Bioparticle Concentration Apparatus, Bioparticle Concentration Device, and Pico-Droplet Generator

Abstract

To provide a bio-particle concentration apparatus for quickly and accurately performing a concentration process.SOLUTION: There are provided a bio-particle concentration apparatus, a bio-particle concentration device, and a pico droplet generator 100. The pico droplet generator includes an optical sensing structure 1, a fitting structure 2 arranged at an interval from the optical sensing structure, a bonding layer 3 for connecting the optical sensing structure and the fitting structure, and a piezoelectric member 4 arranged on the bonding layer. The pico droplet generator defines a selection channel 5 in a flow direction. The bonding layer has a selection hole 33 spatially communicating with the selection channel in a liquid discharge direction perpendicular to the flow direction. The piezoelectric member and the selection hole are arranged on the two sides of the bonding layer, respectively. The pico droplet generator has a pico droplet discharge region defined in a direction of the piezoelectric member from the selection hole.SELECTED DRAWING: Figure 2

Description

[Technical field]

[0001] The present invention relates to droplet generators, and more particularly to bioparticle concentration apparatus, bioparticle concentration devices, and pico-droplet generators. [Background technology]

[0002] The enrichment process is the first step in the traditional research of bioparticles, but the traditional enrichment process still requires a large amount of manpower. Therefore, how to use an apparatus or device to quickly and accurately carry out the enrichment process is one of the important areas of research and development in related fields. Therefore, the inventor thought that the above-mentioned shortcomings could be improved, and studied and applied scientific principles, and finally arrived at the present invention, which is rationally designed and effective in improving the above-mentioned shortcomings. Summary of the Invention [Problem to be solved by the invention]

[0003] In response to the above technical deficiencies, the present invention provides a bioparticle concentrating apparatus, a bioparticle concentrating device, and a pico-droplet generating apparatus to effectively improve the problems associated with the conventional concentration process. [Means for solving the problem]

[0004] In order to solve the above problems, one of the technical aspects adopted by the present invention is to provide a bioparticle concentration device for sorting at least one bioparticle from bioparticles in a liquid sample. The bioparticle concentration device includes a pico-droplet generating device, a power supply device, a pressure balance device, a camera device, and a control device. The pico-droplet generating device includes an optical sensing structure, Opposing structure The optical sensing structure includes a first substrate, a first electrode layer and a photoelectric layer respectively formed on both sides of the first substrate, and an insulating layer covering the photoelectric layer. Opposing structure is disposed at a distance from the light sensing structure. Opposing structure and at least one of the optical sensing structures is transparent; Opposing structureThe bonding layer includes a second substrate and a second electrode layer formed on the second substrate and facing the light sensing structure. The bonding layer is bonded to the light sensing structure along a thickness direction. Opposing structure , which together define a sorting channel along the flow direction perpendicular to the thickness direction. Opposing structure and at least one of the bonding layers has an inlet located upstream of the sorting channel and an outlet located downstream of the sorting channel. The bonding layer has a sorting hole spatially communicating with the sorting channel along an outflow direction perpendicular to the thickness direction and the flow direction. The piezoelectric member is disposed on the bonding layer. The piezoelectric member and the sorting hole are disposed on two opposing sides of the bonding layer, respectively, along the outflow direction. The pico droplet generator has a pico droplet emission region defined by extending from the sorting hole toward the piezoelectric member. The power supply is electrically coupled to the first electrode layer and the second electrode layer. The pressure balance device includes a first valve assembled to the inlet and a second valve assembled to the outflow port. The pressure balance device is configured to control a velocity and a pressure of the liquid sample in the sorting channel via the first valve and the second valve. The camera device is positioned corresponding to a viewable segment of the sorting channel. The pico droplet emission region is disposed within the viewable segment, and the camera device is configured to acquire a real-time image of the liquid sample in the viewable segment. A controller is electrically coupled to the piezoelectric member, and when a real-time image captured by the camera device indicates at least one of the bioparticles located within the picodroplet emission region, the controller drives the piezoelectric member to output the picodroplet by driving the liquid sample within the picodroplet emission region through the sorting hole to form the bioparticle-covered picodroplet.

[0005] In order to solve the above problems, another technical aspect adopted by the embodiment of the present invention is to provide a bioparticle concentration device for selecting target bioparticles from a liquid sample containing bioparticles. The bioparticle concentration device includes a pico-droplet generation device and a light source mechanism. The pico-droplet generation device includes an optical sensing structure, Opposing structureThe optical sensing structure includes a first substrate, a first electrode layer and a photoelectric layer formed on two opposing sides of the first substrate, respectively, and an insulating layer covering the photoelectric layer. Opposing structure is disposed at a distance from the light sensing structure. Opposing structure and at least one of the optical sensing structures is transparent; Opposing structure The bonding layer includes a second substrate and a second electrode layer formed on the second substrate and facing the light sensing structure. The bonding layer is bonded to the light sensing structure along a thickness direction. Opposing structure , which together define a sorting channel along the flow direction perpendicular to the thickness direction. Opposing structure and at least one of the bonding layers has an inlet located upstream of the sorting channel and an outlet located downstream of the sorting channel. The bonding layer has a sorting hole spatially communicating with the sorting channel along an outflow direction perpendicular to the thickness direction and the flow direction. The piezoelectric member is disposed on the bonding layer. The piezoelectric member and the sorting hole are disposed on two opposite sides of the bonding layer along the outflow direction, respectively. The pico-droplet generator has a pico-droplet emission region defined by extending from the sorting hole toward the piezoelectric member. The light source mechanism is configured to radiate light to the bio-particles to apply a dielectrophoretic (DEP) force to the target bio-particles through the light sensing structure, thereby moving the target bio-particles to the pico-droplet emission region. The piezoelectric member is configured to output the pico-droplet by driving the liquid sample in the pico-droplet emission region through the sorting hole, forming the pico-droplet covered with the bio-particles.

