CN206096142U - Biological particle is caught and capture system - Google Patents

Abstract

The utility model discloses biological particle is caught and capture system, a trapping apparatus include and establish on a base plate and be formed with the insulating layer that a plurality of ranges are a fish bone structure's diversion grooves on its top surface, this insulating layer still this top surface with but diversion grooves's tank bottom face is formed with the micropore of a plurality of difference holding single target biological particles. Bearing the weight of when one and flowing through this top through a computer electrofluid drive unit's drive when surperficial in the top of this insulating layer surface and the liquid corpse or other object for laboratory examination and chemical testing that contains the multiple targets biological particle, the single target biological particle that comes from this liquid state corpse or other object for laboratory examination and chemical testing is caught easily to each micropore. When one installed carrier that divide to annotate the most advanced of ware and coating and have the antibody that can combine with this target biological particle at a trace and is close to each micropore, this target biological particle was caught through breaking away from this liquid state corpse or other object for laboratory examination and chemical testing with this antibody fixation to this micropore, can be be effectively just captured out the target biological particle that contains in the liquid corpse or other object for laboratory examination and chemical testing with one by one mode easily to sharp follow -up analysis.

Description

Biological particle catches and acquisition system

Technical field

This utility model relates to the seizure of biological particle and captures, and particularly relates to for catching from a liquid corpse or other object for laboratory examination and chemical testing Catch and acquisition system with the biological particle for capturing single target organism microgranule.

Background technology

Cancer is one of topmost cause of death of the mankind now, although the formation machine of cancer turns not yet by fully Solution, but in recent years the transfer (metastasis) of cancerous cell has been considered the one of the main reasons of Cancer death.However, cancerous cell Can constantly hypertrophy (proliferate) and can be via lymphsystem (lymphatic system) or vascular system (vascular system) is transferred to other body parts, this kind of to be followed in human body by lymphsystem or vascular system The cancerous cell of ring is referred to as circulating tumor cell (circulating tumor cells, CTC).

The detection of circulating tumor cell in recent years has become one of important directions for the treatment of of cancer research, has used now Different technologies includes the analysis of flow-type cell measurement, cell filtration and immunomagnetic beadses point capturing circulating tumor cell From method, wherein magnetic activated cell seperation is detection method relatively conventional at present.In short, the detection method is first to contain one Multiple magnetic beads containing the specific antibodies that can be combined with the target cell are added in a corpse or other object for laboratory examination and chemical testing for multiple target cells, and treats the inspection After target cell in body is combined with the specific antibodies on the magnetic bead, collection is combined with the magnetic bead of the target cell, To reach the purpose of cell sorting.However, because the specific antibodies on each magnetic bead can be combined with multiple target cells simultaneously, and And the target cell combined with the specific antibodies is stacked into each other one, therefore, it is difficult to the target of will be stacked into Cell singly separates and captures, with sharp subsequent analysis.

Therefore, how to improve disadvantages mentioned above, the theme further to be inquired into of this case is become then.

The content of the invention

The purpose of this utility model is that offer is a kind of can catch from the liquid corpse or other object for laboratory examination and chemical testing containing multiple target organism microgranules Catch and caught and acquisition system with the biological particle for capturing single target organism microgranule.

This utility model biological particle catches and acquisition system, examines for a liquid containing multiple target organism microgranules Body, and be operable in a trap mode and an acquisition pattern, the biological particle catch with acquisition system comprising a trap setting with And a capture device.The trap setting includes a substrate, an insulating barrier and a microelectromechanical fluid driver element.The insulating barrier sets On the substrate, and with a top surface, the top surface is formed with multiple diversion grooves of the arrangement in a fish bone structure, the insulation Layer also has multiple groove bottoms for defining the diversion groove respectively, and the top surface and each groove bottom of the insulating barrier are distinguished Multiple micropores are formed with, each micropore is formulated for that single target organism microgranule can be housed, the liquid corpse or other object for laboratory examination and chemical testing can be allowed to drop On a region without any diversion groove or micropore of the top surface of the insulating barrier.The microelectromechanical fluid driver element is included One electrod-array for being located at the substrate and the insulation interlayer and a control circuit for electrically connecting the electrod-array.When the biology it is micro- Grain catches and is operated in the trap mode with acquisition system, and the microelectromechanical fluid driver element is applied to this by the control circuit The control mode of multiple voltages of electrod-array driving the liquid corpse or other object for laboratory examination and chemical testing on the top surface of the insulating barrier, with an institute Be intended to flow velocity flow towards the diversion groove so that by the microelectromechanical fluid driver element driving and the water conservancy diversion it is recessed The liquid corpse or other object for laboratory examination and chemical testing of the guide functions of groove, one flow direction is intended to, and flows through the micropore, so that each micropore is easily captured From single target organism microgranule of the liquid corpse or other object for laboratory examination and chemical testing.The capture device includes a micro dispenser, the micro dispensing utensil Have one tip and one be arranged on the sophisticated carrier, the carrier have one be coated with can be combined with the target organism microgranule resist The outer surface of body.When the biological particle catches to be operated in the acquisition pattern with acquisition system, the micro dispenser is actuated to So that the carrier is be close to each micropore, thus the target organism microgranule Jing that captured of the micropore be coated on the carrier should The antibodies on outer surface and attach on this carrier, and cause the carrier away from the micropore, so that attaching in the carrier The target organism microgranule depart from the liquid corpse or other object for laboratory examination and chemical testing.

