WO2023125489A2

WO2023125489A2 - Optical tweezer apparatus based on phototransistors having equal-density arrangement in oblique direction, and microfluidic device

Info

Publication number: WO2023125489A2
Application number: PCT/CN2022/142199
Authority: WO
Inventors: 李培炼; 缪小虎; 程鹏
Original assignee: 彩科(苏州)生物科技有限公司
Priority date: 2021-12-28
Filing date: 2022-12-27
Publication date: 2023-07-06
Also published as: CN116393068A; WO2023125489A3

Abstract

The invention provides: a first electrode; a second electrode; a phototransistor array arranged between the first electrode and the second electrode, the phototransistor array comprising a plurality of bipolar phototransistors, and each of the phototransistors being physically isolated from one another via an insulating element; the plurality of phototransistors are regularly arranged, and are arranged at a first interval in a transverse direction and at a second interval in a longitudinal direction; transistors which are adjacent in the longitudinal direction are staggered in the transverse direction, and a line connecting center points of the adjacent transistors is oblique; transistors along the oblique direction are arranged at a third interval, and the third interval is substantially equal to the first interval or to the second interval. Transistor optical tweezers provided in the present invention have a transistor array arrangement density in a transverse direction or longitudinal direction which is substantially equal to the arrangement density thereof in an oblique direction, allowing for generating a balanced DEP force, and for more convenient and precise operations regarding cells and other micro-scale objects.

Description

Optical tweezers and microfluidic devices based on oblique equi-density arrangement of phototransistors

technical field

The invention relates to an optical tweezer device based on a phototransistor, in particular to phototransistors arranged in an oblique direction with equal density, an optical tweezer device comprising the phototransistor, and a microfluidic device comprising the optical tweezer device.

Background technique

Transistor-based optical tweezers have been applied to manipulate (e.g. select or move) micro-objects such as cells, microspheres, etc. This type of optical tweezers device includes a phototransistor array, which typically includes phototransistors distributed in an array and physically isolated from each other. A typical phototransistor array is a regular rectangular (usually square) array etched on a silicon substrate by semiconductor technology. These rectangular phototransistors are regularly arranged and precisely aligned. For example, see CN 107223074 B and CN 105849561 B.

With reference to Fig. 1 A, it has shown the optical tweezers device 136 of prior art, and it comprises the first electrode 124 that is made of the glass 128 that is coated with indium tin oxide (ITO) conductive coating 114 and the second electrode 124 that is electrically connected with the first electrode 124. Electrode 116, an alternating current AC is applied between the two electrodes. An array transistor structure is disposed on the second electrode 116 and is electrically connected to the second electrode 116 . A microfluidic channel 122 is provided between the upper surface of the transistor array and the lower surface of the conductive plating layer 114 of the first electrode 124 . The microfluidic channel 122 is generally composed of a plurality of microfluidic channels connected in series or in parallel, and each microfluidic channel contains a plurality of addressable microwells, and cells or other microobjects can be located in the microwells. Microfluidic channels 122 include fluidic ports (not shown) for fluid communication with the outside world, microfluidic fluids (such as cell culture fluid) containing cells 118 (illustrated as

cells

118a, 118b, and 118c, such as hybridoma cells that secrete antibodies). or physiological fluid) flows into the microchannel 122 through the inlet, flows through the microchannel 122 in the direction indicated by arrow A to undergo processing and operations (including photoelectric detection, cultivation, screening, movement, etc.), and finally flows out from the outlet to realize microfluidic control. The operating procedure of the chip. When the patterned light beam 152 is irradiated on a specific region of the transistor array, the corresponding transistor is turned on, thereby generating an electric field 154 at the corresponding position in the microfluidic channel 122, and the electric field generates a dielectrophoretic force on the surrounding cells 118a, thereby pushing or The cells 118 are attracted to move.

The phototransistor array includes a plurality of transistors 126 arranged in an array, and each transistor 126 is physically separated by an insulating cover layer 112, 113 (FIG. 1B) and an insulating barrier 148 (for example, all made of _SiO2 material). , so as to achieve electrical insulation. Each transistor 126 is equidistantly distributed in the form of a cube or a cuboid. The transistor 126 includes a substrate layer 110 , a collector region 108 disposed on the substrate layer, a base region 106 disposed on the collector region 108 , and emitter regions 102 and 104 disposed on the base region 106 .

Referring to FIG. 1B , it shows a partial top view of the optical tweezers device 136 shown in FIG. 1A (the first electrode 124 is omitted for clarity). The phototransistors are regularly arranged in a rectangular shape and are precisely aligned both laterally and vertically. When the cell 118 of interest is to move from the point S to the expected end point E2 along the arrow B, usually a plurality of transistors can be excited around the cell 118, which can be realized by controlling a correspondingly shaped light beam to irradiate on the transistor. However, as shown in the figure, in the transistor array arranged in this way, the intervals C1a-C1c between laterally adjacent transistors are significantly smaller than the intervals C1a-C1b between obliquely adjacent transistors, that is, lateral transistors (similarly, The arrangement density of vertical transistors) is greater than that of oblique transistors. And, when the number of transistors spanned by the excitation light beam is larger, the impact caused by the difference in arrangement density is greater. The direct consequence of this is that when the lateral length of the patterned excitation beam is the same as the oblique length, the average number of lateral transistors excited by it is greater than the average number of oblique transistors, so the lateral photogenerated current intensity is greater than the oblique photogenerated current intensity, That is, the transverse DEP force is greater than the oblique DEP force, causing the actual movement end point E1 of the cell 118 to deviate from the expected end point E2 in the longitudinal direction. In theory, part of the deviation can be offset by adjusting the lateral and oblique lengths of the patterned beam, but lateral or oblique transistors are not available in every case (e.g., covered by cells); The interval of the beam always changes, resulting in a corresponding change in the adjustment range of the transverse length and oblique length of the beam, which undoubtedly significantly increases the difficulty of practical operation, making it commercially unfeasible.

