CN207164068U - Biological device - Google Patents

Abstract

A kind of biological device, comprising a catcher, the catcher includes the base board unit of a runner for defining the biofluid circulation that a confession one includes several objects, and a capture unit.The capture unit has several prodgers in the runner, and the trapping layer on the several layers of surface for being separately positioned on the prodger, is acted for the object with the biofluid and limits the object movement.The surface of each prodger weakens the structural strength of the prodger formed with several holes, and is easy to make it separate with the base board unit with external force, thus beneficial to it is quick, advantageously multiple objects being captured are separated from the base board unit.

Description

Biological device

Technical field

A kind of biological device is the utility model is related to, including one more particularly to one kind can be used for including number for one The biofluid circulation of individual object, and catch the biological device of the catcher of the object.

Background technology

People's Republic of China (PRC) patent ZL201621070028.3 discloses a kind of biological particle seizure and acquisition system, Include a trap setting and a capture device.Wherein, the trap setting includes a substrate, and one sets on the substrate Insulating barrier, the insulating barrier has top surface formed with multiple diversion grooves and multiple grooves for defining the diversion groove Bottom surface, and formed with multiple micropores on the top surface of the insulating barrier and the groove bottom.The trap setting is applied to one During an individual liquid corpse or other object for laboratory examination and chemical testing containing multiple target organism particulates, each micropore on the trap setting can house single individual target life Thing particulate.

However, the trap setting disclosed in this Patent Case is applied to catch microorganism cell, human circulation tumour cell When (circulating tumor cells, CTC), work need to be produced with target organism particulate to be coated with the capture device of antibody With and combine, target organism particulate could be taken out, easily make because the force of the capture device is improper target organism microparticle surfaces or It is overall impaired, or failure is captured because adhesion is bad, and it is unfavorable for follow-up observation, analysis with testing again.

Utility model content

The purpose of this utility model is to provide a kind of biofluid circulation for being available for including multiple objects, and can use In the seizure object, and be advantageous to quickly and advantageously completely take out the object being captured, to carry out subsequent treatment Biological device.

Biological device of the present utility model, comprising a catcher, the catcher includes a base board unit and one is caught Catch unit.

The base board unit defines the runner for the biofluid circulation that a confession one includes several objects.

The capture unit has in the runner and from several prodger of base board unit extension, and several sets respectively The trapping layer on the surface of the prodger is put, acts and limits described for the object with the biofluid Object moves.The surface of each prodger is formed with several holes.

Biological device of the present utility model, the prodger can be induced and have charge inducing.

Biological device of the present utility model, the prodger are in array distribution.

Biological device of the present utility model, the surface of each prodger have surrounding from base board unit extension Face, and one connect this around face periphery and for respective trapping layer set basal plane portion.

Biological device of the present utility model, the size range of the described hole of each prodger is 500pm to 50nm.

Biological device of the present utility model, also comprising an electrode unit, the electrode unit has one and is located at the substrate The first electrode of unit.

Biological device of the present utility model, the base board unit have the first substrate of a confession first electrode setting, with And a second substrate for being connected to the first substrate and defining the runner jointly with the first substrate, and the runner has one The individual surface for being formed at the first substrate and the groove housed for the capture unit.

Biological device of the present utility model, the electrode unit also have one located at the of the second substrate of the base board unit Two electrodes.

Biological device of the present utility model, also comprising a separator, for the capture unit to be separated from the base board unit.

Biological device of the present utility model, the separator include one be used for by the prodger of the capture unit shake it is disconnected and The concussion unit separated with the base board unit.

Biological device of the present utility model, also include a signal comprising a signal measurement module, the signal measurement module Measurer and first gold medal for being located on the base board unit of the catcher and being separated and extended along the runner by the runner Belong to conductor and second metallic conductor, each in first metallic conductor and second metallic conductor is conversely set with two Put and for being electrically connected to the signal measuring end of the signal measurer, the signal measurer, which is used for transmitting the catcher, measures news Number, and the measurement signal is received by the feedback signal changed after the catcher, for being analyzed and being counted, it is located at judgement The quantity and species of object in the catcher.

Another purpose of the present utility model is to provide a kind of biofluid circulation for being available for including multiple objects, And can be used for catching the object, and be advantageous to quickly and advantageously completely take out the object being captured, after progress The biological device of continuous processing.

Biological device of the present utility model, comprising a catcher, the catcher includes a base board unit and several points The capture unit of the runner is not arranged at.

The base board unit defines several runners for the biofluid for including a several objects circulation.

Each capture unit has in respective runner and from several prodgers of base board unit extension, and counts The trapping layer on the individual surface for being separately positioned on the prodger, act and limit for the object with the biofluid State object movement in residence processed.The surface of each prodger is formed with several holes.

The beneficial effects of the utility model are：The described hole formed by the prodger surface so that described prominent Go out part structural strength decrease, and after the object is caught, it is easy to directly destroy the prodger with external force, in favor of inciting somebody to action The object being captured departs from the prodger from the base board unit, is used for subsequent treatment or analysis.

Brief description of the drawings

Fig. 1 is a schematic perspective view, illustrates a seizure of a first embodiment of the utility model biological device The configuration mode of device, an electrode unit and a signal measurement module；

Fig. 2 is an incomplete sectional view, for aiding in illustrating Fig. 1；

Fig. 3 is a broken section enlarged drawing, illustrates a capture unit of a catcher of the first embodiment；

Fig. 4 is a schematic diagram, illustrates the catcher for having captured the first embodiment of object being placed in one Shaken in concussion unit, so that several prodgers in the catcher are broken and departed from from a base board unit by shake；

Fig. 5 is a schematic perspective view, illustrates a seizure of a second embodiment of the utility model biological device Device and an electrode unit；And

Fig. 6 is a schematic diagram, is illustrated in a change aspect of the utility model biological device also comprising a cutting Device, and for being cut to a base board unit of the change aspect.

