CN116496889A - Non-contact sorting device, light triggering structure thereof and biological particle sorting equipment - Google Patents
Non-contact sorting device, light triggering structure thereof and biological particle sorting equipment Download PDFInfo
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Abstract
The invention discloses a non-contact sorting device, a light triggering structure thereof and biological particle sorting equipment. The light triggering structure comprises a first substrate, a first electrode layer formed on the first substrate, a photodiode layer formed on the first electrode layer and an insulating layer covering the photodiode layer. The thickness of the photodiode layer is 1-3 microns and comprises a first doping layer, an I-type layer and a second doping layer which are stacked in sequence from the first electrode layer. The second doped layer comprises a plurality of trigger pads arranged at intervals, each trigger pad has a width ranging from 3 micrometers to 7 micrometers, and a distance of not more than 2 micrometers is arranged between any two adjacent trigger pads. Accordingly, the photodiode layer has a specific structural design, so that a relatively concentrated electric field can be generated in a photoelectric coupling mode, and the target biological particles can be accurately moved to any region.
Description
Technical Field
The invention relates to a sorting device, in particular to a non-contact sorting device, a light triggering structure thereof and biological particle sorting equipment.
Background
Existing biological particle sorting devices can drive the movement of target biological particles by applying an electric field. However, how to move the target biological particles along a predetermined route more accurately without contacting the target biological particles, which is a direction in which the existing biological particle sorting apparatus needs to be further improved and refined.
Accordingly, the present inventors considered that the above-mentioned drawbacks could be improved, and have intensively studied and combined with the application of scientific principles, and finally have proposed an invention which is reasonable in design and effectively improves the above-mentioned drawbacks.
Disclosure of Invention
The embodiment of the invention provides a non-contact type sorting device, a light triggering structure thereof and biological particle sorting equipment, which are used for solving the possible defects of the existing biological particle sorting device.
To solve the above-mentioned problems, an embodiment of the present invention discloses a biological particle sorting apparatus for sorting a target biological particle from a liquid sample, the biological particle sorting apparatus comprising: a non-contact sorting device and an AC power supply device;
The non-contact sorting device comprises: an optical triggering structure, comprising: a first substrate; a first electrode layer formed on the first substrate; a photodiode layer formed on the first electrode layer and having a thickness of 1-3 micrometers (μm); wherein, photodiode layer includes: a first doped layer formed on the first electrode layer; an I-type layer formed on the first doped layer; and a second doped layer comprising a plurality of trigger pads formed on the I-type layer and spaced apart from each other; wherein each trigger pad has a width of 3-7 microns, and a distance of not more than 2 microns is provided between any two adjacent trigger pads; an insulating layer covering the photodiode layer;
the matching structure is arranged at intervals with the light triggering structure, at least one of the matching structure is transparent, the matching structure comprises a second substrate and a second electrode layer formed on the second substrate, and the second electrode layer faces the light triggering structure;
the alternating current power supply device is electrically coupled with the first electrode layer and the second electrode layer;
when the liquid sample is located between the insulating layer and the second electrode layer of the non-contact sorting device, the non-contact sorting device is used for enabling a light source to irradiate on at least one trigger pad, so that the non-contact sorting device generates a concentrated and non-uniform electric field at the liquid sample, and a dielectrophoresis force capable of driving the target biological particles to move is applied to the target biological particles.
Preferably, the biological particle sorting apparatus as described above, wherein the photodiode layer further includes a plurality of transparent electrode pads formed on the plurality of trigger pads, respectively, and a width of each trigger pad is greater than a width of the corresponding transparent electrode pad.
Preferably, the biological particle sorting apparatus as described above, wherein the thickness of each trigger pad is 3% -10% of the thickness of the corresponding transparent electrode pad.
Preferably, the biological particle sorting apparatus as described above, wherein the first doped layer covers at least 90% of the area of the first electrode layer, and the I-type layer covers the entire first doped layer.
Preferably, the biological particle sorting apparatus as described above, wherein the I-type layer is concavely provided with a patterned groove such that the I-type layer constitutes a plurality of bosses arranged at intervals, and a plurality of trigger pads are respectively formed on the plurality of bosses.
Preferably, the biological particle sorting apparatus as described above, wherein the edge of each trigger pad is aligned with the edge of the corresponding land, and the depth of the patterned trench is 1% -5% of the thickness of the I-layer.
Preferably, the biological particle sorting apparatus as described above, wherein the I-shaped layer includes a plurality of I-shaped pads disposed on the first doping layer at intervals, and a plurality of trigger pads are respectively formed on the plurality of I-shaped pads, and each of the trigger pads has a width smaller than a width of a corresponding I-shaped pad.
Preferably, the biological particle sorting apparatus as described above, wherein the first doping layer includes a plurality of spacers disposed on the first electrode layer at intervals, and a plurality of I-shaped pads are formed on the plurality of spacers, respectively, and an edge of each I-shaped pad is aligned with an edge of a corresponding spacer.
Preferably, the biological particle sorting apparatus as described above, wherein the thickness of each trigger pad and the thickness of the first doped layer are respectively 1% to 5% of the thickness of the I-type layer, and the thickness of each trigger pad is smaller than the thickness of the first doped layer.