In view of this, there is a need in the art for an improved optical tweezers device and corresponding microfluidic devices to overcome the above-mentioned defects in the prior art.

Contents of the invention

One aspect of the present invention provides a transistor optical tweezers, comprising: a first electrode; a second electrode capable of being electrically connected to the first electrode; a phototransistor array arranged between the first electrode and the second electrode, the phototransistor The array includes a plurality of bipolar phototransistors, each phototransistor is physically separated by an insulating element; and a microfluidic channel disposed between the first electrode and the phototransistor array, the microfluidic channel includes a plurality of micropores , wherein the plurality of phototransistors are regularly arranged and arranged with a first pitch in the lateral direction, and arranged with a second pitch in the vertical direction, wherein adjacent transistors located in adjacent vertical directions are staggered from each other in the lateral direction and the phase The direction of the connection line between the central points of the adjacent transistors constitutes an oblique direction, and the transistors on the oblique direction are arranged with a third pitch, wherein the third pitch is substantially equal to the first pitch or the second pitch.

In some embodiments, the first pitch is different in size from the second pitch. In some embodiments, the first pitch is smaller than the second pitch. In some embodiments, the first pitch is greater than the second pitch.

In some embodiments, the plurality of phototransistors are regularly arranged in repeating units of regular or irregular shape. In a preferred embodiment, the plurality of phototransistors are regularly arranged in circles or hexagons as repeating units.

In some embodiments, the plurality of phototransistors are regularly arranged in a hexagon as a repeating unit, and the hexagon is formed by a cross-section of a hexagonal prism phototransistor.

In some embodiments, the plurality of phototransistors are regularly arranged in a hexagon as a repeating unit, and the hexagon is composed of six triangles, and the six triangles are composed of six three-dimensional structures physically isolated from each other. Cross-sectional composition of a prismatic phototransistor. In some embodiments, the triangles are arranged such that one side of the hexagon is disposed transversely.

In some embodiments, the plurality of phototransistors are regularly arranged in a circle as a repeating unit, and each circle is formed by a cross section of a cylindrical phototransistor.

In some embodiments, the plurality of phototransistors are integrated on a common semiconductor substrate, and each phototransistor includes a base region, an emitter region and a collector region.

In some embodiments, the microfluidic channel comprises a conductive medium having cells at least two of the plurality of phototransistors are activated to manipulate the cells.

In some embodiments, in the transistor optical tweezers of the present invention, the lateral and oblique light patterns per unit length generate photocurrents with substantially the same intensity in the lateral and oblique directions, respectively. In some embodiments, the longitudinal and oblique light patterns per unit length generate substantially the same intensity of photogenerated current in the longitudinal and oblique directions, respectively.

In some embodiments, no metal electrodes are arranged on the surface of the phototransistor array.

Another aspect of the present invention provides a microfluidic device, which includes any transistor optical tweezers described in the present invention, a control system, an image acquisition system, and an optical pattern generation device.

In some embodiments, the light pattern generated by the light pattern generating device covers at least two adjacent phototransistors.

In some embodiments, the light pattern generated by the light pattern generating device includes oblique lengths. In some embodiments, the light pattern generated by the light pattern generating device further includes a horizontal length or a vertical length. In some embodiments, the oblique length is substantially equal to the transverse or longitudinal length.

In some embodiments, the microfluidic device does not include an electrowetting device.

In the transistor optical tweezers provided by the present invention, the transistor array has substantially the same arrangement density in the lateral or vertical part and the oblique part, for example, the number of transistors covered by a unit length in the lateral and oblique directions is substantially equal, or in the lateral and oblique directions. The area of the transistors covered by the upward unit length is basically the same, or the number of transistors covered by the unit length in the vertical direction and the oblique direction is basically the same, or the area of the transistors covered by the unit length in the vertical direction and the oblique direction is basically the same. When using horizontal/vertical and oblique light beams of the same length to excite transistors, the number or area of transistors covered in each direction is equal, thus generating equal photocurrents in each direction, resulting in a balanced DEP force, making cells and other micro-objects operation as expected. When using lateral/vertical portions and oblique portions with different lengths, since the number or area of transistors covered per unit length is equal, the number of transistors or areas covered by each of the lateral/vertical portions and oblique portions can be It is known in advance, so the DEP force generated by it can also be determined in advance, and the path that micro-objects such as cells can be moved can also be predicted, making the manipulation of micro-objects more convenient and accurate.

