force for the bunching of the particles within the application region of the fluid channel. The primary lateral (PL) acoustic radiation force may also cause a tapping of the particles, such that the particles can be held against the flow of the fluid in the application area. The wave condenser may be configured to create localized acoustic pressure zone with a high-pressure gradient. In the high-pressure gradient, the PL acoustic radiation force may hold particles within the application region against drag force of the fluid flow in transport direction and/or the PA acoustic radiation force may push particles to the middle of the channel, which supports and/or causes the particle bunching.
The wave condenser may form a resonance cavity for the acoustic reference wave in the application of the fluid channel. This resonance cavity may localize the acoustic force field in the application region. The wave condenser may be coupled to wave guide in the boundary of the fluid channel.
It has been found to be challenging to direct the acoustic reference wave into the application region. Therefore, in addition to the wave condenser, the device includes a wave guide configured to guide the acoustic reference wave. The wave guide and the wave condenser are both embedded in the body of the device, respectively. Further, the wave guide is preferably embedded in the body of the device such that when the acoustic reference wave encounters the body of the device, it is at least partially captured by the wave guide and directed into the application region of the fluid channel. Therefore, in order to generate the standing acoustic wave in the application region of the fluid channel, the wave guide and the wave condenser cooperate. In particular, due to the energetic effect of this interaction, the desired acoustic wave can be generated by means of the device in the application region with an intensity that allows the particles to be concentrated by means of the resulting acoustic force field.
In principle, the wave guide can be designed in very different ways. For example, the wave guide may be single-piece or multi-piece. The wave guide may also be formed as an integral part of the body of the device. In this case, the wave guide may be formed by one or more portions of the body of the device. It had been found to be advantageous if the wave guide forms at least two mutually spaced edges at which the acoustic reference wave is at least partially reflected. The edges are not necessarily formed by physical structural edges. The at least two mutually spaced edges may be disposed within the body of the device such that they guide the acoustic reference wave to the fluid channel application region. Each of the edges may be formed by a transition from one material to another material. Additionally or alternatively, each of the edges may be formed by a junction of an acoustic impedance within the body of the device. Each edge may therefore be created by a cavity within the body of the device.
The wave guide may be configured to cause a higher acoustic intensity to the application region. As a result, the acoustic reference wave can be generated by normal size transducers instead of small ones to transfer the acoustic power of a large area to small area in microfluidic chip. The small (micron) size transducers have challenges in fabrication, soldering, and implementation in microfluidic device for such application The power of the small size acoustic transducer may be deliberately concentrated by the wave guide to the application region of the fluid channel instead of attenuating it because of actuating the entire body or device.
The body of the device may be formed as a chip. The body material of the body may be chip material. The chip may be a glass chip. However, the chip may also be formed at least partly by different material.
According to a preferred embodiment of the device, the fluid channel is formed by the body. The fluid channel may be formed as an integral part of the body. This integration may prevent further acoustic impedance step or acoustic impedance mismatch in the transition from the body to the fluid channel. The wave condenser forms at least part of the application region of the fluid channel. It is therefore preferred that the wave condenser is also formed as an integral part of the body of the device. In other words, the wave condenser may be formed by the body of the device. In principle, however, it is also possible that the fluid channel is formed by at least one separate part embedded in the body of the device. The multi-part design of the body can simplify manufacturing. The wave condenser may be one of said parts for forming the fluid channel. Thus, in this case, it is possible that the wave condenser is formed as a separate part and is embedded in the body of the device. In particular, when the fluid channel and/or the wave condenser are each formed as a separate part, it may be provided that the body of the device is formed of a plurality of parts. In other words, the body of the device may be formed in multiple parts. However, it is also possible that the body of the device is formed in one piece. In this case, it is preferred that both the fluid channel and the condenser are integrally formed by the body of the device.
According to a further preferred embodiment of the device, the wave guide is formed by the body. Preferably, the wave guide is an integral part of the body of the device. The integral design of the wave guide allows particularly precise guiding of the acoustic reference wave into the application region of the fluid channel.