Preferably, the biological particle sorting apparatus as described above, wherein the non-contact sorting device further comprises:
the bonding layer is connected between the light triggering structure and the matching structure to jointly enclose and define an accommodating space, and the photodiode layer is correspondingly positioned in the accommodating space; a kind of electronic device with high-pressure air-conditioning system
The partition walls are positioned in the accommodating space and are connected with the light triggering structure and the matching structure; wherein, a plurality of partition walls are arranged in a row at intervals, a culture area is formed between any two adjacent partition walls, one side of the row of partition walls is provided with a first flow passage communicated with each culture area, and the other side of the row of partition walls is provided with a second flow passage communicated with each culture area;
When the first flow channel is filled with the liquid sample, the non-contact sorting device can drive the target biological particles to move to a culture area by moving the light source and is restrained by the light source so as not to move to the second flow channel.
Preferably, the biological particle sorting apparatus as described above, wherein the plurality of trigger pads are partially embedded in a plurality of partition walls, each partition wall comprising:
a separator segment;
two first guide sections connected to one end of the partition board section and with one first included angle of 110-160 deg between the partition board section and the first guide section; a kind of electronic device with high-pressure air-conditioning system
Two second guide sections connected to the other end of the partition board section, and each second guide section and the partition board section form a second included angle of 100-160 degrees;
among any two adjacent partition walls, two first guide sections adjacent to each other and respectively belonging to different partition walls jointly define a first opening, and two second guide sections adjacent to each other and respectively belonging to different partition walls jointly define a second opening, wherein the first opening is larger than the second opening.
Preferably, the biological particle sorting apparatus as described above, wherein the first flow channel defines a first flow direction; among the two first guide sections defining any one of the first openings, one first guide section located upstream of the first flow direction has a length longer than that of the other first guide section and is used for contacting the liquid sample along the first flow direction at an acute angle of 70-20 degrees.
Preferably, the biological particle sorting apparatus as described above, wherein each of the culture areas has a first opening communicating with the first flow path and a second opening communicating with the second flow path, and the first opening is larger than the second opening; in the accommodating space of the non-contact sorting device, the first runner can only be communicated with the second runner through any one of the culture areas.
Preferably, the biological particle sorting apparatus as described above, wherein a layout section is formed in at least one of any two adjacent partition walls in the corresponding culture area for extending a path of the liquid sample flowing from the first opening to the second opening.
The embodiment of the invention also discloses a non-contact sorting device for sorting target biological particles from a liquid sample, which comprises: a light triggering structure and a matching structure;
the light triggering structure comprises:
a first substrate;
a first electrode layer formed on the first substrate;
a photodiode layer formed on the first electrode layer and having a thickness of 1-3 μm; wherein, photodiode layer includes: a first doped layer formed on the first electrode layer; an I-type layer formed on the first doped layer; and a second doped layer comprising a plurality of trigger pads formed on the I-type layer and spaced apart from each other; wherein each trigger pad has a width of 3-7 microns, and a distance of not more than 2 microns is provided between any two adjacent trigger pads; and an insulating layer covering the photodiode layer;
The matching structure and the light triggering structure are arranged at intervals, at least one of the matching structure and the light triggering structure is transparent, the matching structure comprises a second substrate and a second electrode layer formed on the second substrate, and the second electrode layer faces the light triggering structure; wherein, the insulation layer and the second electrode layer of the non-contact sorting device can be used for accommodating liquid samples so as to perform a sorting operation corresponding to the target biological particles.
Preferably, in the non-contact sorting apparatus as described above, the photodiode layer further includes a plurality of transparent electrode pads respectively formed on the plurality of trigger pads, and a width of each trigger pad is greater than a width of the corresponding transparent electrode pad, and a thickness of each trigger pad is 3% -10% of a thickness of the corresponding transparent electrode pad.
Preferably, the non-contact sorting device as described above, wherein the thickness of each trigger pad and the thickness of the first doped layer are respectively 1% to 5% of the thickness of the I-type layer, and the thickness of each trigger pad is smaller than the thickness of the first doped layer.
Preferably, the non-contact sorting apparatus as described above, wherein the non-contact sorting apparatus further comprises:
the bonding layer is connected between the light triggering structure and the matching structure to jointly enclose and define an accommodating space, and the photodiode layer is correspondingly positioned in the accommodating space; a kind of electronic device with high-pressure air-conditioning system
The partition walls are positioned in the accommodating space and are connected with the light triggering structure and the matching structure; wherein, a plurality of partition walls are arranged in a row at intervals, a culture area is formed between any two adjacent partition walls, one side of the row of partition walls is provided with a first flow passage communicated with each culture area, and the other side of the row of partition walls is provided with a second flow passage communicated with each culture area;
the first runner can only pass through any one of the culture areas and be communicated with the second runner in the accommodating space of the non-contact sorting device.
The embodiment of the invention also discloses a light triggering structure of the non-contact sorting device, which comprises the following components:
a first substrate;
a first electrode layer formed on the first substrate;
a photodiode layer formed on the first electrode layer and having a thickness of 1-3 μm; wherein, photodiode layer includes: a first doped layer formed on the first electrode layer; the I-shaped layer is formed on the first doping layer, and a patterning groove is concavely formed on the I-shaped layer, so that the I-shaped layer forms a plurality of bosses which are arranged at intervals; wherein each boss has a width of 3-7 microns and a distance of no more than 2 microns between any two adjacent bosses;
An insulating layer is covered on the photodiode layer.
Preferably, the light triggering structure as described above, wherein the photodiode layer further includes a plurality of transparent electrode pads respectively formed on the plurality of bosses, and a width of each boss is greater than a width of the corresponding transparent electrode pad.