Description of drawings

The invention will be described in more detail with reference to the accompanying drawings. It should be noted that the illustrated solution is only a representative example of the embodiment of the present invention, and in order to explain the details of the exemplary embodiment more clearly, the elements in the drawings are not drawn to the same scale as the actual size, and the number of the actual elements It can be changed, and the relative positional relationship of actual components is basically consistent with the illustrations, and some components are not shown. In the case of multiple embodiments, when one or more features described in the previous embodiment can also be applied to another embodiment, for the sake of brevity, the following one or more embodiments will not be repeated. These reapplicable features, the following one or more embodiments should be understood to have described these reapplicable features, unless otherwise stated. Those skilled in the art will appreciate after reading this disclosure that one or more features shown in one figure can be combined with one or more features shown in another figure to create one or more features not shown in the figures. Alternative embodiments are specifically shown in , and these alternative embodiments also form a part of the present invention.

FIG. 1 schematically shows an optical tweezers device in the prior art, wherein FIG. 1A is a partial cross-sectional view, and FIG. 1B is a partial top view.

Fig. 2 schematically shows a partial top view of an optical tweezers device according to an embodiment of the present invention.

Fig. 3 schematically shows a partial top view of an optical tweezers device according to another embodiment of the present invention.

Fig. 4 schematically shows a partial top view of an optical tweezers device according to yet another embodiment of the present invention.

Fig. 5 schematically shows a partial top view of an optical tweezers device according to yet another embodiment of the present invention.

6 is a schematic structural view of a phototransistor used in an optical tweezer device according to an embodiment of the present invention, wherein FIG. 6A is a schematic structural view of a phototransistor used in the optical tweezer device shown in FIG. 2 or FIG. 3 , and FIG. 6B and FIG. 6C is a schematic structural view of different sides of the phototransistor used in the optical tweezers device shown in FIG. 5 .

FIG. 7 schematically shows a flow chart of manufacturing a transistor array of an optical tweezers device according to an embodiment of the present invention.

The meanings represented by the reference signs are summarized as follows. Reference numerals with the same number designate the same element, and when applicable, repetitions of the same element are indicated by a letter after the number. For example,

reference numerals

118a, 118b, and 118c represent three repetitions of element 118 . 102, 202, 502-first doped region; 104, 204, 504-second doped region; 105, 205, 505-emitter region; 106, 206, 506-base region; 108, 208, 508-collector 110, 210, 510-substrate; 112, 212, 312-insulating cover; 114-conductive plating; 116-second electrode; 118-cell; 120-first insulating element; 122-microfluidic channel; 124 - first electrode; 126, 226, 326, 426, 526 - phototransistor; 128 - first electrode plate; 136, 236, 336, 436, 536 - optical tweezers device; 140 - second insulating element; 152 - patterning Beam; 154-non-uniform electric field; 256-horizontal; 258-longitudinal; D-spacing; P, Q, T, V-start and end of the patterned beam.

Detailed ways

Exemplary embodiments of the present invention will be described in detail below with reference to the accompanying drawings. It should be understood that the scope of the present invention is not limited to the disclosed embodiments, and those skilled in the art can modify and change these exemplary embodiments based on the teachings of the present invention after reading the disclosed content of the present invention without requiring Such modifications and variations are intended to be embraced within the scope outlined by the appended claims as an exercise of inventive effort.

FIG. 2 schematically shows a partial top view of an optical tweezers device 236 according to an embodiment of the present invention. The transistor array of the optical tweezers device 236 includes regularly arranged bipolar phototransistors 226 , and the phototransistors 226 are physically isolated by an insulating material 212 (such as SiO ₂ ). Transistor 226 can be seen in its emitter region 202 in the figure. The emission area 202 is exposed to the microfluidic channel, and is in direct contact with the conductive medium (such as cell culture fluid, physiological fluid, detection medium) and the contained microobjects (such as cells or fluorescent microspheres) in the microfluidic channel. Typically, micro-objects are sized to cover at least two adjacent phototransistors 226 and are expected to be moved across at least one phototransistor 226 .

In this embodiment, the cross-sectional shape of the phototransistor 226 is a regular hexagon. The transistors 226 are arranged with a first pitch D1 in the lateral direction 256 and arranged with a second pitch D2 in the vertical direction 258 . The first distance D1 represents the distance between the center points of the adjacent transistors 226 in the same horizontal direction, and the second distance D2 represents the distance between the center points of the adjacent transistors 226 in the same vertical direction. In this embodiment, the first distance D1 is smaller than the second distance D2. Adjacent transistors 226a and 226c (or 226b and 226d, or 226b and 226c, or 226e and 226d) located in adjacent

vertical directions

258a and 258b are staggered from each other in the lateral direction 256, that is, the center points of adjacent transistors 226a and 226c The direction of the connecting line is not parallel to or intersects with the horizontal direction 256 . In this embodiment,

transistors

226a, 226b, 226c, 226d and 226e have center points C2a, C2b, C2c, C2d and C2e respectively, all of which are represented by solid circles in the figure, and the distance from the center point to each side of the hexagon equal.

In this embodiment, the connecting lines C2a-C2c, C2b-C2c, C2b-C2d or C2d-C2e of the center points of adjacent transistors 226a and 226c (or 226b and 226d, or 226b and 226c, or 226e and 226d) are The direction of is defined as oblique, where C2a-C2c is parallel to the direction of C2b-C2d, and C2b-C2c is parallel to the direction of C2d-C2e. The diagonally upward transistors are arranged with a third pitch D3. In this embodiment, the third distance D3 is equal to the second distance D2.