[0006] In order to solve the above problems, another technical aspect adopted by the present invention is to provide a pico-droplet generating device. The pico-droplet generating device includes an optical sensing structure, Opposing structure The optical sensing structure includes a first substrate, a first electrode layer and a photoelectric layer formed on two opposing sides of the first substrate, respectively, and an insulating layer covering the photoelectric layer. Opposing structure is disposed at a distance from the light sensing structure. Opposing structure and at least one of the optical sensing structures is transparent; Opposing structure The bonding layer includes a second substrate and a second electrode layer formed on the second substrate and facing the light sensing structure. The bonding layer is bonded to the light sensing structure along a thickness direction. Opposing structure and jointly define a sorting channel along the flow direction perpendicular to the thickness direction. Opposing structure and at least one of the bonding layers has an inlet located upstream of the sorting channel and an outlet located downstream of the sorting channel. The bonding layer has a sorting hole in spatial communication with the sorting channel along an exit direction perpendicular to the thickness direction and the flow direction. The piezoelectric member is disposed on the bonding layer. The piezoelectric member and the sorting hole are disposed on two opposite sides of the bonding layer, respectively, along the exit direction. The picodroplet generator has a picodroplet emission area defined by extending from the sorting hole toward the piezoelectric member. Effect of the Invention

[0007] As shown above, the pico-droplet generator configuration of the bioparticle concentrator provided by the present invention can be used to rapidly and accurately perform the sorting and concentration process of bioparticles (or at least one target bioparticle) through a piezoelectric member. The pico-droplet generator of the present invention has a configuration that allows for mass production, thereby facilitating a reduction in the overall cost of the bioparticle concentrator.

[0008] In addition, the pico-droplet generating device and the light source mechanism of the bio-particle concentrating device provided by the present invention can be used in cooperation with each other to quickly and accurately ensure that the pico-droplet emitting area has at least one target bio-particle, so that the pico-droplet can be formed to collect at least one target bio-particle.

[0009] In order to better understand the characteristics and technical contents of the present invention, please refer to the following detailed description of the present invention and the accompanying drawings, which do not limit the protection scope of the present invention in any way. [Brief description of the drawings]

[0010] [Figure 1] FIG. 1 is a schematic plan view of a bioparticle concentrating device according to a first embodiment of the present invention. [Diagram 2] FIG. 2 is a schematic perspective view showing a part of FIG. [Diagram 3] FIG. 3 is a schematic cross-sectional view taken along line III-III in FIG. 2. [Figure 4] FIG. 4 is a cross-sectional schematic diagram of the second valve of FIG. 3 being switched to a closed mode; [Diagram 5] FIG. 5 is a cross-sectional schematic showing that dielectrophoretic (DEP) forces move bioparticles in FIG. 4. [Figure 6] 6 is a schematic cross-sectional view showing output of a pico droplet by driving the piezoelectric member in FIG. 5. FIG. [Figure 7] FIG. 7 is a cross-sectional schematic diagram of the second valve of FIG. 6 being switched to an open mode. [Figure 8] 4A-4C are schematic cross-sectional views showing another operation process of the bioparticle concentrating device according to the first embodiment of the present invention. [Figure 9] FIG. 9 is a schematic cross-sectional view showing a process continuing from FIG. 8. [Figure 10] FIG. 2 is a schematic perspective view showing a portion of a bioparticle concentrating device according to a second embodiment of the present invention. [Figure 11] FIG. 11 is a schematic cross-sectional view taken along line XI-XI in FIG. [Figure 12] FIG. 12 is an enlarged schematic view of part XII in FIG. [Figure 13] FIG. 13 is a schematic plan view of the vertical transistor of FIG. 12. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] The following is a detailed description of the embodiments of the "bioparticle concentrating apparatus, bioparticle concentrating device, and pico-droplet generating apparatus" disclosed in the present invention, using specific examples. Those skilled in the art can understand the advantages and effects of the present invention from the disclosure of this specification. The present invention can be implemented or applied in other different embodiments. Each detail in this specification can be modified or changed in various ways without departing from the spirit of the present invention, based on various aspects or applications. In addition, the drawings of the present invention are for simple and schematic illustration only, and do not show actual dimensions. The following embodiments will further describe the technical matters related to the present invention, but the disclosed contents do not limit the present invention.

[0012] In addition, although various components or signals may be described in this specification by terms such as "first", "second", "third", etc., these components or signals are not limited by these terms. It should be understood that these terms are mainly used to distinguish one component from another component or one signal from another signal. In addition, the term "or" used in this specification may include any one or more combinations of related items according to actual circumstances.

[0013] [First embodiment] 1 to 9, a first embodiment of the present invention is provided. As shown in Fig. 1 to 3, this embodiment provides a bioparticle concentration device 1000 for separating at least one bioparticle B from bioparticles B in a liquid sample L, thereby allowing the at least one bioparticle B to be collected in a first container 700.