According to a further preferred embodiment of the device, the wave guide is formed by at least one cavity in the body. Preferably, the wave guide is formed by at least two cavities in the body of the device. Preferably, the wave guide is formed by exactly two separated cavities in the body. With at least two cavities, the cavities may be spaced apart such that the wave guide is formed to direct the acoustic reference wave in the region of the body between the cavities to the application region of the fluid channel. Each cavity may be formed as a closed cavity. Each cavity may create a reflective boundary for the acoustic reference wave. Preferably, each cavity has an acoustic impedance different to the acoustic impedance of the body material of the body. Due to the different acoustic impedance, the acoustic reference wave can be reflected at each of the cavities, and thus be guided into the application area of the fluid channel.
According to a further preferred embodiment of the device, each cavity is a gas filled cavity or a vacuum cavity. Preferably, each cavity of the wave guide is filled with air. Air is considered an embodiment of the broad term gas. The body material of the body of the device is preferably not gaseous, but preferably of a solid material. Therefore, the body of solid material may have the at least one resting cavity placed in it. The wave guide formed by the at least one cavity can be arranged in a particularly compact manner in the body of the device. Thus, a particularly compact device can be achieved.
According to a further preferred embodiment of the device, the wave guide is formed by at least two cavities and a guiding section, which is formed by body material of the body, wherein the guiding section is arranged in between the cavities and configured to transmit the acoustic reference wave into the application region. As an effect, the acoustic wave will be reflected on each transition from body material to air, so that the acoustic wave remains in the guiding section formed by body material until it reaches the application region of the fluid channel. An acoustic reference wave entering the body material of the body of the device may thus be guided to the fluid channel application area with little attenuation loss. Preferably, a width of the guiding section is larger than the wavelength of the acoustic reference wave, such that the acoustic reference wave can be transmitted by the guiding section.
The wave guide may be configured, in particular by means of the at least two cavities and body material in between, to operate according to the principle of reflection and transmission of the acoustic wave. The cavities may each create a reflective boundary due to the difference between the acoustic impedance of the body material and the cavity. Such boundaries may reflect the acoustic reference wave and guide it to the application region of the fluid channel. The thickness of the guiding section between the cavities may be adjusted so that the acoustic reference wave can be transmitted.
According to a further preferred embodiment of the device, the guiding section comprises a conical shape tapering in direction of the application region of the fluid channel. This allows the intensity of the acoustic reference wave in the application area to be particularly high. Preferably, a diameter of the guiding section or a distance between the cavities is tapering in direction of the application region. The conical or tapered shape allows the acoustic reference wave to be collected from a wide area and directed into the application area in a concentrated manner. Thus, the conical shape of the guiding section may be formed to direct the acoustic wave into the application region. Preferably, the guiding section is formed as a guiding horn, in particular a micro-horn. Preferably, the guiding section is configured to collect the acoustic reference wave when entering the body or the body material of the body.
The wave guide and/or the wave condenser may be integrally formed in the body by femtosecond laser induced chemical etching (FLICE) or two-photon polymerization (2PP).
The ability of the FLICE techniques in creating complicated 3D structures in glass allows fabrication of the wave guide as 3D wave guide or the wave condenser as 3D wave condenser. Such an acoustic wave guide may be configured to guide the acoustic reference wave in any 3D directions towards the application region of the fluid channel.
Furthermore, the wave guide may be configured to guide the acoustic reference wave along a predefined path in the body of the device. The predefined path may be linear, curved or along a predefined arbitrary shaped trajectory. Thus, the acoustic reference wave entering the body material of the body may be guided in curved path by the wave guide to the application region of the fluid channel.
According to a preferred embodiment of the device, the wave guide may be formed as mufti-functional microstructures. This may be achieved by structural modifications inside the wave guide, preferably without deteriorating the traveling guiding ability of the acoustic reference wave. This may introduce different energy domains. In an example, the wave guide may comprise narrow fluid channels inside (preferably formed via FLICE or 2PP techniques), wherein the inside channels allow introduction of further fluid to the application region. This further fluid could be of interest for applications such as drug delivery or cancer therapy investigations. It is also possible to integrate optical sub-wave guides inside the wave guide of the device. The sub-wave guides may be created by FLICE technique.