It is preferred that each diversion groove has an arrow shaped, and the direction indicated by the diversion groove is used as the institute It is intended to flow direction.

It is preferred that the microelectromechanical fluid driver element is using dielectric wetness technique, to drive the liquid corpse or other object for laboratory examination and chemical testing Period moves.

It is preferred that the carrier includes a magnetic bead group.

It is preferred that the substrate is formed with multiple telltale marks for exposing；And the capture device also comprising one be used for supporting and The driver element of the mobile micro dispenser, it is micro- with each that the driver element reaches the carrier according at least to the telltale mark Positioning between hole.

It is preferred that the substrate is the one of which of a printed circuit board (PCB) and a glass plate.

It is preferred that the substrate be by silicon, polymethyl methacrylate (PMMA) and polymethyl siloxane (PDMS) wherein Made by one.

The beneficial effects of the utility model are：The diversion groove that there is provided by the trap setting simultaneously coordinates this micro- Electro-mechanical fluid driver element driving the liquid corpse or other object for laboratory examination and chemical testing to flow through the micropore so that each micropore of the insulating barrier can effectively and Easily capture the single target organism microgranule from the liquid corpse or other object for laboratory examination and chemical testing.On the other hand, provided by the capture device The carrier on the antibody come single target organism microgranule being captured with reference to each micropore, can effectively and easily by The contained target organism microgranule is subtracted out in the way of one by one in the liquid corpse or other object for laboratory examination and chemical testing, with sharp subsequent analysis.

Description of the drawings

Fig. 1 is a block chart, illustrates that this utility model biological particle catches the part unit with an embodiment of acquisition system The operative relationship of part；

Fig. 2 is a schematic top plan view, illustrates a trap setting of the embodiment；

Fig. 3 is a generalized section taken along III-III lines in Fig. 2 of the trap setting of the embodiment；And

Fig. 4 is a schematic diagram, illustrates a capture device of the embodiment.

Specific embodiment

Below in conjunction with the accompanying drawings and embodiment is described in detail to this utility model.

Refering to Fig. 1, this utility model biological particle catches and includes a trap setting 1 with an embodiment of acquisition system 100 And a capture device 2.It is the liquid containing multiple target organism microgranules for one that the biological particle is caught with acquisition system 100 A corpse or other object for laboratory examination and chemical testing, for example, the liquid corpse or other object for laboratory examination and chemical testing can be the body fluid corpse or other object for laboratory examination and chemical testing (blood, lymph fluid, saliva, urine etc.) for coming from animal, but not Here is limited, and the target organism microgranule can be specific cell [such as circulating tumor cell (circulating tumor Cells, CTC), fetus have core red blood cell (fetal nucleated red blood cells, FNRBC)], virus or Antibacterial.In other embodiments, the liquid corpse or other object for laboratory examination and chemical testing may also be one from plant a liquid corpse or other object for laboratory examination and chemical testing.

Please refer to Fig. 2 and Fig. 3, the trap setting 1 includes that a substrate 11, an insulating barrier 12 and a microelectromechanical fluid drive Moving cell 13 (Fig. 2 and Fig. 3 is not shown).

In this embodiment, the printed circuit board (PCB) or a glass plate of a substrate 11 for example, rectangle, but system not subject to the limits. In other embodiments, the substrate 11 also can be by silicon, polymethyl methacrylate (PMMA) or polymethyl siloxane (PDMS) institute Make.