[0014] In this embodiment, the liquid sample L can be a body fluid sample from an animal (e.g., blood, lymph, saliva, ascites, or urine), and the bioparticles B can be specific types of cells, such as circulating tumor cells (CTCs), fetal nucleated red blood cells (FNRBCs), exosomes, viruses, or bacteria, but the invention is not limited thereto. For example, in other embodiments of the invention not shown in the drawings, the liquid sample L can also be obtained from a plant.

[0015] Furthermore, the bioparticle concentration device 1000 in this embodiment includes a pico droplet generating device 100, a power supply device 200 electrically connected to the pico droplet generating device 100, a pressure balance device 300 spatially connected to the internal space of the pico droplet generating device 100, a camera device 400 for observing the pico droplet generating device 100, a control device 500 for driving (or triggering) the pico droplet generating device 100, and a light source mechanism 600 used in cooperation with the pico droplet generating device 100 in a non-contact manner, but the present invention is not limited thereto.

[0016] For example, in other embodiments of the invention not shown in the drawings, the configuration and number of internal components of bioparticle concentration device 1000 may be varied or adjusted according to design requirements (e.g., light source mechanism 600 may be omitted), and pico-droplet generator 100 may be used independently (e.g., sold) or in conjunction with other devices (e.g., pico-droplet generator 100 and light source mechanism 600 may be used in conjunction with each other and jointly defined as a bioparticle concentration device).

[0017] The following description describes the structure and connection relationship of each part of the bioparticle concentrating device 1000, and then describes the connection relationship of each part of the bioparticle concentrating device 1000. It should be noted that the pico droplet generator 100 of this embodiment is formed on a chip scale (e.g., the thickness of the pico droplet generator 100 is in the range of 600 μm to 800 μm), and the pico droplet generator 100 shown in the drawings has a rectangular structure, but the present invention is not limited thereto. For example, in other embodiments of the present invention not shown in the drawings, the pico droplet generator 100 can have a curved structure or an irregular structure.

[0018] Specifically, the pico droplet generating device 100 of this embodiment is located away from the optical sensing structure 1. Opposing structure 2, along the thickness direction D1, the optical sensing structure 1 and Opposing structure 2, a bonding layer 3 disposed between the bonding layer 3 and a piezoelectric member 4 disposed on the bonding layer 3. Opposing structure 2 is transparent. According to actual requirements, Opposing structure At least one of 2 and the optical sensing structure 1 may be transparent, allowing the pico-droplet generator 100 to operate properly.

[0019] The light-sensing structure 1 includes a first substrate 11, a first electrode layer 12 formed on one side (e.g., bottom side) of the first substrate 11, a photovoltaic layer 13 formed on another side (e.g., top side) of the first substrate 11, and an insulating layer 14 covering at least a part of the photovoltaic layer 13. In this embodiment, the first substrate 11 is a silicon substrate, preferably a low-concentration N-type layer. The first electrode layer 12 can cover the entire bottom side of the first substrate 11, and the first electrode layer 12 is preferably a thin conductive metal layer or an indium tin oxide (ITO) layer. Furthermore, the configuration or layout of the photovoltaic layer 13 can be adjusted or changed according to design requirements, and the present invention is not limited thereto. For example, the photovoltaic layer 13 can have multiple vertical transistors in a matrix-like arrangement, and the detailed features of the vertical transistors of the photovoltaic layer 13 are described in the following second embodiment for brevity.

[0020] Opposing structure 2 includes a second substrate 21 and a second electrode layer 22 formed on the second substrate 21 and facing the light-sensing structure 1. The bonding layer 3 is a bonding layer between the light-sensing structure 1 and Opposing structure 2, thereby jointly defining a sorting channel 5 along a flow direction D2 perpendicular to the thickness direction D1.

[0021] in particular, Opposing structure At least one of the bonding layer 2 and the bonding layer 3 has an inlet 31 and an outlet 32, which are spatially connected to two ends of the sorting channel 5, respectively. In other words, the inlet 31 is located upstream of the sorting channel 5, and the outlet 32 ​​is located downstream of the sorting channel 5. Furthermore, the inlet 31 and the outlet 32 ​​in this embodiment are formed in the bonding layer 3, and in the pico droplet generating device 100, the liquid sample L can be injected into the pico droplet generating device 100 through the inlet 31 and can flow out of the pico droplet generating device 100 through the outlet 32.

[0022] Furthermore, the bonding layer 3 has sorting holes 33 that are in spatial communication with the sorting channel 5 along an outflow direction D3 (through) perpendicular to the thickness direction D1 and the flow direction D2. In this embodiment, the picodroplet generator 100 preferably has a hydrophobic surface 34 surrounding the sorting holes 33. That is, the sorting holes 33 are defined by being surrounded by the hydrophobic surface 34. The hydrophobic surface 34 in this embodiment is formed by the bottom edge portions of the bonding layer 3 located on two opposing sides of the sorting holes 33 along the flow direction D2. (For example, FIG. 3 ), the optical sensing structure 1 and the optical sensing structure 2 are located on two opposite sides of the sorting hole 33 along the thickness direction D1, respectively. Opposing structure 2 and an outer surface (not shown) of the bonding layer 3. Furthermore, the sorting hole 33 is disposed substantially in the center of the bonding layer 3 along the flow direction D2, the width W33 of the sorting hole 33 along the flow direction D2 is within a range of 40 μm to 300 μm, and the outflow direction D3 is substantially perpendicular to a horizontal plane or substantially parallel to a vertical line, but the present invention is not limited thereto.