According to a further preferred embodiment of the device, the wave condenser is formed by at least one concave-shaped wall section of a channel wall for the fluid channel, wherein the at least one wall section at least partly forms the application region of the fluid channel. Each concave-shaped wall section increases the width of the fluid channel. The concave-shape of the wave condenser may support the technical effect of localizing the standing acoustic wave in the application region of the fluid channel. Each concave-shaped wall section is preferably configured to reflect at least a part of the acoustic reference wave entering the application region. Each concave-shaped wall section has an acoustical impedance to reflect the acoustic reference wave. Thus, the acoustic reference wave guided to the wave condenser via the wave guide may be at least partly transmitted through the channel wall into the application region of the fluid channel, where the transmitted acoustic reference wave is at least partly reflected on the inside surface of the concave-shaped wall section resulting in the standing acoustic wave. As a result, the wave condenser is preferably configured to localize the acoustic force field in the application region of the fluid channel. In an example, each concave-shaped wall section may be formed as a bowl. Each concave-shaped wall section may be of micro-size. At least two concave-shaped wall sections may be arranged opposite each other in the radial direction of the fluid channel, in particular in the application region of the fluid channel. The body material of the body of the device surrounding the wave condenser may be configured not to resonate with the acoustic reference wave.
According to a further preferred embodiment of the device, at least one edge is formed in a transition area from a linear wall section of the channel wall to the at least one concave-shaped wall section of the channel wall. Preferably, an edge is formed at each transition from a linear section of the channel wall to a concave shaped wall section of the channel wall. Each, concave shaped wall section projects outwardly rather than inwardly into the fluid channel such that the application region of the fluid channel is enlarged by each concave shaped wall section of the channel wall. Preferably, the fluid channel is formed upstream from the application region by a linear wall section of the channel wall. This linear wall section may be circular-cylindrical. Furthermore, it is preferably provided that the fluid channel downstream from the application region is formed by a further linear wall section of the channel wall. This linear wall section may also be circularly cylindrical. Each edge may cause a streaming in the application region of the fluid channel. The streaming may also refer to as circular streaming or spiral streaming. The streaming may be formed by fluid in the application region set into circulatory motion by the edge. As a result, the fluid may circulate in within the application region right next to the edge. The streams and/or the circulating fluid may cause (further) force pushing particles entering the application region towards the center of the application region. This further supports the bunching of the particles. As a result, both, the streaming and the standing acoustic wave support and/or cause the bunching of particles in the application region.
According to a further preferred embodiment of the device, the wave condenser is formed by two opposite arranged wall sections of the channel wall or a single ring-shaped wall section of the channel wall. For example, the wave condenser may be formed by two opposite arranged concave-shaped wall sections. Each concave-shaped wall section may have the form of a bowl. For example, the ring-shaped wall section can be formed by the radially outer half of a torus.
According to a further preferred embodiment of the device, the application region of the fluid channel is at least partly formed by the wave condenser such that a reference width of the application region perpendicular to a transport direction of the fluid channel matches a half wavelength of the reference wave with a tolerance of less than 10% of the half wavelength of the reference wave. The width of the application region is preferably the maximum width of the channel in the application region. Preferably, the reference width is measured in a direction perpendicular to the transport direction in the application region. When an acoustic reference wave enters the application region of the fluid channel, it is reflected from the opposite inner sides of the wave condenser. To generate the standing acoustic wave, it is advantageous if the reference width between the opposite inner sides of the wave condenser corresponds to half the wavelength of the acoustic reference wave. Often, the acoustic reference wave does not have exactly a single wavelength, but the acoustic reference wave has a predetermined wavelength spectrum. When the wavelength of the acoustic reference wave is referred to, this preferably means an average wavelength of the predetermined wavelength spectrum. Against this background, a standing acoustic wave can be achieved within the application region even if the reference width of the application region or the wave condenser does not exactly correspond to half the wavelength of the acoustic reference wave, but has a certain deviation. This deviation is preferably called tolerance and is preferably smaller than 10% or 5% of the half wavelength of the acoustic reference wave.
According to a further preferred embodiment of the device, the body is a monolithic body. Preferably, the body is made as a single piece. This allows a particularly compact design of the device.