Compared with the prior art, the non-contact sorting device, the light triggering structure and the biological particle sorting equipment have the following beneficial effects:
the non-contact sorting device, the light triggering structure thereof and the biological particle sorting equipment disclosed by the embodiment of the invention adopt the photodiode layer with a specific structural design (such as a plurality of the triggering pads or a plurality of the bosses are separated by the distance and each have the width with a preset value), so that the non-contact sorting device can be beneficial to generating a relatively concentrated electric field (similar to the effect of point discharge) in a non-contact photoelectric coupling mode (through the triggering pads), and can be further used for accurately moving (or capturing) the target biological particles to any area.
Drawings
Fig. 1 is a schematic perspective view of a biological particle sorting apparatus according to a first embodiment of the present invention.
Fig. 2 is a schematic perspective sectional view of the biological particle sorting apparatus of fig. 1 for injecting a liquid sample.
Fig. 3 is a schematic cross-sectional view of fig. 1 along section line III-III.
Fig. 4 is an enlarged schematic view of the IV area in fig. 3.
Fig. 5 is a schematic cross-sectional view of fig. 1 along section line V-V.
Fig. 6 is a schematic perspective view of another embodiment of a biological particle sorting apparatus according to the present invention.
Fig. 7 is an enlarged partial schematic view of a biological particle sorting apparatus according to a second embodiment of the present invention.
Fig. 8 is an enlarged partial schematic view of a biological particle sorting apparatus according to a third embodiment of the present invention.
Fig. 9 is a schematic perspective view of a biological particle sorting apparatus according to a fourth embodiment of the present invention.
Fig. 10 is a schematic cross-sectional view of fig. 9 along section line X-X.
Fig. 11 is a schematic cross-sectional view of fig. 9 along section line XI-XI.
Fig. 12 is a schematic cross-sectional view of the biological particle sorting apparatus of fig. 11 for injecting a liquid sample and a culture fluid.
Fig. 13 is a schematic view of a subsequent operation of the biological particle sorting apparatus of fig. 12.
FIG. 14 is a schematic cross-sectional view of a biological particle sorting apparatus according to a fifth embodiment of the present invention.
Fig. 15 is a partially enlarged schematic illustration (one) of a biological particle sorting apparatus according to a sixth embodiment of the present invention.
FIG. 16 is a partially enlarged schematic illustration (II) of a biological particle sorting apparatus according to a sixth embodiment of the present invention.
Detailed Description
In order to make the technical problems, technical solutions and advantages to be solved by the present application more apparent, the following detailed description will be given with reference to the accompanying drawings and the specific embodiments. In the following description, specific details such as specific configurations and components are provided merely to facilitate a thorough understanding of embodiments of the present application. It will therefore be apparent to those skilled in the art that various changes and modifications can be made to the embodiments described herein without departing from the scope and spirit of the application. In addition, descriptions of well-known functions and constructions are omitted for clarity and conciseness.
It should be appreciated that reference throughout this specification to "one embodiment" or "an embodiment" means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the present application. Thus, the appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.
In various embodiments of the present application, it should be understood that the sequence numbers of the following processes do not mean the order of execution, and the order of execution of the processes should be determined by the functions and internal logic thereof, and should not constitute any limitation on the implementation process of the embodiments of the present application.
It should be understood that the term "and/or" is merely an association relationship describing the associated object, and means that three relationships may exist, for example, a and/or B may mean: a exists alone, A and B exist together, and B exists alone. In addition, the character "/" herein generally indicates that the front and rear associated objects are an "or" relationship.
In the examples provided herein, it should be understood that "B corresponding to a" means that B is associated with a from which B may be determined. It should also be understood that determining B from a does not mean determining B from a alone, but may also determine B from a and/or other information.
It will be understood that, although the terms "first," "second," "third," etc. may be used herein to describe various components or signals, these components or signals should not be limited by these terms. These terms are used primarily to distinguish one element from another element or signal from another signal.
Example 1
Please refer to fig. 1 to 6, which are a first embodiment of the present invention. As shown in fig. 1 and 2, the present embodiment discloses a biological particle sorting apparatus 1000 for sorting a target biological particle 301 from a liquid sample 300. That is, any sorting apparatus not used for biological particles is different from the biological particle sorting apparatus 1000 according to the present embodiment.
Wherein the liquid sample 300 may be a body fluid sample (e.g., blood, lymph, saliva, or urine) from an animal, and the target biological particles 301 may be a specific kind of cells, for example: circulating tumor cells (circulating tumor cells, abbreviated as CTC), fetal nucleated red blood cells (fetal nucleated red blood cells, abbreviated as FNRBC), viruses, or bacteria, but the invention is not limited thereto. For example, in other embodiments not shown in the present disclosure, the liquid sample 300 may also be a liquid sample from a plant.
Furthermore, the biological particle sorting apparatus 1000 in the present embodiment includes a non-contact sorting device 100 and an ac power device 200 electrically coupled to the non-contact sorting device 100, but the present invention is not limited thereto. For example, in other embodiments not shown, the non-contact sorting device 100 may be used alone (e.g., vending) or in combination with other devices. The specific construction of the non-contact type sorting apparatus 100 will be described first, and then the connection relationship with the ac power supply apparatus 200 will be described at a proper time.
It should be noted that, in the present embodiment, the non-contact sorting device 100 is of a chip-scale size (e.g. the thickness of the non-contact sorting device 100 is not greater than 100 μm), and the non-contact sorting device 100 is illustrated with a rectangular structure, but the invention is not limited thereto. For example, in other embodiments not shown in the present disclosure, the non-contact sorting device 100 may also have a curved configuration or an irregular configuration.