[0023] The piezoelectric member 4 is disposed outside the bonding layer 3 and located outside the sorting channel 5, and the piezoelectric member 4 and the sorting hole 33 are located on two opposing sides of the bonding layer 3 along the outflow direction D3. The pico droplet generating device 100 has a pico droplet emission region R defined by extending from the sorting hole 33 toward the piezoelectric member 4.

[0024] In this embodiment, the pico droplet emission region R is disposed in a projection region defined by projecting the sorting hole 33 perpendicularly onto the piezoelectric member 4 along the outflow direction D3, and the boundary of the pico droplet emission region R is a distance in the range of 50 μm to 200 μm away from the center of the sorting hole 33 along the outflow direction D3. In other words, the pico droplet emission region R can cover the entire width W5 of the sorting channel 5 along the outflow direction D3, and the volume covered by the pico droplet emission region R can be substantially equal to at least one pico droplet L1 depending on design requirements.

[0025] In addition, the specific scope of the pico droplet emission region R can be changed or adjusted according to design requirements and is not limited by the drawings. For example, in other embodiments of the present invention not shown in the drawings, the pico droplet emission region R can be a fan shape extending from the sorting hole 3. Or, the pico droplet emission region R can cover a portion of the width W5 of the sorting channel 5 along the outflow direction D3 (for example, the pico droplet emission region R in the outflow direction D3 occupies only 30% to 80% of the width W5 of the sorting channel 5).

[0026] In this embodiment, power supply 200 is an alternating current (AC) power supply. Power supply 200 is electrically coupled to first electrode layer 12 and second electrode layer 22 of pico droplet generator 100 and provides electricity for the cooperative operation of pico droplet generator 100 and light source mechanism 600.

[0027] The pressure balancing device 300 includes a first valve 301 assembled to the inlet 31 and a second valve 302 assembled to the outlet 32. The pressure balancing device 300 is configured to control the velocity and pressure of the liquid sample L in the sorting channel 5 through the first valve 301 and the second valve 302. For example, the pressure balancing device 300 enables the liquid sample L to form a liquid level L2 in the sorting hole 33 such that it is flush with the outer surface (e.g., bottom edge) of the bonding layer 3.

[0028] In particular, the pressure balance device 300 in this embodiment includes an air pump 303, a switch 304 connected to the air pump 303, a pressure balance bottle 305 in fluid communication with the air pump 303 and the switch 304, a liquid inlet bottle 306 in fluid communication with the switch 304 and the first valve 301, and a second container 307 in fluid communication with the second valve 302. The liquid inlet bottle 306 allows a liquid sample L received therein to be inject into the sorting channel 5 through the first valve 301 and the inlet 31. The second container 307 is provided to receive the sorted liquid sample L that flows out of the outlet 32 ​​and the second valve 302.

[0029] The camera device 400 is positioned in correspondence with the viewable segment 51 of the sorting channel 5, and the camera device 400 is preferably configured to capture real-time images of the liquid sample L within the viewable segment 51, thereby allowing a preferred operation time of the pico-droplet generator 100 to be determined. It should be noted that the bioparticles B located within the viewable segment 51 can be separated into at least one target bioparticle B1 and at least one non-target bioparticle B2. Also, the camera device 400 is preferably configured to capture real-time images of the liquid sample L within the viewable segment 51, such that a preferred operation time of the pico-droplet generator 100 can ... Opposing structure 2, which allows a clear observation of the actual state of the liquid sample L flowing in the sorting channel 5 along the flow direction D2.

[0030] Specifically, the boundaries of the visible segment 51 are spaced apart from the centers of the sorting holes 33 along the flow direction D2 at a distance in the range of 100 μm to 300 μm, the visible segment 51 covers the entire width W5 of the sorting channel 5 along the outflow direction D3, and the pico droplet emission region R is located in the visible segment 51. In other words, the visible segment 51 can be defined as a filtered segment, a portion of the sorting channel 5 located upstream of the visible segment 51 can be defined as an unfiltered segment, and another portion of the sorting channel 5 located downstream of the visible segment 51 can be defined as an unfiltered segment, although the invention is not limited thereto.

[0031] The controller 500 is electrically coupled to the piezoelectric member 4 of the pico-droplet generator 100, and the controller 500 can be used to selectively trigger (or drive) the piezoelectric member 4 in conjunction with real-time images captured by the camera arrangement 400. It should be noted that when the piezoelectric member 4 (or the light source mechanism 600) is operating, the pressure balance arrangement 300 maintains the pressure of the liquid sample L in the sorting channel 5 with the first valve 301 in an open mode and the second valve 302 in a closed mode (as shown in Figures 4 to 6).

[0032] As shown in Figures 1, 5, and 6, when the real-time image acquired by the camera device 400 detects that a bioparticle B (e.g., at least one target bioparticle B1) is positioned in the pico droplet emission region R, the control device 500 tricks the piezoelectric member 4 (e.g., vibrates the piezoelectric member 4 to generate sound waves) to drive the liquid sample L within the pico droplet emission region R and pass through the sorting hole 33 to form a pico droplet L1 encapsulating at least one of the bioparticles B (e.g., at least one target bioparticle B1), which is received (or collected) in the first container 700.

[0033] Additionally, when a bioparticle B (e.g., at least one target bioparticle B1) is located away from the sorting hole 33, the control device 500 continuously tricks the piezoelectric member 4 to output multiple pico droplets L1, ensuring that at least one of the pico droplets L1 output from the pico droplet generating device 100 encapsulates a bioparticle B (e.g., at least one target bioparticle B1).