When the cell 218a is to be driven toward the microwell (generally in the longitudinal direction 258 as shown), the patterned light beams P1-P2-P3 are projected onto corresponding regions of the transistor array, thereby exciting the corresponding transistors and generating The DEP force, which controls the movement of the light beams P1-P2-P3, can manipulate the cell 218a. For example, the light beams P1 - P2 - P3 can be projected to the center of the transistor 226 or cover the entire transistor 226 . The light beams P1-P2-P3 may have equal oblique portions P1-P3 and longitudinal portions P1-P2. In this embodiment, since the vertical distance D2 is equal to the oblique distance D3, the number (or area) of the transistors covered by the oblique portion P1-P3 of the light beam is the same as the number (or area) of the transistors covered by the vertical portion P1-P2 ( or areas) are equal, for example, they both cover two adjacent transistors 226 . Therefore, the longitudinal DEP force and oblique DEP force generated by the light beam are equal, so that it is easier to drive the cell 218a with a more balanced force to move to the cell 218a shown in dotted line as expected, avoiding the expected end point and the actual end point deviation.

In this embodiment, by rationally selecting the arrangement and shape of the transistors, the transistor array has substantially the same arrangement density in the oblique part and the vertical part (for example, the number of transistors covered by a unit length is basically equal, or the number of transistors covered by a unit length is basically equal). The area of the covered transistors is substantially equal). It is worth noting that this embodiment does not rely on the beams P1-P2-P3 having equal oblique portions P1-P3 and longitudinal portions P1-P2. For example, the length of the oblique portion may be greater than the length of the longitudinal portion, or the length of the oblique portion may be smaller than the length of the longitudinal portion. When using vertical sections and oblique sections with different lengths, since the number or area of transistors covered by a unit length is equal, the number or area of transistors covered by the vertical section and the oblique section can be calculated in advance , and thus the DEP force it generates can also be predetermined, and the path along which cells can be moved can thus be predicted.

For example, the illustrated beams P3-P4-P5 may be used to control the movement of the cell 218b. The light beam P3-P4-P5 has an oblique portion P3-P4 and a longitudinal portion P3-P5, wherein the length of the oblique portion P3-P4 is greater than the length of the longitudinal portion P3-P5. As shown in the figure, the oblique portion P3-P4 covers three adjacent transistors on three adjacent vertical lines 258, and the vertical portion P3-P5 covers two adjacent transistors on the same vertical line 258, so the oblique portion P3-P4 has a greater DEP force than the longitudinal sections P3-P5, driving the cell 218b towards the cell 218b indicated by the dashed line compared to a position driven by a beam having equal longitudinal and oblique sections The position of the end point is biased to the left of the illustration.

In addition, the light beam controlling the movement of the cell 218 does not necessarily have a longitudinal portion, for example, the light beam may only have an oblique portion, as shown by light beams P6-P7-P8 in the figure. The light beam P6-P7-P8 has a first oblique portion P6-P7 and a second oblique portion P6-P8, and the first oblique portion P6-P7 and the second oblique portion P6-P8 have substantially equal lengths, thus Both produce a substantially balanced DEP force.

In this embodiment, the opening direction of the light beam (for example, the opening directions represented by ∠P3-P1-P2, ∠P7-P6-P8, etc.) is not limited, and can be freely adjusted according to actual needs. Moreover, the angle between the oblique direction and the longitudinal direction of the light beam or the angle between the oblique parts (when there are only oblique parts) can vary, for example, between 0 and 180°. The longitudinal or oblique portions of the light beam do not necessarily pass through the center point of one or more transistors. Furthermore, in this embodiment, although the light beam may have a transverse portion, it is preferred to use a longitudinal portion, an oblique portion, or a combination thereof to control the movement of the micro-objects.

It should be noted that the terms "transverse", "longitudinal" and "oblique" in the present invention are only used in their relative senses, where "transverse" is perpendicular to "longitudinal", and "oblique" is related to "transverse" and " Vertical" intersection. When a direction is described as "transverse" (or "longitudinal"), directions perpendicular to it are described as "longitudinal" (or "transversal"), and some directions intersecting it are described as "oblique".

In addition, in this embodiment, the third distance D3 is equal to the second distance D2 should be understood as the two are substantially equal, and the two are not necessarily required to be strictly equal. For example, the third distance D3 may be slightly larger than the second distance D2, or the third distance D3 may be slightly smaller than the second distance D2, but the difference between the two is small enough so that the distance between the direction of the third distance D3 and the direction of the second distance D2 equal beam lengths in each direction of no more than about 10 to about 50 (or about 10 to about 40, or about 10 to about 30, or about 10 to about 20, or about 10 to about 15, or about 10) the number of transistors that can be covered within the range of continuous transistors is consistent. Therefore, on the scale of the usual beam length, this difference does not affect the number or area of transistors that the beam can cover in these two directions, thus does not affect the magnitude of the DEP force generated in the two directions.

FIG. 6A shows a schematic structural diagram of a transistor 226 constituting a basic unit of the transistor array of the embodiment shown in FIG. 2 . The transistor 226 is a single hexagonal prism transistor with a hexagonal cross-section. Each phototransistor 226 in the transistor array is formed together by etching the semiconductor material and physically isolated from each other by the insulating material 212 . The insulating material 212 isolating the transistors in all directions is omitted from the figure for clarity. The transistor 226 includes a substrate layer 210 , a collector region 208 disposed on the substrate layer, a base region 206 disposed on the collector region 208 , and an emitter region 205 disposed on the base region 206 . Substrate layer 210 is located at the bottom of transistor 226 . Substrate layer 210 contains N-type dopants in this embodiment. The substrate layer 210 may be a heavily doped region. For example, the doping concentration of the substrate layer 210 is about 10 ¹⁸ cm ⁻³ to about 10 ²¹ cm ⁻³ . The thickness of the substrate layer 210 may be a suitable thickness generally recognized in the art. For example, the thickness of the substrate layer 210 is generally greater than 50 microns, such as about 50 to about 500 microns. The substrate layer 210 may have a resistivity of about 0.001 to about 0.05 ohm·cm.