Further, the non-contact sorting device 100 in this embodiment includes a light triggering structure 1, a matching structure 2 spaced from the light triggering structure 1, and a bonding layer 3 connected between the light triggering structure 1 and the matching structure 2. For convenience of illustration, the matching structure 2 is transparent in this embodiment, but at least one of the matching structure 2 and the light triggering structure 1 may be transparent in practical application, so that the non-contact sorting apparatus 100 is normally operated.
As shown in fig. 2 to 4, the light triggering structure 1 includes a first substrate 11, a first electrode layer 12 formed on the first substrate 11, a photodiode layer 13 formed on the first electrode layer 12, and an insulating layer 14 covering the photodiode layer 13. The first electrode layer 12 may cover the entire surface of the first substrate 11, and the photodiode layer 13 is located between the first electrode layer 12 and the insulating layer 14 (i.e., the photodiode layer 13 is buried in the first electrode layer 12 and the insulating layer 14).
In this embodiment, the first substrate 11 is a glass plate, the first electrode layer 12 is a thin metal layer or an Indium Tin Oxide (ITO) layer, the photodiode layer 13 is a PIN-type diode layer with a thickness T13 of 1 micrometer (μm) to 3 micrometers (e.g., about 1.5 μm), and the insulating layer 14 is a silicon nitride layer or a silicon oxide layer with a thickness T14 of 10 nanometers (nm) to 100 nm.
In more detail, the photodiode layer 13 may include a first doped layer 131 formed on the first electrode layer 12, an I-type layer 132 formed on the first doped layer 131, a second doped layer 133 formed on the I-type layer 132, and a plurality of transparent electrode pads 134 formed on the second doped layer 133, but the present invention is not limited thereto. For example, in other embodiments not shown in the present disclosure, the photodiode layer 13 may be omitted or replaced by other structures instead of the transparent electrode pads 134 according to design requirements.
In this embodiment, the first doped layer 131 is an N-type layer (e.g., a highly doped N-type amorphous silicon layer) plated on the first electrode layer 12, and the first doped layer 131 preferably covers at least 90% of the area of the first electrode layer 12. The I-type layer 132 is a low doped (or undoped) I-type amorphous silicon layer plated on the first doped layer 131, and the I-type layer 132 preferably covers the entire first doped layer. That is, the first doped layer 131 and the I-type layer 132 are each configured monolithically in the present embodiment.
Furthermore, the second doped layer 133 is a P-type layer (e.g., a low doped P-type amorphous silicon layer) plated on the first doped layer 131, and the second doped layer 133 includes a plurality of trigger pads 1331 disposed at intervals, and a plurality of transparent electrode pads 134 are respectively formed on the plurality of trigger pads 1331. In the present embodiment, the plurality of trigger pads 1331 are arranged in a regular manner (e.g., in a matrix manner as shown in fig. 5), but the present invention is not limited thereto. For example, in other embodiments not shown in the present disclosure, the first doped layer 131 may be a P-type layer, and the second doped layer 133 may be an N-type layer.
Further, each trigger pad 1331 has a width W1331 ranging from 3 micrometers to 7 micrometers, and the width W1331 of each trigger pad 1331 (e.g., 5 micrometers) is preferably greater than the width W134 of the corresponding transparent electrode pad 134 (e.g., 3 micrometers), and a distance G (e.g., about 1 micrometer) of no greater than 2 micrometers is provided between any two adjacent trigger pads 1331.
In another aspect, the thickness T1331 of each trigger pad 1331 (e.g., about 10 nm) is 3% -10% of the thickness T134 of the corresponding transparent electrode pad 134 (e.g., about 200 nm). In addition, the thickness T1331 of each trigger pad 1331 and the thickness T131 of the first doped layer 131 are respectively 1% -5% of the thickness T132 of the I-type layer 132 (e.g., about 1000 nm), and the thickness T1331 of each trigger pad 1331 (e.g., about 10 nm) is smaller than the thickness T131 of the first doped layer 131 (e.g., about 20 nm).
It should be noted that, when the target biological particles 301 are viewed, any small variation in the non-contact sorting apparatus 100 will have a significant effect on the target biological particles 301, so in the above description, the size and arrangement of the components of the photodiode layer 13 that are advantageous for sorting the target biological particles 301 with a low external force are proposed, but the invention is not limited thereto.
The matching structure 2 includes a second substrate 21 and a second electrode layer 22 formed on the second substrate 21, and the second electrode layer 22 faces the light triggering structure 1. The bonding layer 3 is connected between the light triggering structure 1 and the matching structure 2 (e.g. the bonding layer 3 is connected between the insulating layer 14 and the second electrode layer 22) so as to jointly enclose and define a containing space C. The space between the insulating layer 14 and the second electrode layer 22 (e.g., the accommodating space C) of the non-contact sorting apparatus 100 can be used to accommodate the liquid sample 300 for a sorting operation corresponding to the target biological particles 301.
More specifically, at least one of the fitting structure 2 and the attaching layer 3 is formed with an input port E and an output port O (e.g. fig. 1 and 6) respectively connected to two ends of the accommodating space C; the non-contact sorting apparatus 100 can inject the liquid sample 300 from the input port E and flow the liquid sample 300 out of the output port O.
It should be noted that, in the present embodiment, the non-contact sorting device 100 is described by the light triggering structure 1 being matched with the matching structure 2 and the bonding layer 3, but the invention is not limited thereto. For example, in other embodiments of the invention not shown, the non-contact sorting device 100 may replace the attaching layer 3 by other structures; alternatively, the light triggering mechanism 1 may be used alone (e.g., vending) or in combination with other devices.