[0034] Therefore, the configuration of the pico droplet generator 100 of the bioparticle concentrating device 1000 provided in this embodiment can be used to quickly and accurately perform the sorting and concentrating process of bioparticles B (e.g., at least one target bioparticle B1) through the piezoelectric member 4. The pico droplet generator 100 of this embodiment has a configuration that allows for mass production, thereby facilitating a reduction in the overall cost of the bioparticle concentrating device 1000.

[0035] In addition, in order for the pico droplet generating device 100 to accurately form a pico droplet L1 enveloping at least one target bio particle B1 and effectively carry out the concentration process of the target bio particle B1, the pico droplet generating device 100 is preferably used in cooperation with a light source mechanism 600. As shown in FIG. 2, FIG. 4, and FIG. 5, the light source mechanism 600 is disposed next to the camera device 400, and the light source mechanism 600 is configured to irradiate light onto at least one target bio particle B1 to move at least one target bio particle B1 to the pico droplet emission region R so as to apply a dielectrophoretic (DEP) force F1 to the at least one target bio particle B1 through the optical sensing structure 1. Furthermore, the light source mechanism 600 can be used to irradiate light onto at least one non-target bio particle B2 to apply a dielectrophoretic (DEP) force F2 to at least one non-target bio particle B2 through the optical sensing structure 1 so as to move at least one non-target bio particle B2 away from the pico droplet emission region R.

[0036] In this manner, the pico droplet generating device 100 and the light source mechanism 600 of the bioparticle concentration device 1000 provided in this embodiment can be used in cooperation with each other to quickly and accurately ensure that the pico droplet emission area R has only at least one target bioparticle B1, so that at least one target bioparticle B1 can be collected in the first container 700 by forming a pico droplet L1.

[0037] 1 and 7, after at least one target bioparticle B1 in the picodroplet emission region R is collected in the first container 700, the second valve 302 can be opened again to allow the liquid sample L in the visible segment 51 that does not contain the target bioparticle B1 to flow into the second container 307. This allows the non-target bioparticles B2 to be collected in the second container 307, but the present invention is not limited thereto.

[0038] 1, 8 and 9, the light source mechanism 600 can be configured to irradiate at least one target bio particle B1 with light, thereby moving the at least one target bio particle B1 away from the pico droplet emission region R, and to irradiate at least one non-target bio particle B2 with light, thereby moving the at least one non-target bio particle B2 toward the pico droplet emission region R. As a result, the at least one non-target bio particle B2 is collected in the first container 700 by forming a pico droplet L1, and the at least one target bio particle B1 is collected in the second container 307.

[0039] Also, in this embodiment, the pico droplet generating device 100 has only one sorting hole 33, but the present invention is not limited thereto. For example, in another embodiment of the present invention not shown, the pico droplet generating device 100 may have a plurality of sorting holes 33 arranged along the flow direction D2 and spaced apart from each other. In this way, a plurality of types of different bioparticles B can be sorted through the plurality of sorting holes 33.

[0040] [Second embodiment] 10 to 13, a second embodiment of the present invention is provided, which is similar to the first embodiment of the present invention. For the sake of brevity, the description of the same components of the first and second embodiments of the present invention is omitted here, and the following description only discloses the different features between the first and second embodiments.

[0041] In this embodiment, the photovoltaic layer 13 can generate a better photoelectric coupling effect through a specific configuration. Specifically, the photovoltaic layer 13 includes a collector layer 131 formed on the first substrate 11, a plurality of base regions 1321 formed in the collector layer 131, and a plurality of emitter regions 1331 each formed in the base region 1321. In other words, the collector layer 131 is an N-type layer, and the plurality of base regions 1321 are located at the same height relative to the first electrode layer 12 and are jointly defined as a base layer 132 which is a P-type layer. The plurality of emitter regions 1331 are located at the same height relative to the first electrode layer 12 and are jointly defined as an emitter layer 133 which is a high concentration N-type layer.

[0042] Specifically, the collector layer 131 in this embodiment includes a connection layer 1311 formed on the first substrate 11, and a plurality of collector regions 1312 formed on the connection layer 1311 and spaced apart from each other. One end (e.g., the upper end) of each of the collector regions 1312 is spaced apart from the first electrode layer 12 and has a first slot-shaped portion 1313.

[0043] It should be noted that the multiple collector regions 1312 in this embodiment are electrically coupled to each other through the connection layer 1311, but the present invention is not limited thereto. For example, in other embodiments of the present invention not shown, according to design requirements, the collector layer 131 is provided without the connection layer 1311, and the multiple collector regions 1312 can be directly formed on the first substrate 11, and the first substrate 11 can be a low-doped N-type layer, so that the first substrate 11 and the collector layer 131 can jointly be used as a collector.

[0044] The multiple base regions 1321 are respectively formed in first slot-shaped portions 1313 of the multiple collector regions 1312 (i.e., each of the collector regions 1312 is formed with one of the base regions 1321 disposed therein), and one end (e.g., the upper end) of each of the base regions 1321 is spaced apart from the first electrode layer 12 and has multiple second slot-shaped portions 1322 spaced apart from each other.

[0045] Also, a plurality of emitter regions 1331 are formed within each of the base regions 1321 (i.e., each of the base regions 1321 is formed with one of the emitter regions 1331 disposed therein). Each of the emitter regions 1331 includes a plurality of emitter pads 1332 formed within a respective one of the plurality of second slot-shaped portions 1322 of the corresponding one of the base regions 1321.