According to a further preferred embodiment of the device, the body material of the body is based on glass, silicon, metal, diamond, sapphire or plastic. Preferably, the body material is glass, silicon, metal, diamond, sapphire, ceramic or plastic.
According to a second aspect of the invention, the problem mentioned at the introduction is solved by a system comprising the features of claim 14. The system comprises a first wave generator, which is configured to generate a first acoustic reference wave, a fluid pump for generating a flow of sample fluid, and a first device. The first device is formed by a device according to the first aspect of the invention and/or one of the related preferred embodiments. The advantageous explanations, preferred features, technical effects and/or advantages as explained in connection with the first aspect of the device and/or the related preferred embodiments are referred to in an analogous manner for the first device of the system. Furthermore, the fluid pump of the system is directly or indirectly coupled to the fluid channel of the first device for pumping the sample fluid through the fluid channel of the first device. The first wave generator is directly or indirectly coupled to the first device such that the first acoustic reference wave, generated by the first wave generator, is transmitted to the wave guide of the first device.
Preferably, the wave generator is connected to the body of the first device such that the first acoustic reference wave generated by the first wave generator is transmitted to the body material of the body of the first device. For transmitting the first acoustic reference wave from the first wave generator to the body material of the body, alternatively, another transmission element may be used that is arranged between the first wave generator and the body of the first device. In this case, the first wave generator is indirectly coupled to the first device. Nevertheless, a transmission of the first acoustic reference wave from the first wave generator to the body of the first device takes place.
According to a preferred example, the first wave generator is configured to generate an acoustic reference wave with a reference frequency of more than 7.5 MHz. Thus, the equivalent half wavelength of the acoustic reference wave is preferably less than 100 micrometers. However, the acoustic reference wave is not limited to the aforementioned frequency. In practice, the frequency of the acoustic reference wave may depend on the particular design of the device for the application. In particular, a higher frequency for the acoustic reference wave can be advantageous if particularly small particles, for example sub-micron particles, are to be examined.
Particles may be distributed in an initial concentration in the fluid that is pumped in by the fluid pump at an inlet end of the fluid channel. The pump causes a fluid flow of the fluid through the fluid channel, which transports the particles carried by the fluid into the application region. Particles entering the application region are exposed to the standing acoustic wave and the resulting force field, creating the bunch of particles within the application region. The standing wave is caused by the acoustic reference wave. Initially, the reference acoustic wave is generated by the first wave generator, then transmitted to the body of the first device and guided within the body by the wave guide to the application region. Within the application region, the acoustic reference wave is converted into the acoustic standing wave by the wave condenser.
By regularly switching on and off the first wave generator, a sequence of bunches of particles can be generated, which leave the application region one after the other and are further transported by the fluid flow in the transport direction downstream along the fluid channel.
The bunches of particles generated in the application region can subsequently be exposed to radiation to examine the structural composition of the particles. Due to the high concentration of particles within the bunch, these examinations can be carried out particularly efficiently.
According to a preferred embodiment of the system, the system comprises a second device. The second device is formed by another device according to the first aspect of the invention and/or one of the related preferred embodiments. The advantageous explanations, preferred features, technical effects and/or advantages as explained in connection with the first aspect of the device and/or the related preferred embodiments are referred to in an analogous manner for the second device of the system. Alternatively or additionally, the second device may be configured analogously to the first device. The fluid channel of the first device and the fluid channel of the second device are connected in series, such that the fluid channel of the second device is downstream to the fluid channel of the first device.
The first device and the second device may be formed in an integral manner, so that the two devices are formed as a single device. This single-piece device may thus be formed in a first section by the first device and in a further, second section by the second device.
However, it is also possible, that the first device and the second device are each formed as separate devices. Preferably, the two devices are connected in series such that the fluid channel of the first device and the fluid channel of the second device each form part of an uninterrupted fluid channel. In particular, it is possible for the second device to be coupled directly downstream of the first device such that the uninterrupted fluid channel is formed exclusively by the fluid channel of the first device and the fluid channel of the second device. However, it is also possible that another device is arranged between the two devices with an associated fluid channel connecting the two fluid channels of the first and second devices.