The ac power supply device 200 is electrically coupled to the first electrode layer 12 and the second electrode layer 22 of the non-contact sorting device 100. When the liquid sample 300 is located between the insulating layer 14 and the second electrode layer 22 of the non-contact sorting device 100, the non-contact sorting device 100 can be used to irradiate a light source P on at least one of the trigger pads 1331, so that a concentrated and non-uniform electric field is generated on the liquid sample 300, and a Dielectrophoresis (DEP) force capable of driving the target biological particles 301 to move is applied to the target biological particles.
As described above, the photodiode layer 13 of the biological particle sorting apparatus 1000 (or the non-contact sorting device 100) in the present embodiment has a specific structural design (e.g. the plurality of trigger pads 1331 are separated by the distance G and each have the width W1331 with a predetermined value, or the plurality of transparent electrode pads 134 are further added), so that it is beneficial to generate a relatively concentrated electric field (similar to the effect of tip discharge) through the trigger pads 1331 in a non-contact photoelectric coupling manner, and thus can be used to accurately move (or capture) the target biological particles 301 to any region.
Example two
Please refer to fig. 7, which is a diagram illustrating a second embodiment of the present invention. Since this embodiment is similar to the first embodiment, the same parts of the two embodiments will not be described again, and the difference between this embodiment and the first embodiment is mainly that: the photodiode layer 13.
In this embodiment, the I-type layer 132 is concavely provided with a patterned trench 1321, such that the I-type layer 132 forms a plurality of bosses 1322 arranged at intervals, and a plurality of trigger pads 1331 are respectively formed on the plurality of bosses 1322. The edge of each trigger pad 1331 is aligned with the edge of the corresponding boss 1322, and the depth D1321 of the patterned trench 1321 (e.g., about 20 nm) is 1% -5% of the thickness T132 of the I-layer 132.
Example III
Please refer to fig. 8, which is a diagram illustrating a third embodiment of the present invention. Since the present embodiment is similar to the first and second embodiments, the same parts of the above embodiments are not repeated, and the differences between the present embodiment and the first and second embodiments are mainly as follows: the photodiode layer 13.
In this embodiment, the I-type layer 132 includes a plurality of I-type pads 1323 disposed on the first doped layer 131 at intervals, and a plurality of trigger pads 1331 are respectively formed on the plurality of I-type pads 1323, and the width W1331 (e.g., about 5 microns) of each of the trigger pads 1331 is smaller than the width W1323 (e.g., about 10 microns) of the corresponding I-type pad 1323.
Furthermore, the first doped layer 131 preferably includes a plurality of spacers 1311 disposed on the first electrode layer 12 at intervals, and a plurality of I-shaped pads 1323 are respectively formed on the plurality of spacers 1311, and an edge of each I-shaped pad 1323 is aligned with an edge of the corresponding spacer 1311, but the present invention is not limited thereto. For example, in other embodiments not shown, the I-type layer 132 may include a plurality of I-type pads 1323, but the first doped layer 131 is configured as a single piece as in the first embodiment. In addition, the thickness of the insulating layer 14 can be adjusted according to design requirements.
Example IV
Please refer to fig. 9-13, which are a diagram illustrating a fourth embodiment of the present invention. Since the present embodiment is similar to the first to third embodiments, the same parts of the above embodiments are not repeated, and the differences between the present embodiment and the first to third embodiments are mainly as follows: the non-contact sorting device 100 in this embodiment further includes a plurality of partition walls 4 located in the accommodating space C and connecting the light triggering structure 1 and the matching structure 2.
In this embodiment, as shown in fig. 9 and 10, any of the partition walls 4 is made of a soft high bio-affinity material, for example: thick film photoresist (SU-8)/Polydimethylsiloxane (PDMS)/acrylic foam/silicone. Each of the partition walls 4 is connected between the insulating layer 14 and the second electrode layer 22 such that a part of the photodiode layer 22 (e.g., a part of the plurality of trigger pads 1331) is buried in a plurality of the partition walls 4.
Furthermore, as shown in fig. 10 to 13, a plurality of the partition walls 4 are arranged in a row at intervals, and a culture region R is formed between any two adjacent partition walls 4, one side of the row of partition walls 4 is formed with a first flow channel C1 communicating with each of the culture regions R, and the other side of the row of partition walls 4 is formed with a second flow channel C2 communicating with each of the culture regions R.
Further, when the first flow channel C1 is injected into the liquid sample 300, the non-contact sorting device 100 can be used to irradiate a light source onto the photodiode layer 13 (e.g. the light irradiation area surrounded by the dot chain line in FIG. 12 and FIG. 13) so as to apply a dielectrophoresis force to the target biological particles 301, and further can drive the target biological particles 301 to move to one of the culture areas R and be restrained by the light source so as not to move to the second flow channel C2.
Accordingly, the non-contact type sorting apparatus 100 (or the biological particle sorting apparatus 1000) is configured with a double-flow-path structure (e.g., the first flow path C1 and the second flow path C2) communicating with each of the culture regions R through the plurality of partition walls 4 in the present embodiment, so that the target biological particles 301 entering any one of the culture regions R from the first flow path C1 can flow to the second flow path C2, thereby effectively improving the culture or growth effect of the target biological particles 301.