[0046] In short, each of the base regions 1321, the corresponding collector regions 1312, and the corresponding emitter regions 1331 are jointly formed as a vertical transistor 130. The insulating layer 14 in this embodiment is a silicon nitride layer or a silicon oxide layer, but the present invention is not limited thereto. The insulating layer 14 covers the vertical transistors 130 and separates the vertical transistors 130 from each other, and one end (e.g., the upper end) of each of the emitter pads 1332 is separated from the first electrode layer 12 and exposed from the insulating layer 14. In other words, the insulating layer 14 is covered and connected to the connecting layer 1311 and the peripheral side surfaces of each of the vertical transistors 130.

[0047] It should be noted that the vertical transistors 130 in this embodiment have substantially the same structure, so the following description discloses only one structure of the vertical transistors 130 for the sake of brevity, but the present invention is not limited thereto. For example, in other embodiments of the present invention not shown, the vertical transistors 130 may have different structures.

[0048] In this embodiment, the one end of the collector region 1312, the one end of the base region 1321, and the one end of each of the emitter pads 1332 are preferably coplanar with each other. Each emitter pad 1332 has a width greater than its thickness. The distance between two adjacent emitter pads 1332 is less than 5 μm, but the present invention is not limited thereto. Also, the thickness of the base region 1321 is within a range of 15% to 35% of the thickness of any of the collector regions 1312, and the thickness of any of the emitter pads 1332 is within a range of 5% to 20% of the thickness of the base region 1321, but the present invention is not limited thereto.

[0049] It should also be noted that from the perspective of bioparticles, small modifications to pico-droplet generator 100 can have a large effect thereon. Thus, while the above description describes the size and placement of emitter pad 1332 of vertical transistor 130 to facilitate sorting of bioparticles by gradually distributing the electric field difference, the present invention is not limited thereto.

[0050] In this embodiment of the vertical transistor 130, the multiple emitter pads 1332 include a first pad 1332a arranged along the inner ring-shaped path P1, a center pad 1332d arranged inside the inner ring-shaped path P1, a second pad 1332b arranged along the outer ring-shaped path P2, and a third pad 1332c arranged along the additional ring-shaped path P3. The outer ring-shaped path P2 surrounds the inner ring-shaped path P1, and the additional ring-shaped path P3 is located between the inner ring-shaped path P1 and the outer ring-shaped path P2, but the present invention is not limited thereto. For example, in other embodiments of the present invention not shown, the center pad 1332d and / or the third pad 1332c can be omitted according to design requirements. Also, the number of the additional ring-shaped paths P3 between the inner ring-shaped path P1 and the outer ring-shaped path P2 can be at least two.

[0051] Specifically, the width of the central pad 1332d, the width of the first pad 1332a, and the width of the second pad 1332b are different from each other, and the width of the third pad 1332c is within the range of the width of the first pad 1332a and the width of the second pad 1332b. In this embodiment, it is preferable that the width of the plurality of emitter pads 1332 gradually decreases from the outer ring-shaped path P2 to the central pad 1332d. In other words, the plurality of emitter pads 1332 are listed in the order of the width from the largest to the smallest, that is, the second pad 1332b, the third pad 1332c, the first pad 1332a, and the central pad 1332d, but the present invention is not limited thereto.

[0052] In addition, although an example has been given in which the specific distribution, quantity, and shape of the first pad 1332a, the second pad 1332b, and the third pad 1332c are configured as a single square ring, the specific distribution, quantity, and shape of the first pad 1332a, the second pad 1332b, and the third pad 1332c can be adjusted or changed according to design requirements.

[0053] In summary, any one of the vertical transistors 130 is configured to be illuminated by the light source mechanism 600, and the distribution of the multiple emitter pads 1332 and the electric field differences generated within the liquid sample from the non-uniform electric fields of the emitter pads 1332 result in the application of multiple dielectrophoretic (DEP) forces to move bioparticles (e.g., at least one target bioparticle).

[0054] Therefore, the photoelectric layer 13 of the bioparticle concentrating device 1000 provided in this embodiment has a specific structural design, so that the emitter pad 1332 of any one of the vertical phototransistors 130 can be used in a non-contact photoelectric coupling manner to jointly generate an electric field that forms an electric field difference similar to corona discharge, thereby allowing the emitter pad 1332 of any one of the vertical phototransistors 130 to accurately move (or catch) at least one target bioparticle to any position.

[0055] [Beneficial Effects of the Embodiments of the Invention] In conclusion, the pico-droplet generator configuration of the bioparticle concentrator provided by the present invention can be used to rapidly and accurately perform a sorting and concentration process of a bioparticle (or at least one target bioparticle) through a piezoelectric member. The pico-droplet generator of the present invention is provided in a mass-producible configuration, which facilitates reducing the overall cost of the bioparticle concentrator.

[0056] In addition, the pico-droplet generating device and the light source mechanism of the bio-particle concentrating device provided by the present invention can be used in cooperation with each other to quickly and accurately ensure that the pico-droplet emitting area has at least one target bio-particle therein, so that the at least one target bio-particle is collected by forming a pico-droplet.