The insulating barrier 12 is located on the substrate 11, and with a top surface 121, the top surface 121 is formed with multiple leading Stream groove 123, each diversion groove 123 has an arrow shaped.In the present embodiment, as shown in Fig. 2 the diversion groove 123 For example may be logically divided into second group that first group and one of two groups, i.e., one above Fig. 2 is located at below Fig. 2, but not as Limit.Per group of diversion groove 123 is arranged in a fish bone structure, and indicates same direction, i.e., first group diversion groove 123 is indicated A such as right direction in Fig. 2, and second group of diversion groove 123 indicates the left direction in such as Fig. 2, but not with this It is limited.In other embodiments, the top surface 121 of the insulating barrier 12 is designed to be formed with singly a group or more groups of leading Stream groove 123.It is preferred that the top surface 121 of the insulating barrier 12 is coated with Succ-PEG-DSPE (Streptavidin).

Additionally, the insulating barrier 12 also has multiple groove bottoms 122 for defining the diversion groove 123 respectively, and at this Top surface 121 is respectively formed with multiple micropores 124 arranged in the way of a such as rule with each groove bottom 122, it is concrete and Speech, the micropore 124 is formed in the region of the non-category diversion groove 123 of the top surface 121, is also formed in the correspondence of diversion groove 123 Groove bottom 122 on.It should be noted that each micropore 124 is formulated for having one can house single target organism microgranule Size.For example, when the target organism microgranule is circulating tumor cell, the diameter of each micropore 124 can be in such as one 10 μ In m to 30 μm of scope, and when the target organism microgranule is virus, the diameter of each micropore 124 can be such as 200nm.Value Obtain it is noted that in order to clearly show the diversion groove 123 and the micropore 124, the water conservancy diversion in Fig. 2 and Fig. 3 is recessed Groove 123 is dimensionally all presented with the micropore 124 in the microcosmic mode relatively exaggerated.

Furthermore, in the present embodiment, the substrate 11 has a top surface 110, and the face of the top surface 110 of the substrate 11 Product more than the insulating barrier 12 area so that the top surface 110 of the substrate 11 have one not by the insulating barrier 12 cover it is outer Dew part, and the exposed parts of the top surface 110 of the substrate 11 are formed with multiple telltale marks 111.In the present embodiment, should The exposed parts of the top surface 110 of substrate 11 are formed with four for example cross telltale marks 111, but are not limited.

The microelectromechanical fluid driver element 13 includes an electrod-array 131 being located between the substrate 11 and the insulating barrier 12, And one electrically connect the electrod-array 131 control circuit 132.The electrod-array 131 for example includes 2 × 6 metal electrodes 1311, but be not limited.The control circuit 132 is for each metal electrode 1311 applies using control mode known to One corresponding voltage.It should be noted that in the present embodiment, the control circuit 132 is, for example, to be electrically connected in external mode The electrod-array 131.However, in other embodiments, the control circuit 132 can be integrated circuit, and can be integrated in this In substrate 11.

For example, the microelectromechanical fluid driver element 13 can utilize dielectric moistening (electrowetting-on- Dielectric, EWOD) technology, but be not limited, come for any liquid of the top surface 121 for being carried on the insulating barrier 12 Body carries out flowing manipulation.It is therefore not necessary to using additional pump, you can so that being carried on appointing for the top surface 121 of the insulating barrier 12 What liquid is moved in driving period.

Refering to Fig. 4, the capture device 2 includes that a micro dispenser 21 and is used to support and the mobile micro dispenser 21 driver element 22.

The micro dispenser 21 has one sophisticated 211 and one carrier 212 for being arranged on the tip 211.In the present embodiment In, a carrier 212 for example, magnetic bead group, but system not subject to the limits.The carrier 212 has an outer surface 213, the outer surface 213 It is coated with the antibody 214 that can be combined with the target organism microgranule, such as epithelial cell adhesion molecule (Epithelial cell Adhesion molecule, EpCAM), but system not subject to the limits.

In the present embodiment, the driver element 22 is for example used for driving the drive module of the micro dispenser 21 comprising one 221st, an image acquisition module 222 and a positioning control module 223 (see Fig. 1).The image acquisition module 222 is for capturing example Such as the top surface 121 comprising the insulating barrier 12 and the micro-imaging of the telltale mark 111.The positioning control module 223 The drive module 221 and the image acquisition module 222 are electrically connected, and receives the image from the image acquisition module 222.Should Positioning control module 223 controls the drive module 221 according to the image, every with the insulating barrier 12 to reach the carrier 212 Positioning between one micropore 124.