Furthermore, the plurality of trigger pads 1331 disposed in each of the culture regions R of the non-contact sorting apparatus 100 can be designed to facilitate the stimulation of the target biological particles 301 located in the culture regions R by designing a specific structure (e.g., the plurality of trigger pads 1331 are spaced apart by the distance G and each have the width W1331 of a predetermined value).
It should be noted that at least one of the matching structure 2 and the lamination layer 3 is formed with a first input port E1 and a first output port O1 respectively connected to the ends of the first flow channel C1, and at least one of the matching structure 2 and the lamination layer 3 is formed with a second input port E2 and a second output port O2 respectively connected to the two ends of the second flow channel C2.
In the present embodiment, the first flow channel C1 has a first flow direction F1 (e.g. the direction in which the first input port E1 faces the first output port O1), the second flow channel C2 defines a second flow direction F2, which is preferably parallel to the first flow direction F1, and the width of the second flow channel C2 is preferably smaller than the width of the first flow channel C1, but the present invention is not limited thereto. Furthermore, the first input port E1 is adjacent to the second input port E2, and the first output port O1 is adjacent to the second output port O2.
Accordingly, the non-contact sorting apparatus 100 can inject the liquid sample 300 from the first input port E1 and flow the liquid sample 300 out from the first output port O1; the non-contact sorting apparatus 100 can inject a culture solution 400 into the second input E2 and make the culture solution 400 flow out from the second output O2.
In more detail, each of the culture regions R has a first opening R1 communicating with the first flow channel C1 and a second opening R2 communicating with the second flow channel C2, and the first opening R1 is larger than the second opening R2 (e.g., about 2 μm); in the accommodation space C of the non-contact sorting apparatus 100, the first flow channel C1 may communicate with the second flow channel C2 through any one of the culture regions R.
The plurality of partition walls 4 have numerous embodiments satisfying the above conditions, and for convenience of description, the present embodiment describes the structure of the partition walls 4 in only one preferred embodiment, but the invention is not limited thereto. Furthermore, the structural design of the plurality of partition walls 4 in the present embodiment is substantially the same, and the structure of two partition walls 4 at the end is slightly different from that of the other partition walls 4. For convenience of description, the structural design of the partition wall 4 is described below, but the invention is not limited thereto.
Specifically, the partition wall 4 includes an elongated partition section 41, two first guide sections 42 connected to one end of the partition section 41, and two second guide sections 43 connected to the other end of the partition section 41. Wherein the partition section 41 is perpendicular to the first flow direction F1 (or the second flow direction F2), any one of the first guiding sections 42 and the partition section 41 forms a first included angle α1 between 110 degrees and 160 degrees, any one of the second guiding sections 43 and the partition section 41 forms a second included angle α2 between 100 degrees and 160 degrees, and the length of any one of the second guiding sections 43 is preferably greater than the length of any one of the first guiding sections 42, but the invention is not limited thereto.
In another aspect, among any two adjacent partition walls 4, two first guide sections 42 adjacent to each other but different from each other of the partition walls 4 define a first opening R1 together, and two second guide sections 43 adjacent to each other but different from each other of the partition walls 4 define a second opening R2 together, and the first opening R1 is larger than the second opening R2 (e.g., about 2 μm), so as to facilitate the target biological particles 301 from the first flow C1 through the first opening R1 into the culture region R and to restrict the target biological particles 301 from moving to the second flow channel C2 due to the second opening R2.
Furthermore, of the two first guide sections 42 of any one of the defined first openings R1, a length of one of the first guide sections 42 located upstream of the first flow direction F1 is longer than a length of the other first guide section 42, so that the liquid sample 300 contacts the first flow direction F1 at an acute angle α between 70 degrees and 20 degrees. Accordingly, the first guide section 42 having a larger length can prevent the cells in the liquid sample 300 from accidentally falling into the corresponding culture region R.
It should be noted that, in the non-contact sorting apparatus 100, other structures matched with the plurality of partition walls 4 can be adjusted and changed according to design requirements, and the invention is not limited to the first to third embodiments. For example, in other embodiments not shown in the present disclosure, the photodiode layer 13 may be configured other than a PIN diode layer.
Example five
Please refer to fig. 14, which is a diagram illustrating a fifth embodiment of the present invention. Since this embodiment is similar to the fourth embodiment, the same parts of the two embodiments will not be described again, and the difference between this embodiment and the fourth embodiment is mainly that: a plurality of said partition walls 4.
In this embodiment, at least one of the two adjacent partition walls 4 is formed with a layout section 44 located in the corresponding culture region R to lengthen the path of the liquid sample 300 flowing from the first opening R1 to the second opening R2, so as to effectively avoid the objects of the liquid sample 300 that are not the target biological particles 301 from flowing into the culture region R.
Example six
Please refer to fig. 15 and 16, which are schematic diagrams illustrating a sixth embodiment of the present invention. Since the present embodiment is similar to the second embodiment, the same parts of the two embodiments will not be described again, and the difference between the present embodiment and the second embodiment is that: the photodiode layer 13.
In this embodiment, as shown in fig. 15, the photodiode layer 13 only includes the first doped layer 131 formed on the first electrode layer 12 and an I-type layer 132 formed on the first doped layer 131. The I-type layer 132 is concavely provided with the patterned trenches 1321, so that the I-type layer 132 forms a plurality of the bosses 1322 arranged at intervals. Further, each of the bosses 1322 has a width W1322 (e.g., 5 microns) of 3-7 microns, and a distance G (e.g., 1 micron) of not more than 2 microns between any two adjacent bosses 1322.