[0057] The contents disclosed above are merely preferred possible embodiments of the present invention, and do not limit the scope of the claims of the present invention. Therefore, all equivalent technical modifications made based on the contents of the specification and accompanying drawings of the present invention are intended to be included in the scope of the claims of the present invention. [Explanation of symbols]

[0058] 1000: Bioparticle Concentration Device 100: Pico Droplet Generator 1: Optical sensing structure 11: First substrate 12: First electrode layer 13: Photoelectric layer 130: Vertical transistor 131: Collector layer 1311: Connection layer 1312 : Collector area 1313: First slot-shaped section 132: Base layer 1321: Base area 1322: Second slot-like section 133: Emitter layer 1331: Emitter area 1332: Emitter pad 1332a: First pad 1332b: Second Pad 1332c : Third Pad 1332d: Center pad 14: Insulating layer 2: Opposing structure 21: Second board 22: Second electrode layer 3: Bonding layer 31: Inlet 32: Outlet 33: Sorting hole 34 : Hydrophobic surface 4: Piezoelectric material 5: Selection channel 51: Visible segment 200: Power supply 300: Pressure balance device 301: First valve 302: Second valve 303: Air pump 304: Switch 305: Pressure balance bottle 306: Liquid injection bottle 307: Second Container 400: Camera equipment 500: Control device 600: Light source mechanism 700: First container L: Liquid sample L1: Picodroplet L2: Liquid level B: Bioparticles B1: Target biological particles B2: Non-targeted bioparticles D1: Thickness direction D2: Flow direction D3: Drop direction W5, W33: Width R: Picodroplet emission area F1, F2: Dielectrophoretic (DEP) forces P1: Inner ring path P2: Outer ring path P3: Additional ring route

Claims

1. A bioparticle concentration device provided for separating at least one bioparticle from a liquid sample containing the bioparticles, comprising: The bioparticle concentration device includes a pico-droplet generator, a power supply, a pressure balancer, a camera, and a control device; The picodroplet generator includes an optical sensing structure, a facing structure, a bonding layer, and a piezoelectric member; The optical sensing structure includes a first substrate, a first electrode layer and a photoelectric layer formed on both sides of the first substrate, respectively, and an insulating layer covering the photoelectric layer; the opposing structure is spaced apart from the light sensing structure, and at least one of the opposing structure and the light sensing structure is transparent; the facing structure includes a second substrate and a second electrode layer formed on the second substrate and facing toward the light-sensing structure; the bonding layer is connected between the optical sensing structure and the opposing structure along a thickness direction, thereby jointly defining a sorting channel together with the optical sensing structure and the opposing structure along a flow direction perpendicular to the thickness direction; At least one of the facing structure and the bonding layer has an inlet located upstream of the sorting channel and an outlet located downstream of the sorting channel; the bonding layer has sorting holes that are spatially connected to the sorting channels along an outflow direction perpendicular to the thickness direction and the flow direction; the piezoelectric member is disposed on the bonding layer, the piezoelectric member and the sorting hole are disposed on two opposing sides of the bonding layer along the bleeding direction, and the pico droplet generating device has a pico droplet emission area defined by extending from the sorting hole toward the piezoelectric member; the power supply is electrically coupled to the first electrode layer and the second electrode layer; the pressure balancing device includes a first valve assembled to the inlet and a second valve assembled to the outlet, the pressure balancing device being configured to control a velocity and a pressure of a liquid sample in the sorting channel via the first valve and the second valve; the camera device is positioned in correspondence with a viewable segment of the sorting channel and configured to capture real-time images of the liquid sample within the viewable segment; The controller is electrically coupled to the piezoelectric member, and when the real-time image captured by the camera device shows at least one bioparticle located within the picodroplet emission area, the controller triggers the piezoelectric member to output the liquid sample within the picodroplet emission area through the sorting hole to form a picodroplet with the bioparticle covered therein. A bioparticle concentrating device comprising:

2. the bioparticles located within the visible segment include at least one target bioparticle; 2. The bioparticle concentration device of claim 1, further comprising a light source mechanism configured to irradiate light onto at least one of the target bioparticles located within the visible segment, to apply a dielectrophoretic (DEP) force to the at least one of the target bioparticles through the optical sensing structure, and to move the at least one of the target bioparticles to a picodroplet emission region.

3. 3. The bioparticle concentration device of claim 2, wherein the bioparticles located within the visible segment include at least one non-target bioparticle, and the light source mechanism is configured to irradiate light onto the at least one non-target bioparticle and apply a dielectrophoretic (DEP) force to the at least one non-target bioparticle through the light sensing structure to move the at least one non-target bioparticle away from the picodroplet emission region.

4. The photovoltaic layer, a collector layer, a plurality of base regions, and a plurality of emitter regions, the collector layer is formed on the first substrate, the collector layer having a plurality of collector regions spaced apart from one another, each collector region having a first slot-like portion at one end remote from the first electrode layer; the plurality of base regions are respectively formed within the first slot-shaped portion of the collector region, and each base region has a plurality of second slot-shaped portions at one end thereof remote from the first electrode layer and spaced apart from each other; the plurality of emitter regions are formed corresponding to the base region, each of the emitter regions has a plurality of emitter pads formed in the plurality of second slot-shaped portions of the corresponding base region, any one of the base regions, the collector region corresponding thereto, and the emitter region corresponding thereto are jointly formed as a vertical transistor, the insulating layer covers the vertical transistors so as to separate them, and one end of each of the emitter pads remote from the first electrode layer is exposed from the insulating layer, 3. The bioparticle concentration device of claim 2, wherein any of the vertical transistors are configured to be illuminated by a light source mechanism to generate non-uniform electric fields through a distribution of the emitter pads, thereby exerting dielectrophoretic (DEP) forces on at least one of the target bioparticles.

5. 5. The bioparticle concentration device of claim 4, wherein in each of the vertical transistors, the plurality of emitter pads include a first pad arranged along an inner ring-shaped path and a second pad arranged along an outer ring-shaped path surrounding the inner ring-shaped path, and a width of the first pad is different from a width of the second pad.