As a result of the direct or indirect series connection of the fluid channels of the first and second devices, the system comprises at least two application regions located along the common channel (that is, in series) so as to successively improve the bunching. This might be of advantage at high flow rates and high bunching rates when there might not be enough time during one cycle to create a narrow bunch. The application regions could be located in a single integrated body forming both devices, or each in its own device (first and second device, respectively) with the fluid channels connected by capillaries, for example. The spacing of the application regions may be determined by the flow speed and the bunching period. Given that the period may be determined by the application, one would need to set the flow speed to ensure synchronization (that the bunching action in the application region of the fluid channel of the second device occurs when the bunch released form the application region of the fluid channel of the first device arrives).
According to a further preferred embodiment of the system, the system comprises a control unit. The control unit is configured to control the first wave generator such that the first wave generator generates the first reference wave in a first pattern with alternating on-periods and off-periods resulting in a new first bunch of sample particles in the application region of the fluid channel of the first device during each on-period of the first pattern. As a result, a new bunch of particles is created in the application region of the fluid channel of the first device.
As will become apparent from the explanation of one of the following preferred embodiments of the system, a newly created bunch of particles may be exposed to radiation while still within the application region to examine the structural constitution of the particles of the bunch. Alternatively, however, it is also possible for a newly created bunch of particles to be released at the end of the corresponding on-period from the application region resulting in a sequence of bunches carried by the flow of fluid downstream of the application region of the first device. The bunches of particles carried downstream by the fluid may be exposed to radiation downstream to perform the appropriate examination of the particles.
Before the bunches created by the first device are exposed to radiation, it is possible that the particles are further concentrated within the respective bunch. For this purpose, the second device already explained may be used, which can be coupled in series with the first device.
According to a further preferred embodiment of the system, the system comprises a second wave generator, which is configured to generate a second acoustic reference wave. The second wave generator is directly or indirectly coupled to the second device such that the second acoustic reference wave, generated by the second wave generator, is transmitted to the wave guide of the second device. The advantageous explanations, preferred features, technical effects and/or advantages as explained in connection with the first wave generator and the first device and/or the related preferred embodiments are referred to in an analogous manner for the second wave generator and the second device, respectively.
According to a further preferred embodiment of the system, the control unit is configured to control the second wave generator such that the second wave generator generates the second reference wave in a second pattern with alternating on-periods and off-periods. Preferably, the control unit is configured to control the first and second wave generators, such that the second pattern is synchronized with the first pattern and/or such that the particles are further concentrated in the bunches that sequentially enter the application region of the fluid channel of the second device.
According to a further preferred embodiment of the system, the system comprises a radiation generator and a radiation detector. The radiation generator is arranged such that the application region of the fluid channel of the first or second device is exposed to radiation generated by the radiation generator resulting in modified radiation, and wherein the radiation detector is arranged to detect the modified radiation. The radiation preferably refers to X-ray radiation or IR radiation. The radiation may also refer to visible light or to UV light. Similar configurations apply for the generator and the detector. For instance, the radiation generator is preferably configured as an X-ray generator and the radiation detector is preferably configured as an X-ray detector.
As explained in connection with the device, the wave guide of the first and/or second device may be configured to guide the acoustic reference wave along a predefined path in the body of the respective device. The predefined path may be linear, curved or along a predefined arbitrary shaped trajectory. Thus, the acoustic reference wave entering the body material of the body of the respective device may be guided in curved path by the wave guide to the application region of the fluid channel of the respective device. As an effect, the first and/or second wave generator may be arranged at a side region of the body of the respective device, wherein the radiation generator is arranged below the application region of the fluid channel of the respective device and the detector may be arranged above this application region, such that the application region is exposed to the radiation generated by the radiation generator. The preferred arrangement of the radiation generator below the application region and of the radiation detector above the application region offers the advantage that the radiation generated by the radiation generator is directed to the bunch within the application region where the particles within the bunch have the highest concentration. This is especially valid if the radiation generator is located below the application region of the fluid channel of the second device and the radiation detector is located above said application region.