The collector region 208 is disposed on and in direct contact with the substrate layer 210 . The collector region 208 may have N-type doping. The collector region 208 may be a lightly doped region with respect to the substrate layer 210 . For example, the doping concentration of the collector region 208 is about 10 ¹⁵ cm ⁻³ to about 10 ¹⁸ cm ⁻³ . The thickness of the collector region 208 may be about 100 nm to about 15,000 nm, for example, about 500 nm to about 3,000 nm.

The base region 206 is disposed on the side of the collector region 208 opposite to the substrate layer 210 , and in this embodiment, the base region 206 includes a P-type dopant. A suitable doping concentration may be from about 10 ¹⁶ cm ⁻³ to about 10 ¹⁸ cm ⁻³ . The base region 206 has a suitable thickness, for example, about 100 nm to about 3,000 nm.

The emitter region 205 is disposed on a side of the base region 206 opposite to the collector region 208 . The upper surface of the emitter region 205 constitutes the upper surface of the transistor 226 and is exposed to the microfluidic channel. In this embodiment, the emitter region 205 includes a first doped region 202 and a second doped region 204, wherein the second doped region 204 is adjacent to the base region 206, and the first doped region 202 is disposed in the second doped region Above 204, at least a portion of the first doped region 202 is directly exposed to the microfluidic channel without being covered, eg, by any metal layer, dielectric layer, insulating layer or metal electrode. The insulating covering layer 212 at least partially covers the first doped region 202 . The first doped region 202 and the second doped region 204 have the same doping type, and the first doped region 202 has a higher doping concentration than the second doped region 204 . For example, both the first doped region 202 and the second doped region 204 contain N-type dopants, the first doped region 202 is a heavily doped region N+, and the second doped region 204 is a lightly doped region N− . When both the first doped region 202 and the second doped region 204 contain P-type dopants, the first doped region 202 is a heavily doped region P+, and the second doped region 204 is a lightly doped region P− . The doping concentration of the first doping region 202 may be about 10 to about 10 ⁶ times the doping concentration of the second doping region 204 . For example, the doping concentration of the first doped region 202 may be about 10 ² to about 10 ⁵ times, or about 10 ³ times, that of the second doping region 204 . For example, the doping concentration of the first doped region 202 may be about 10 ¹⁸ cm ^-3 to about 10 ²¹ cm ^-3 , and the doping concentration of the second doping region 204 may be about 10 ¹⁵ cm ^-3 to about 10 ¹⁸ cm ^-3 .

It should be noted that unless otherwise stated, the terms "heavily doped region" and "lightly doped region" and their corresponding symbols are used in the present invention only in their relative sense, that is, when the doped region of a doped region When the impurity concentration is higher than another doping region, the higher doping concentration region is called a heavily doped region, while the lower doping concentration region is called a lightly doped region, and there is no necessary relationship with the absolute value of its actual doping concentration . N-type dopants can be any source of electrons. Examples of suitable N or N+ dopants include phosphorus, arsenic, antimony, and the like. P-type dopants can be any source of holes. Examples of suitable P or P+ dopants include boron, aluminum, beryllium, zinc, cadmium, indium, and the like.

FIG. 3 shows a partial top view of a transistor array of an optical tweezers device 336 according to another embodiment of the present invention. The transistor array of the optical tweezers device 336 includes regularly arranged phototransistors 326 , and the phototransistors 326 are physically isolated by an insulating material 312 (such as SiO ₂ ). Like the phototransistor 226 shown in FIG. 2 , the cross-sectional shape of the phototransistor 326 is also a regular hexagon. The transistors 326 are arranged with a first pitch D1 in the horizontal direction 356 , arranged with a second pitch D2 in the vertical direction 358 , and arranged with a third pitch D3 in the oblique direction. In this embodiment, the first distance D1 is greater than the second distance D2, and the third distance D3 is equal to the first distance D1. In this embodiment, the first distance D1 , the second distance D2 , the third distance D3 , the transverse direction, the longitudinal direction and the oblique direction have the same definitions as those in the embodiment shown in FIG. 2 . Similarly, in this embodiment, the fact that the third distance D3 is equal to the first distance D1 should be understood as being substantially equal, and not necessarily required to be strictly equal.

When the cells are to be driven to move toward the microwell (usually in the longitudinal direction 358 shown in the illustration), the patterned light beam is projected onto the corresponding area of the transistor array, thereby exciting the corresponding transistor, generating a DEP force around the cell, and controlling the movement of the light beam , the cells can be manipulated. For example, light beams Q1-Q2-Q3 may have equal oblique portions Q1-Q3 and lateral portions Q1-Q2. Since the lateral spacing D1 is equal to the oblique spacing D3, the number (or area) of transistors covered by the oblique parts Q1-Q3 of the light beam is equal to the number (or area) of transistors covered by the lateral parts Q1-Q2, for example Both cover adjacent two transistors 326 . Therefore, the transverse DEP force and the oblique DEP force generated by the beam are equal, making it easier to drive the cell to move as expected with a more balanced force, avoiding the deviation between the expected end point and the actual end point.