6. 6. The bioparticle concentration device of claim 5, wherein in each of the vertical transistors, the plurality of emitter pads include a third pad arranged along an additional ring path located between the inner ring path and the outer ring path, and a width of the third pad is within a range between a width of the first pad and a width of the second pad.

7. 3. The bioparticle concentrating device of claim 2, wherein when the piezoelectric member or the light source mechanism is operated, the pressure balance device maintains the pressure of the liquid sample in the sorting channel by placing the first valve in an open mode and the second valve in a closed mode.

8. 2. The bioparticle concentration device of claim 1, wherein the pico-droplet generating device has a hydrophobic surface surrounding the sorting hole, and the pressure balancing device forms a liquid surface within the sorting hole where the liquid sample is flush with the outer surface of the bonding layer.

9. the bio-particle concentrating device comprises a first container for receiving the pico-droplets; The pressure balance device is An air pump and A switch connected to the air pump; a pressure balance bottle in fluid communication with the air pump and the switch; a liquid inlet bottle in fluid communication with the switch and the first valve, for injecting the liquid sample received therein through the first valve and the inlet into the sorting channel; a second container in fluid communication with the second valve. The bioparticle concentrating device of claim 8.

10. 2. The bioparticle concentrating device of claim 1, wherein the width of the sorting hole is in the range of 40 μm to 300 μm along the flow direction, and the boundary of the visible segment is separated from the center of the sorting hole along the flow direction by a distance in the range of 100 μm to 300 μm.

11. The bioparticle concentrating device according to claim 10 , wherein the picodroplet emission region is disposed in a projection region defined by projecting the sorting hole onto the piezoelectric member along the outflow direction.

12. 11. The bioparticle concentrating device of claim 10, wherein a boundary of the picodroplet emission region is spaced from a center of the sorting hole along the exit direction by a distance in the range of 50 μm to 200 μm.

13. A bioparticle concentration device for selecting target bioparticles from a liquid sample containing a plurality of bioparticles, comprising: The bioparticle concentrating device includes a pico-droplet generating device and a light source mechanism; The picodroplet generator includes an optical sensing structure, a facing structure, a bonding layer, and a piezoelectric member; The optical sensing structure includes a first substrate, a first electrode layer and a photoelectric layer formed on two opposing sides of the first substrate, respectively, and an insulating layer covering the photoelectric layer; the facing structure is disposed at a distance from the light sensing structure, and at least one of the facing structure and the light sensing structure is transparent, the facing structure including a second substrate and a second electrode layer formed on the second substrate and facing towards the light sensing structure; the bonding layer is connected between the optical sensing structure and the opposing structure along a thickness direction, thereby jointly defining a sorting channel together with the optical sensing structure and the opposing structure along a flow direction perpendicular to the thickness direction, at least one of the opposing structure and the bonding layer having an inlet located upstream of the sorting channel and an outlet located downstream of the sorting channel, the bonding layer having a sorting hole spatially communicating with the sorting channel along an outflow direction perpendicular to the thickness direction and the flow direction; the piezoelectric member is disposed on the bonding layer, the piezoelectric member and the sorting hole are disposed on two opposite sides of the bonding layer along the bleeding direction, and the pico droplet generator has a pico droplet emission area defined by extending from the sorting hole toward the piezoelectric member; The light source mechanism is configured to irradiate light to the target bioparticle in the pico-droplet generating device to apply a dielectrophoretic (DEP) force to the target bioparticle through the light sensing structure, thereby moving the target bioparticle to a pico-droplet emission region, and the piezoelectric member drives the liquid sample in the pico-droplet emission region to output through the sorting hole, forming a pico-droplet in which the target bioparticle is covered. A bioparticle concentrating device comprising:

14. 1. A pico-droplet generator comprising an optical sensing structure, a facing structure, a bonding layer, and a piezoelectric member, The optical sensing structure includes a first substrate, a first electrode layer and a photoelectric layer formed on two opposing sides of the first substrate, respectively, and an insulating layer covering the photoelectric layer; the facing structure is disposed at a distance from the light sensing structure, at least one of the facing structure and the light sensing structure is transparent, the facing structure includes a second substrate and a second electrode layer formed on the second substrate and facing toward the light sensing structure; the bonding layer is connected between the optical sensing structure and the counter structure along a thickness direction and jointly defines a sorting channel together with the optical sensing structure and the counter structure along a flow direction perpendicular to the thickness direction, at least one of the counter structure and the bonding layer has an inlet located upstream of the sorting channel and an outlet located downstream of the sorting channel, the bonding layer has a sorting hole spatially communicating with the sorting channel along an outlet direction perpendicular to the thickness direction and the flow direction; the piezoelectric member is disposed on the bonding layer, the piezoelectric member and the sorting hole are disposed on two opposite sides of the bonding layer along the bleeding direction, respectively, and the pico droplet generator has a pico droplet emission area defined by extending from the sorting hole toward the piezoelectric member. A pico droplet generating device.

15. The pico droplet generating device of claim 14, wherein the pico droplet generating device has a hydrophobic surface surrounding the sorting hole, the width of the sorting hole is in the range of 40 μm to 300 μm along the flow direction, the pico droplet emission area is disposed in a projection area defined by projecting the sorting hole onto the piezoelectric member along the outflow direction, and the boundary of the pico droplet emission area is separated from the center of the sorting hole by a distance in the range of 50 μm to 200 μm along the outflow direction.

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