Further features, advantages and application possibilities of the present invention may be derived from the following description of exemplary embodiments and/or the figures. Thereby, all described and/or visually depicted features for themselves and/or in any combination may form an advantageous subject matter and/or features of the present invention independent of the combination in the individual claims or the dependencies. Furthermore, in the figures, same reference signs may indicate same or similar objects.
The device 10 is used to bunch particles 12 within an application region 26, such that the bunched particles 12 form a bunch 28 of particles 12. The bunch 28 may also be referred to as the first bunch 28. Bunching the particles 12 in a bunch 28 provides the advantage that this bunch 28 can be exposed to radiation, in particular X-rays, to examine the structural constitution of the particles 12 of the bunch 28. Due to the increased concentration of particles 12 within the bunch 28, there is a high probability that a large portion of the radiation will be modified upon impingement on the particles 12 of the bunch 28, such that the resulting modified radiation represents the information regarding the structural composition of the particles 12 of the bunch 28.
To achieve the bunching of particles 12, the device 10 includes a body 14, a fluid channel 16, an acoustic wave guide 18, and an acoustic wave condenser 20.
The body 14 of the device 10 may also be referred to as the base body 14. The body 14 may be formed in one part or in multiple parts. Preferably, the body 14 is made of glass, silicon, metal, diamond, sapphire, ceramic or plastic. Accordingly, the same applies to the body material 34 of the body 14. Where the body 14 is formed of multiple parts, the parts may be formed of different materials, preferably each based on a material from the aforementioned selection of materials.
The fluid channel 16 of the device 10 extends through the body 14, and it can therefore also be referred to that the fluid channel 16 is embedded in the body 14 of the device 10. It has been found to be particularly advantageous if the fluid channel 16 is integrally formed by the body 14. As schematically shown in
The fluid channel 16 defines a fluid path 22 along which a fluid 24 is routed through the fluid channel 16 in the transport direction 44. The system 46 shown in
Therefore, the device 10 is based on the idea of significantly increasing the concentration of particles 12 in the fluid 24 in an application region 26 within the device 10 to create bunches 28 of particles 12 in the fluid 24, such that more efficient investigation of the structural composition of the particles 12 is enabled. To achieve the increased concentration of particles 12 in a bunch 28, the device 10 includes the acoustic wave guide 18 and the acoustic wave condenser 20.
The acoustic wave guide 18 may also be referred to as the wave guide 18. The acoustic wave guide 18 is configured to direct an acoustic reference wave within the body 14, which acoustic reference wave is preferably generated by the first wave generator 48 of the system 46. For this purpose, the wave generator 48 may be directly or indirectly connected to the body 14 such that the reference acoustic wave generated by the wave generator 48 is transported by the body material 34 of the body 14. The wave guide 18 directs the reference acoustic wave within the body 14 to the application region 26 of the fluid channel 16, such that the reference acoustic wave enters the application region 26 of the fluid channel 16.
It had been found to be particularly advantageous if the wave guide 18 is integrated into the body 14 and/or formed by the body 14. As can be seen schematically from
Preferably, the wave condenser 20 of the device 10 is formed by the body 14 and/or is formed as an integral part of the body 14. As can be seen schematically from
The shape of the acoustic wave condenser 20 is preferably configured such that the standing acoustic wave generated in the application region 26 remains localized and/or retained in the application region 26. This ensures a particularly effective bunching of the particles 12 in the application region 26.
The bunching of the particles 12 in the application region 26 can be intensified and/or improved by an additional effect. To achieve this effect, an edge 38 is preferably formed in at least one transition region from a linear wall section 40 of the channel wall to the at least one concave shaped wall section 36 of the channel wall. As can be seen schematically from
A further preferred embodiment of the device 10 is schematically shown in
In the preferred embodiment of the device 10, as exemplified schematically in
As can be seen schematically from
In
The device 10 of
As has been previously explained in connection with
It was found to be particularly advantageous if the system 46 further comprises a control unit 60 configured to control the first wave generator 48. For example, the control unit 60 may be configured to control the first wave generator 48 such that the first wave generator 48 generates the acoustic reference wave in a first pattern of alternating on-periods and off-periods. During each new on-period, a new bunch of particles 12 is generated in the application region 26 of the fluid channel 16 of the device 10. During each subsequent off-period, the generated bunch 28 of particles 12 is released, captured by the flow of fluid 24, and transported in the transport direction 44.