Similarly, the transistor array has substantially the same arrangement density in the horizontal part and the oblique part (for example, the number of transistors covered by a unit length is basically the same, or the area of transistors covered by a unit length is basically the same). However, this embodiment does not rely on beams Q1-Q2-Q3 having equal oblique portions Q1-Q3 and lateral portions Q1-Q2. When using horizontal and oblique parts with different lengths, since the number or area of transistors covered by a unit length is equal, the number or area of transistors covered by the vertical and oblique parts can be calculated in advance , and thus the DEP force it generates can also be predetermined, and the path along which cells can be moved can thus be predicted.

In addition, the light beam controlling the cell movement does not necessarily have a lateral portion, for example, the light beam may only have an oblique portion, as shown by the light beams Q1-Q3-Q4 in the figure. The light beam Q1-Q3-Q4 has a first oblique portion Q1-Q3 and a second oblique portion Q3-Q4, and the first oblique portion Q1-Q3 and the second oblique portion Q3-Q4 have substantially equal lengths, thus Both produce a substantially balanced DEP force.

Optionally, the light beam can also have one lateral portion and multiple oblique portions, as shown by light beams Q5-Q2-Q1-Q3. The light beam has a first oblique portion Q1-Q3 and a second oblique portion Q2-Q5 and a lateral portion Q1-Q2, which are of equal length. It can be seen that the beam produces equal DEP forces in the first oblique portion, the second oblique portion, and the lateral portion.

As mentioned before, the opening direction of the beam is not limited and can be adjusted freely according to actual needs. Moreover, the included angle between the oblique direction and the transverse direction of the light beam or the included angle between the oblique parts (when there are only oblique parts) can vary, for example, from 0 to 180°. The lateral or oblique portion of the light beam does not necessarily pass through the center point of one or more transistors. In addition, in this embodiment, although the light beam may have a longitudinal portion, it is preferable to use a transverse portion, an oblique portion, or a combination thereof to control the movement of micro-objects.

FIG. 4 shows a partial top view of a transistor array of an optical tweezers device 436 according to another embodiment of the present invention. The transistor array of this embodiment has a transistor arrangement similar to that of the embodiment shown in FIG. 3 , but the cross-section of the phototransistor 426 in this embodiment is circular, so the phototransistor 426 is a cylinder. Similarly, phototransistors 426 are physically isolated by insulating material. The transistors 426 are arranged with the first pitch D1 in the horizontal direction 456 , arranged with the second pitch D2 in the vertical direction 458 , and arranged with the third pitch D3 in the oblique direction. In this embodiment, the first distance D1 is greater than the second distance D2, and the third distance D3 is equal to the first distance D1. In this embodiment, the first distance D1 , the second distance D2 , the third distance D3 , the transverse direction, the longitudinal direction and the oblique direction have the same definitions as those in the embodiment shown in FIG. 2 . Similarly, in this embodiment, the fact that the third distance D3 is equal to the first distance D1 should be understood as being substantially equal, and not necessarily required to be strictly equal.

When the cells are to be driven to move toward the microwell (usually in the longitudinal direction 458 shown in the illustration), the patterned light beam is projected onto the corresponding area of the transistor array, thereby exciting the corresponding transistor, generating a DEP force around the cell, and controlling the movement of the light beam , the cells can be manipulated. For example, light beams T1-T2-T3 may have equal oblique portions T1-T3 and lateral portions T1-T2. Since the lateral spacing D1 is equal to the oblique spacing D3, the number (or area) of transistors covered by the oblique portion T1-T3 of the light beam is equal to the number (or area) of transistors covered by the lateral portion T1-T2, for example Both cover adjacent two transistors 426 . Therefore, the transverse DEP force and oblique DEP force generated by the beam are equal, making it easier to drive the cell as expected with a more balanced force, avoiding the deviation between the expected end point and the actual end point.

Similarly, the light beam can also be T2-T3-T5 or T6-T7-T8, which has a change mode and properties similar to the light beam shown in FIG. 2 , which will not be repeated here.

FIG. 5 shows a partial top view of a transistor array of an optical tweezers device 536 according to another embodiment of the present invention. In this embodiment, the minimum unit constituting the transistor array is a transistor 526 with a triangular cross section, and six transistors 526 form a regular hexagon 560 . The transistor array of this embodiment is obtained by extending the regular hexagon 560 as a repeating unit. In this embodiment, the regular hexagons 560 can be arranged in the manner shown in FIG. 2 or FIG. 3 , so that the horizontal spacing or vertical spacing is equal to the diagonal spacing. The size of the hexagon 560 may be 3 to 10 times, for example 6 times, the size of the regular hexagon shown in FIG. 2 or FIG.

In this embodiment, in the regular hexagon 560, the six triangular transistors 526 are physically isolated from each other, and are arranged such that one side of the hexagon 560 is arranged laterally 556 (and thus the opposite side thereof is also arranged laterally). ). The triangular transistors 526 constituting the hexagon 560 may have the same size, for example, each transistor 526 may have an equilateral triangle or an isosceles triangle in cross section. In other embodiments, the number and shape of triangular transistors 526 may vary as long as the overall hexagonal shape is maintained.