Furthermore, as shown in fig. 16, the photodiode layer 13 may further include a plurality of transparent electrode pads 134 respectively formed on the plurality of bosses 1322, and the width W1322 of each boss 1322 is greater than the width W134 (e.g., 3 μm) of the corresponding transparent electrode pad 134.
In summary, the non-contact sorting device, the optical triggering structure thereof and the biological particle sorting apparatus according to the embodiments of the present invention employ the photodiode layer with a specific structural design (e.g. the triggering pads or the bosses are separated by the distance and each have the width of a predetermined value, or the transparent electrode pads are further added), so that the non-contact photoelectric coupling manner is facilitated to generate a relatively concentrated electric field (similar to the effect of tip discharge) through the triggering pad, and thus the photodiode layer can be used to accurately move (or capture) the target biological particles to any region.
In addition, the non-contact type sorting device and the biological particle sorting apparatus according to the embodiments of the present invention are configured by a plurality of partition walls, and a double-flow-path structure (e.g., the first flow path and the second flow path) is formed in communication with each of the culture areas, so that the target biological particles entering any one of the culture areas from the first flow path can flow to the second flow path, thereby effectively improving the culture effect of the target biological particles.
Further, the non-contact sorting device is configured to facilitate the stimulation of the target biological particles located in the culture zone by designing a specific structure (e.g., the plurality of trigger pads are spaced apart by the distance and each have the width of a predetermined value) in the plurality of trigger pads disposed in each of the culture zones.
Furthermore, the present application may repeat reference numerals and/or letters in the various examples. This repetition is for the purpose of simplicity and clarity and does not in itself dictate a relationship between the various embodiments and/or configurations discussed.
While the foregoing is directed to the preferred embodiments of the present application, it should be noted that modifications and adaptations to those embodiments may occur to one skilled in the art and that such modifications and adaptations are intended to be comprehended within the scope of the present application without departing from the principles set forth herein.
Claims (20)
1. A biological particle sorting apparatus for sorting a target biological particle from a liquid sample, the apparatus comprising: a non-contact sorting device and an alternating current power supply device;
the non-contact sorting device comprises:
A light triggering structure, the light triggering structure comprising: a first substrate; a first electrode layer formed on the first substrate; a photodiode layer formed on the first electrode layer and having a thickness of 1-3 microns; wherein, the photodiode layer includes: a first doped layer formed on the first electrode layer; an I-type layer formed on the first doped layer; and a second doped layer comprising a plurality of trigger pads formed on the I-type layer and spaced apart from each other; wherein each trigger pad has a width of 3-7 microns, and a distance of not more than 2 microns is provided between any two adjacent trigger pads; an insulating layer covering the photodiode layer;
the matching structure is arranged at intervals with the light triggering structures, at least one of the matching structure is transparent, the matching structure comprises a second substrate and a second electrode layer formed on the second substrate, and the second electrode layer faces the light triggering structures;
the alternating current power supply device is electrically coupled with the first electrode layer and the second electrode layer;
When the liquid sample is located between the insulating layer and the second electrode layer of the non-contact sorting device, the non-contact sorting device is used for being irradiated by a light source on at least one trigger pad, so that the non-contact sorting device generates a concentrated and non-uniform electric field at the liquid sample, and a dielectrophoresis force capable of driving the target biological particles to move is applied to the target biological particles.
2. The biological particle sorting apparatus of claim 1, wherein the photodiode layer further comprises a plurality of transparent electrode pads respectively formed on a plurality of the trigger pads, and the width of each of the trigger pads is greater than the width of the corresponding transparent electrode pad.
3. The biological particle sorting apparatus of claim 2, wherein the thickness of each trigger pad is 3% to 10% of the thickness of the corresponding transparent electrode pad.
4. The biological particle sorting apparatus of claim 1, wherein the first doped layer covers at least 90% of the area of the first electrode layer and the type I layer covers the entire first doped layer.
5. The biological particle sorting apparatus of claim 4, wherein the I-type layer is concavely provided with a patterned groove such that the I-type layer forms a plurality of bosses arranged at intervals, and a plurality of trigger pads are respectively formed on the plurality of bosses.
6. The biological particle sorting apparatus of claim 5, wherein an edge of each trigger pad is aligned with an edge of the corresponding boss and the depth of the patterned trench is 1% -5% of the thickness of the I-layer.
7. The biological particle sorting apparatus of claim 1, wherein the I-shaped layer comprises a plurality of I-shaped pads disposed on the first doped layer at intervals, and a plurality of trigger pads are respectively formed on the plurality of I-shaped pads, and the width of each of the trigger pads is smaller than the width of the corresponding I-shaped pad.
8. The biological particle sorting apparatus of claim 7, wherein the first doped layer includes a plurality of spacers disposed on the first electrode layer at intervals, and a plurality of the I-pads are respectively formed on the plurality of spacers, and an edge of each of the I-pads is aligned with an edge of the corresponding spacer.
9. The biological particle sorting apparatus of claim 1, wherein the thickness of each of the trigger pads and the thickness of the first doped layer are each 1% -5% of the thickness of the I-layer, and the thickness of each of the trigger pads is less than the thickness of the first doped layer.