In addition, it has been found to be particularly advantageous if the system 46 further comprises a radiation generator 62 and a radiation detector 64. The radiation generator 62 is configured to generate radiation. The radiation may be, for example, X-rays or infrared radiation. The radiation may also be visible light or UV light. Accordingly, it is preferred if the radiation generator 62 is configured as an X-ray radiation generator 62 or an infrared radiation generator 62. In the foregoing embodiment of the system 46 as schematically shown in
As can be seen schematically from
Another preliminary embodiment of the system 46 is shown schematically in
Preferably, the first device 50 and the second device 54 are connected in series such that the fluid channel 16 of the first device 50 is coupled downstream to the fluid channel 16 of the second device 54. In principle, however, it is also possible that the fluid channel 16 of the first device 50 is connected to the fluid channel 16 of the second device 54 by a (further) connector. This is shown purely by way of example in
However, if the first device 50 is directly coupled to the second device 54, a particularly compact design of the system 46 can be achieved. A further advantageous embodiment (not shown) is characterized in that the first device 50 and the second device 54 are at least partially integrally formed with each other or are formed by two portions of a common device.
By arranging the second device 54 downstream of the first device 50, the flow of the fluid 24 is directed through two application regions 26 arranged one behind the other, namely first through the application region 26 of the first device 50 and then through the application region 26 of the second device 54. Therefore, it can also be referred to that the fluid channel 16 of the first device 50 and the fluid channel 16 of the second device 54 form a common fluid channel of the system 46. In the application region 26 of the first device 50, the particles 12 are concentrated into a bunch 28. When this bunch 28 of particles 12 is released in the out-period and caught by the flow of fluid 24, the fluid 24 carries the bunch 28 of particles 12 into the application region 26 of the second device 54. A standing wave is also created in this application region 26 of the second device 54 during the associated on-period, such that the resulting force field further concentrates the particles 12 of the bunch 28 when this bunch 28 has previously entered the application region 26 of the second device 54.
The body 14 of the second device 54 may include a neck section 74, wherein a second wave generator 76 is disposed at the end of the neck section 74. The second wave generator 76 may form part of the system 46. The neck section 74 may direct the reference acoustic wave generated by the second wave generator 76 to the wave guide 18 of the second device 54, such that the wave guide 18 of the second device 54 directs the reference acoustic wave into the application region 26 of the fluid channel 16 of the second device 54. The wave condenser 20 of the second device 54 then generates a standing acoustic wave in the application region 26 of the second device 54 based on the reference acoustic wave. The neck section 74 further provides the advantage that the radiation generator 62 and the radiation detector 64 may be disposed on opposite sides of the application region 26 of the second device 54, without the radiation generated by the radiation generator 62 being disturbed by the second wave generator 76.
By further concentrating the particles 12 of the bunch 28 in the application region 26 of the second device 54, an even more efficient examination of the structural composition of the particles 12 can be performed using the modified radiation detected by the radiation detector 64.
It is additionally pointed out that “comprising” does not rule out other elements, and “a” or “an” does not rule out a multiplicity. It is also pointed out that features that have been described with reference to one of the above exemplary embodiments may also be disclosed as in combination with other features of other exemplary embodiments described above. Reference signs in the claims are not to be regarded as restrictive.
10 Device
12 sample particle
14 body
16 fluid channel
18 wave guide
20 wave condenser
22 fluid path
24 fluid
26 application region
28 first bunch
30 cavity
32 guiding section
34 body material
36 concave-shaped wail section
38 edge
40 linear wail section
42 reference width
44 transport direction
46 system
48 first wave generator
50 first device
52 fluid pump
54 second device
60 control unit
62 radiation generator
64 radiation detector
66 bottom part
68 top part
70 connector
72 application area
74 neck section
76 second wave generator
| Number | Date | Country | Kind |
|---|---|---|---|
| 21172793.8 | May 2021 | EP | regional |