The biological particle catches can be used to implement this utility model for the biology of the liquid corpse or other object for laboratory examination and chemical testing with acquisition system 100 Particle capture and acquisition method, and catch according to the biological particle and acquisition method, can sequentially operate in a trap mode and Acquisition pattern.

In the trap mode, first, the liquid corpse or other object for laboratory examination and chemical testing is allowed to drop in a nothing of the top surface 121 of the insulating barrier 12 The region of any diversion groove 123 or micropore 124, such as the upper left corner area shown in Fig. 2, but be not limited.This is micro electronmechanical Fluid drives unit 13 can pass through the control mode that the control circuit 132 is applied to the voltage of the electrod-array 131, for example EWOD control modes driving the flowing of the liquid corpse or other object for laboratory examination and chemical testing, with one desire flow velocity first flow towards first group of diversion groove 123 (flowing to the right of Fig. 2).Due to the water conservancy diversion and the microelectromechanical fluid driver element 13 of first group of diversion groove 123 Fluid drives are controlled, and the liquid corpse or other object for laboratory examination and chemical testing can uniformly flow through first group of diversion groove 123 until the insulating barrier 12 for example shown in Fig. 2 The top surface 121 right side (region without any diversion groove 123).Afterwards, drive likewise by the microelectromechanical fluid The fluid drives control of moving cell 13, makes the liquid corpse or other object for laboratory examination and chemical testing then flow (i.e. to Fig. 2's towards second group of diversion groove 123 Flow left), and plus the water conservancy diversion of second group of diversion groove 123, so that the liquid corpse or other object for laboratory examination and chemical testing can flow uniformly through this second group Diversion groove 123.Finally, the liquid corpse or other object for laboratory examination and chemical testing can flow to a lower left corner of the top surface 121 of the insulating barrier 12 shown in such as Fig. 2 Region (without any diversion groove 123 or micropore 124).

It should be noted that during the flowing of the liquid corpse or other object for laboratory examination and chemical testing, due to performed by the microelectromechanical fluid driver element 13 Such as dielectric moistening (EWOD) control, the liquid corpse or other object for laboratory examination and chemical testing moves in driving period, whereby avoiding the laminar flow of the liquid corpse or other object for laboratory examination and chemical testing Situation and reduction depositional phenomenon.Therefore, the liquid corpse or other object for laboratory examination and chemical testing can flow uniformly through the micropore 124, so that each micropore 124 holds Easily capture the single target organism microgranule from the liquid corpse or other object for laboratory examination and chemical testing.Further, since the bottom of each micropore 124 is coated with chain Mould avidin, can produce affinity interaction with single target organism microgranule being trapped in the micropore 124, so that The target organism microgranule is retained in the micropore 124.

Then, in order to capture the target organism microgranule from each micropore 124, the biological particle catches and acquisition system 100 are operated in the acquisition pattern.

In the acquisition pattern, the micropore 124 for having target organism microgranule is caught for the ease of picking out, selecting can be first sharp With such as immunofluorescence technique (Immunofluorescence technique), but it is not limited, each micropore 124 is caught The single target organism microgranule grasped is to be indicated to distinguish with fluorescence.The acquisition of image acquisition module 222 one is included should Top surface 121 and the micro-imaging of the telltale mark 111 of insulating barrier 12.In the case, the micro-imaging is also included There are multiple image parts for corresponding respectively to target organism microgranule that is described plus indicating fluorescence.The basis of positioning control module 223 From the image of the image acquisition module 222, obtain each of target organism microgranule that is described plus indicating fluorescence relative to The position of the telltale mark 111, and according to the position for being obtained controlling the drive module 221, so that the drive Dynamic model block 221 can be directed at each specific micropore 124 (catching the micropore 124 for having simple target biological particle) with the carrier 212 Positioning mode driving the micro dispenser 21 to move so that the close specific micropore 124 of the carrier 212, and then by applying The antibody 214 of cloth on the outer surface 213 of the carrier 212 is come single mesh being captured with reference to the specific micropore 124 Mark biological particle, and depart from the liquid corpse or other object for laboratory examination and chemical testing and attach on the carrier 212, the trap setting 1 can be captured whereby All target organism microgranules capture from the liquid corpse or other object for laboratory examination and chemical testing in the way of one by one.It should be noted that being picked every time Taking out but attach the target organism microgranule on the carrier 212 can for example soak trypsin via physically or chemically mode (Trypsin) depart from the carrier 212, to obtain single target organism microgranule, programmed with the detection after profit.