10. The biological particulate sorting apparatus of claim 1, wherein the non-contact sorting device further comprises:
the bonding layer is connected between the light triggering structure and the matching structure to jointly enclose and define an accommodating space, and the photodiode layer is correspondingly positioned in the accommodating space; a kind of electronic device with high-pressure air-conditioning system
The partition walls are positioned in the accommodating space and are connected with the light triggering structure and the matching structure; wherein a plurality of partition walls are arranged in a row at intervals, a culture area is formed between any two adjacent partition walls, one side of each partition wall of the row is provided with a first flow passage communicated with each culture area, and the other side of each partition wall of the row is provided with a second flow passage communicated with each culture area;
when the first flow channel is injected into the liquid sample, the non-contact sorting device can drive the target biological particles to move to one culture area by moving the light source and can not move to the second flow channel due to the restraint of the target biological particles.
11. The biological particle sorting apparatus of claim 10, wherein portions of a plurality of said trigger pads are embedded within a plurality of said compartment walls, each of said compartment walls comprising:
a separator segment;
two first guide sections connected to one end of the partition board section, and each first guide section and the partition board section form a first included angle between 110 degrees and 160 degrees; a kind of electronic device with high-pressure air-conditioning system
Two second guide sections connected to the other end of the partition board section, wherein any one of the second guide sections forms a second included angle of 100-160 degrees with the partition board section;
wherein, in any two adjacent partition walls, two first guide sections adjacent to each other and respectively belonging to different partition walls jointly define a first opening, two second guide sections adjacent to each other and respectively belonging to different partition walls jointly define a second opening, and the first opening is larger than the second opening.
12. The biological particle sorting apparatus of claim 11, wherein the first flow channel has a first flow direction; among the two first guide sections defining any one of the first openings, one of the first guide sections located upstream in the first flow direction has a length greater than that of the other first guide section, and is configured to contact the liquid specimen in the first flow direction at an acute angle between 70 degrees and 20 degrees.
13. The biological particle sorting apparatus of claim 10, wherein each of the culture zones has a first opening in communication with the first flow channel and a second opening in communication with the second flow channel, and wherein the first opening is larger than the second opening; in the accommodating space of the non-contact sorting device, the first flow channel may be communicated with the second flow channel through any one of the culture areas.
14. The biological particle sorting apparatus of claim 13, wherein at least one of any two adjacent partition walls is formed with a layout section in the corresponding culture area for extending the path of the liquid sample flowing from the first opening to the second opening.
15. A non-contact sorting apparatus for sorting a target biological particle from a liquid sample, the non-contact sorting apparatus comprising: a light triggering structure and a matching structure;
the light triggering structure comprises:
a first substrate;
a first electrode layer formed on the first substrate;
a photodiode layer formed on the first electrode layer and having a thickness of 1-3 microns; wherein, the photodiode layer includes: a first doped layer formed on the first electrode layer; an I-type layer formed on the first doped layer; a second doped layer comprising a plurality of trigger pads formed on the I-type layer and spaced apart from each other; wherein each trigger pad has a width of 3-7 microns, and a distance of not more than 2 microns is provided between any two adjacent trigger pads; and an insulating layer covering the photodiode layer;
The matching structure and the light triggering structure are arranged at intervals, at least one of the matching structure and the light triggering structure is transparent, the matching structure comprises a second substrate and a second electrode layer formed on the second substrate, and the second electrode layer faces the light triggering structure;
the non-contact sorting device comprises an insulating layer, a second electrode layer, a liquid sample and a liquid sample, wherein the insulating layer and the second electrode layer of the non-contact sorting device can be used for accommodating the liquid sample so as to perform a sorting operation corresponding to the target biological particles.
16. The non-contact sorting apparatus of claim 15, wherein the photodiode layer further comprises a plurality of transparent electrode pads respectively formed on a plurality of the trigger pads, and the width of each of the trigger pads is greater than the width of the corresponding transparent electrode pad, and the thickness of each of the trigger pads is 3% -10% of the thickness of the corresponding transparent electrode pad.
17. The non-contact sorting device of claim 16, wherein the thickness of each trigger pad and the thickness of the first doped layer are each 1% -5% of the thickness of the type I layer, and the thickness of each trigger pad is less than the thickness of the first doped layer.
18. The non-contact sorting device of claim 15, further comprising:
the bonding layer is connected between the light triggering structure and the matching structure to jointly enclose and define an accommodating space, and the photodiode layer is correspondingly positioned in the accommodating space; a kind of electronic device with high-pressure air-conditioning system
The partition walls are positioned in the accommodating space and are connected with the light triggering structure and the matching structure; wherein a plurality of partition walls are arranged in a row at intervals, a culture area is formed between any two adjacent partition walls, one side of each partition wall of the row is provided with a first flow passage communicated with each culture area, and the other side of each partition wall of the row is provided with a second flow passage communicated with each culture area;
wherein, in the accommodating space of the non-contact sorting device, the first flow channel can only communicate with the second flow channel through any one of the culture areas.
19. A light triggering mechanism of a non-contact sorting apparatus, characterized in that the light triggering mechanism of the non-contact sorting apparatus comprises:
A first substrate;
a first electrode layer formed on the first substrate;
a photodiode layer formed on the first electrode layer and having a thickness of 1-3 microns; wherein, the photodiode layer includes: a first doped layer formed on the first electrode layer; the I-shaped layer is formed on the first doping layer, and a patterning groove is concavely formed in the I-shaped layer, so that a plurality of bosses which are arranged at intervals are formed in the I-shaped layer; wherein each boss has a width of 3-7 microns and a distance of no more than 2 microns is provided between any two adjacent bosses;
and an insulating layer covering the photodiode layer.
20. The light triggering mechanism of claim 19, wherein the photodiode layer further comprises a plurality of transparent electrode pads formed on a plurality of the bosses, respectively, and the width of each boss is greater than the width of the corresponding transparent electrode pad.
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