In this embodiment, the six triangular transistors 526 can be formed by two groups of transistors with different orientations. For example, the

transistors

526a, 526c and 526e constitute the first group of transistors, and the

transistors

526b, 526d and 526f constitute the second group of transistors. The two groups of transistors have relative orientation. This positioning method can make the distance between the three

lateral transistors

526b, 526c and 526d equal to the distance between the three

oblique transistors

526d, 526e and 526f inside the hexagon 560 . Therefore, when the beams V1-V2-V3 activate part of the transistors in the hexagon 560, equal photocurrents can be generated in the oblique part V1-V2 and the lateral part V1-V3 because both cover the same number of transistors. Thus, within the hexagon 560, each triangular transistor 526 can be activated independently, so the patterned light beam does not necessarily activate the transistors in units of the hexagon 560.

In addition, in the case of the same charged amount of the conductor and its surrounding environment, the sharper the tip of the conductor, the greater the curvature and the higher the surface charge density, so the stronger the field strength near it, the more obvious the tip effect. On the same conductor, compared with parts with small curvature (such as smooth surface), the part with large curvature (such as edge, edge, corner) is the tip. The angle between the three sides of a triangular phototransistor is smaller than that of a rectangular, hexagonal or circular phototransistor (for example, about 60 degrees), so it is considered that the electric field intensity change is greater at the corner of the transistor than at the center The speed can generate greater DEP force, which is more conducive to the manipulation of micro objects.

FIG. 6B and FIG. 6C respectively show structural diagrams of different sides of the triangular transistor 526 constituting the hexagon 560 . As shown in the figure, the transistor 526 is a triangular prism in a three-dimensional structure, including a substrate layer 510, a collector region 508 disposed on the substrate layer, a base region 506 disposed on the collector region 508, and a base region 506 disposed on the base region 506. The launch area 505 . The emitter region 505 includes a first doped region 502 and a second doped region 504, wherein the second doped region 504 is adjacent to the base region 506, the first doped region 502 is arranged on the second doped region 504, and the first At least a portion of the doped region 502 is directly exposed to the microfluidic channel without being covered, eg, by any metal layer, dielectric layer, insulating layer or metal electrode.

The doping type, doping concentration, thickness, conductivity and other parameters of the substrate 510, the collector region 508, the base region 506, the emitter region 505, the first doped region 502 and the second doped region 504 are the same as those shown in FIG. 6A The corresponding parameters of the transistor 226 are basically similar and will not be repeated here.

Another aspect of the present invention provides a microfluidic device, which includes any transistor optical tweezers device described in the above embodiments of the present invention, an image acquisition system for collecting images in microfluidic channels, and is used to generate light patterns A light pattern generation device, and a control system for controlling the workflow of a microfluidic device.

According to one embodiment, the light pattern generated by the light pattern generating means covers at least two adjacent phototransistors to simultaneously activate the adjacent transistors. The shape of the light pattern can be determined as desired, and typically includes a diagonal length. For example, the light pattern may include a diagonal length and a lateral length, or a diagonal length and a longitudinal length, or a first diagonal length and a second diagonal length, or a combination thereof.

In one embodiment, the oblique length is substantially equal to the lateral or longitudinal length, thereby generating substantially equal photo-induced currents in the oblique direction as in the lateral or longitudinal direction, thereby generating substantially equal DEP forces.

In one embodiment, the microfluidic device does not comprise an electrowetting device, the microfluidic device is thus not used for manipulation of droplets. Therefore, no metal layer, metal electrode, dielectric layer or insulating layer is included on the transistor array, and the emitter region of the transistor array is directly exposed to the microfluidic channel, and is in contact with the medium in the microfluidic channel and the micro objects it contains (such as cells) in direct contact.

The transistor, optical tweezers device and microfluidic device provided by the present invention can be prepared by conventional techniques in the art. Those skilled in the art can manufacture the transistor of the present invention based on the level of the existing semiconductor manufacturing process in combination with the illustrations and descriptions in the specification without special explanation. As an example only, Figure 7 schematically shows a method 700 of fabricating a phototransistor of the present invention.

Method 700 includes step 702, which provides a semiconductor substrate (such as silicon) comprising a doped substrate layer and an undoped layer thereon, the doped substrate layer being used to form the substrate layer in an embodiment of the present invention, the undoped layers are used to form the collector, base and emitter regions in embodiments of the invention.

In step 704, a collector doped layer adjacent to the doped substrate layer is formed on the undoped layer, and the collector doped layer forms the collector region in the embodiment of the present invention. The collector doped layer and the doped substrate layer can be have the same doping type (for example, both are N-type doping), but may have different doping concentrations. For example, the collector doped layer is a lightly doped layer, and the doped substrate layer is a heavily doped layer. The semiconductor material obtained after step 704 comprises a doped substrate layer and a collector doped layer. The shape of each layer (eg, triangle, circle, or hexagon) can be predetermined during IC layout design.

Step 706 forms trenches in the obtained semiconductor material and fills the trenches with an electrically insulating material (eg, SiO ₂ ). The trench penetrates the doped collector layer and extends into the doped substrate layer, thereby forming the insulating barrier in the embodiment of the present invention.

Further, in step 708, a base doped layer is formed in the collector doped layer by ion implantation, and the base doped layer has a different doping type (such as P type doping). By controlling parameters such as time, speed and implantation amount of ion implantation, the thicknesses of the formed base doped layer and collector doped layer can be controlled to meet the requirements for doping concentration and thickness of both.