In sum, this utility model biological particle catch with acquisition system 100 pass through the trap setting 1 this is micro electronmechanical The guide functions of the driving of fluid drives unit 13 and the diversion groove 123 flow through the micropore driving the liquid corpse or other object for laboratory examination and chemical testing 124, so that the single target organism microgranule from the liquid corpse or other object for laboratory examination and chemical testing can be captured by a micropore 124.Then, picked by this Take the simple target biological particle knot that the antibody 214 on the carrier 212 that device 2 is provided is captured with the micropore 124 Close, the target organism microgranule contained in the liquid corpse or other object for laboratory examination and chemical testing is reached whereby and is subtracted out in the way of one by one, so really In fact the purpose of this utility model can be reached.

Only as described above, is only embodiment of the present utility model, is implemented when limiting this utility model with this Scope, every simple equivalence changes made according to this utility model claim and description and modification all still belong to In the range of this utility model is covered.

Claims (7)

1. a kind of biological particle catches and acquisition system, for the liquid corpse or other object for laboratory examination and chemical testing containing multiple target organism microgranules, and can grasp Make to capture pattern in a trap mode and one, it is characterised in that：The biological particle catches and is included with acquisition system：

One trap setting, including

One substrate；

One insulating barrier, if on the substrate, and with a top surface, it is in a fish bone structure that the top surface is formed with multiple arrangements Diversion groove, the insulating barrier also has multiple groove bottoms for defining the diversion groove respectively, the top surface of the insulating barrier Multiple micropores are respectively formed with each groove bottom, each micropore is formulated for that single target organism microgranule, the liquid can be housed On the region without any diversion groove or micropore that a state corpse or other object for laboratory examination and chemical testing can be allowed to drop in the top surface of the insulating barrier；And

One microelectromechanical fluid driver element, comprising an electrod-array for being located at the substrate and the insulation interlayer and one this is electrically connected The control circuit of electrod-array, when the biological particle catches to be operated in the trap mode with acquisition system, the microelectromechanical fluid Driver element is applied to the control mode of multiple voltages of the electrod-array by the control circuit to drive in the insulating barrier The liquid corpse or other object for laboratory examination and chemical testing on the top surface, with one desire flow velocity flow towards the diversion groove so that be subject to the Microprocessor-based Current The liquid corpse or other object for laboratory examination and chemical testing of the guide functions of the driving of body driver element and the diversion groove, one flow direction is intended to, and is flowed through The micropore, so that each micropore easily captures the single target organism microgranule from the liquid corpse or other object for laboratory examination and chemical testing；And

One capture device, including a micro dispenser, the micro dispenser is arranged on the load at the tip with a tip and one Body, the carrier has an outer surface for being coated with the antibody that can be combined with the target organism microgranule, catch when the biological particle and Acquisition system is operated in the acquisition pattern, and the micro dispenser is driven such that the carrier be close to each micropore, so that should The target organism microgranule Jing that micropore is captured is with the antibodies being coated on the outer surface of the carrier and attaches On the carrier, and the carrier is caused away from the micropore, so that the target organism microgranule attached in the carrier departs from liquid inspection Body.

2. biological particle according to claim 1 catches and acquisition system, it is characterised in that：Each diversion groove has one Arrow shaped, and the direction indicated by the diversion groove is intended to flow direction as the institute.

3. biological particle according to claim 1 catches and acquisition system, it is characterised in that：The microelectromechanical fluid drives single Unit is using dielectric wetness technique, to make the liquid corpse or other object for laboratory examination and chemical testing move in driving period.

4. biological particle according to claim 1 catches and acquisition system, it is characterised in that：The carrier includes a magnetic bead Group.

5. biological particle according to claim 1 catches and acquisition system, it is characterised in that：

The substrate is formed with multiple telltale marks for exposing；And

The capture device also be used to supporting comprising one and the mobile micro dispenser driver element, the driver element according at least to The telltale mark is reaching the positioning between the carrier and each micropore.

6. biological particle according to claim 1 catches and acquisition system, it is characterised in that：The substrate is a printed circuit The one of which of plate and a glass plate.

7. biological particle according to claim 1 catches and acquisition system, it is characterised in that：The substrate is by silicon, poly- first Made by the one of which of base acrylic acid methyl ester. and polymethyl siloxane.