In step 710, an emitter doped layer is formed in the base doped layer by ion implantation, and the emitter doped layer has a different doping type (for example, N-type doping) from that of the base doped layer. The emitter doped layer can be subjected to independent ion implantation steps to form the first doped layer and the second doped layer with different doping concentrations, for example, the doping concentration of the first doped layer is higher than that of the second doped layer Density, to form the first doped region and the second doped region of the emitter region in the embodiment of the present invention. Similarly, by controlling parameters such as the time, speed and implantation amount of ion implantation, the thicknesses of the first doped layer, the second doped layer, and the base doped layer formed can be controlled, so as to comply with the present invention for the doping of each layer. Concentration and thickness requirements.

Those skilled in the art can predict that in the transistor array of the present invention, the cross-sectional shape of the transistor is not limited to the enumerated circle, triangle or hexagon, after reading the disclosure of the present invention, other shapes (such as ellipse) can be selected. Shape, pentagon, octagon, rectangle or their combination with circle, triangle or hexagon) to realize diagonal and vertical/horizontal proportional transistor arrangement.

In addition, although the doping type and doping level are shown in the embodiments of the present invention and the accompanying drawings, it is well known to those skilled in the art that the illustrated NPN transistor can be replaced by a PNP transistor structure without affecting the scope of the present invention. The realization of the purpose of each embodiment.

The foregoing are all representative examples of embodiments of the present invention, and are provided for illustrative purposes only. The present invention contemplates that one or more technical features used in one embodiment can be added to another embodiment to form an improved or alternative embodiment without violating the purpose of the embodiment. Similarly, one or more technical features used in one embodiment may be omitted or replaced without violating the purpose of the embodiment, so as to form an alternative or simplified embodiment. In addition, one or more technical features used in one embodiment can be combined with one or more technical features in another embodiment to form an improved or alternative implementation. The present invention intends to include all the above improved, replaced and simplified technical solutions.

Claims

A transistor optical tweezers, comprising:

first electrode;

a second electrode electrically connectable to the first electrode;

a phototransistor array disposed between the first electrode and the second electrode, the phototransistor array includes a plurality of bipolar phototransistors, each phototransistor is physically isolated by an insulating element; and

A microfluidic channel arranged between the first electrode and the phototransistor array, the microfluidic channel includes a plurality of micropores, characterized in that,

The plurality of phototransistors are regularly arranged with a first pitch in the lateral direction and a second pitch in the vertical direction, wherein the adjacent transistors located in the adjacent vertical directions are staggered from each other in the lateral direction and the adjacent transistors The direction of the connection line of the center point of the center point constitutes an oblique direction, and the transistors in the oblique direction are arranged at a third pitch, wherein the third pitch is substantially equal to the first pitch or the second pitch.
The transistor optical tweezers according to claim 1, wherein the first pitch is smaller or larger than the second pitch.
The transistor optical tweezers according to claim 1, wherein the plurality of phototransistors are regularly arranged in a circle or a hexagon as a repeating unit.
The transistor optical tweezers according to claim 3, wherein the plurality of phototransistors are regularly arranged in a hexagon as a repeating unit, and the hexagon is formed by a cross section of a hexagonal prism phototransistor.
The transistor optical tweezers according to claim 3, wherein the plurality of phototransistors are regularly arranged with a hexagon as a repeating unit, and the hexagon is composed of six triangles, and the six The triangle consists of six cross-sections of triangular prismatic phototransistors that are physically isolated from each other.
The transistor optical tweezers according to claim 5, wherein the triangles are arranged such that one side of the hexagon is arranged laterally.
The transistor optical tweezers according to claim 3, wherein the plurality of phototransistors are regularly arranged in a circle as a repeating unit, and each circle is formed by a cross section of a cylindrical phototransistor.
The transistor optical tweezers according to claim 1, wherein the plurality of phototransistors are integrated on a common semiconductor substrate, and each phototransistor includes a base region, an emitter region and a collector region.
The transistor optical tweezers of claim 1, wherein the microfluidic channel contains a conductive medium with cells, at least two of the plurality of phototransistors are activated to manipulate the cells.
Transistor optical tweezers according to claim 1, characterized in that the horizontal and oblique light patterns of unit length produce substantially the same intensity photogenerated current in the lateral and oblique directions respectively.
The transistor optical tweezers according to claim 1, characterized in that the longitudinal and oblique light patterns per unit length generate photocurrents with substantially the same intensity in the longitudinal and oblique directions respectively.
The transistor optical tweezers according to claim 1, wherein no metal electrodes are arranged on the surface of the phototransistor array.
A microfluidic device comprising the transistor optical tweezers according to any one of claims 1 to 12, a control system, an image acquisition system and an optical pattern generation device.
The microfluidic device according to claim 13, wherein the light pattern generated by the light pattern generating device covers at least two adjacent phototransistors.
The microfluidic device according to claim 13, wherein the light pattern generated by the light pattern generating device includes an oblique length.
The microfluidic device according to claim 15, wherein the light pattern generated by the light pattern generating device further includes a horizontal length or a vertical length.
The microfluidic device according to claim 16, wherein the oblique length is substantially equal to the transverse length or the longitudinal length.
The microfluidic device of claim 13, wherein the microfluidic device does not include an electrowetting device.