Embodiment

Refering to Fig. 1, Fig. 2 and Fig. 4, a first embodiment of the utility model biological device includes a catcher 1, one Individual 2, separators 5 of electrode unit, and a signal measurement module 3.

Refering to Fig. 1, Fig. 2 and Fig. 3, the catcher 1 is applied to catch several objects 6 in a biofluid.The life Logistics body is such as, but not limited to the liquid corpse or other object for laboratory examination and chemical testing from animal or plant body, the blood of such as animal, lymph, urine, saliva A corpse or other object for laboratory examination and chemical testing, or tissue extractor liquid of plant etc.；The object 6 is such as, but not limited to specific cell, microorganism or protein, all Such as circulating tumor cell (circulating tumor cells, CTC), the core red blood cell (fetal of fetus in human body Nucleated red blood cells, FNRBC), fetal trophoblasts (trophoblast) cell, virus, bacterium or antigen Deng.The catcher 1 includes 11, capture units 12 of a base board unit, and a flow guiding unit 13.

The base board unit 11 has a first substrate 111, and the of a top surface for being connected to the first substrate 111 Two substrates 112, the first substrate 111 define the runner 10 of a confession biofluid circulation with the second substrate 112 jointly, And the groove 101, one that the runner 10 has a top surface for being formed at the first substrate 111 is formed at the second substrate 112 Bottom surface and the guiding gutter 102 that is connected with the groove 101 of the top surface positioned at the first substrate 111.The first substrate 111 Can be phase same material or unlike material with second substrate 112.The material of the first substrate 111 and the second substrate 112 for example but It is not limited to semi-conducting material or biocompatible material etc..The semi-conducting material is such as, but not limited to silicon (silicon).The biology Biocompatible material is such as, but not limited to dimethyl silicone polymer (Polydimethylsiloxane, PDMS), polymethylacrylic acid Methyl esters (Polymethylmethacrylate, PMMA), or makrolon (Polycarbonate, PC) etc..In first implementation In example, the first substrate 111 is a Silicon Wafer (silicon wafer), and the second substrate 112 is polydimethylsiloxanes Made by alkane.

The capture unit 12 includes being arranged in the groove 101 of the runner 10 and extended from the first substrate 111 several Prodger 121, and the trapping layer 123 on the several layers of surface for being respectively arranged at the prodger 121.The prodger 121 is in battle array Column distribution and generally cylindrical, and there is one to surround face from the first substrate 111 extension on the surface of each prodger 121 Portion 120, and one connect this around periphery of face 120 and the basal plane portion 130 that is set for respective trapping layer 123, it is and described The surface of prodger 121 is formed with several holes 122 for being distributed in this around face 120 and the basal plane portion 130.Described hole 122 size is between 500pm between 50nm.The width of each prodger 121 be less than 2 μm, and aspect ratio for 5 with On.Due to the presence of described hole 122 so that machine of the mechanical strength of the prodger 121 compared to imperforate prodger Tool intensity is weak, and is easy to be destroyed the prodger 121 with external force and made the prodger 121 from the first substrate 111 depart from. To make the prodger 121 be easier to depart from from the first substrate 111, it is preferred that each prodger 121 have 30% to 50% porosity.It is preferred that the prodger 121 has 200m²/cm³To 800m²/cm³Specific surface area (Specific Surface area).Designed by the high-specific surface area of the prodger 121, the prodger 121 can be made with electric charge When object 6 is close, can more be induced with the object 6 the opposite charge inducing of powered charge and be gathered in described The surface of prodger 121, and then enable the capture unit 12 more effectively to attract and limit the object 6 to move.It is described prominent It can be identical material or unlike material to go out part 121 and the first substrate 111, the raw material of single material can also be used to be made. In this first embodiment, the prodger 121 and the material of the first substrate 111 are all silicon.The trapping layer 123 can be with flowing through The object 6 in the biofluid of the runner 10 acts and further limits its movement, make the object 6 because It is attached in the trapping layer 123 and is captured.The trapping layer 123 includes the homologue for being used for acting with the object 6 Matter.The tie substance is selected according to the species or characteristic of the object 6 to be caught.The tie substance is such as, but not limited to Specific antibodies, antigen, victory peptide or protein matter molecule etc..It is preferred that tie substance selection can be producing specially between the object 6 One property is bonded (specific binding) person., can to make the object 6 be easier to limit movement by the trapping layer 123 The predetermined substance that makes the object 6 first and can be acted on the trapping layer 123 is combined, for example, makes the object 6 first With the antibody binding with biotin (biotin), and the tie substance in the trapping layer 123 then may be selected can selectivity combine The streptavidin (streptavidin) of biotin.

The preparation method of the capture unit 12 comprises the steps of：First, it is coated with one layer of photoresistance in the top surface of a Silicon Wafer Layer, and the photoresist layer is carried out photolithographic processes (photolithography), a layer pattern layer is formed, the patterned layer includes It is several to be spaced and make the exposed perforation of section silicon wafer；Second, one layer of silver of sputter (supptering) in the patterned layer Atomic layer；3rd, the patterned layer and the silver atoms layer in the patterned layer are removed, and leave the perforation positioned at the patterned layer Interior silver atoms layer；4th, the silver atoms layer to leave includes hydrofluoric acid (hydrofluoric as Catalytic Layer, collocation Acid) etchant with hydrogen peroxide erodes (etching) to the Silicon Wafer below the silver atoms layer left, and produces The groove of Longitudinal extending and the prodger 121 that shape is in generally long column type is formed between the adjacent groove, and simultaneously in each Prodger 121 forms several holes 122 on face 120；5th, remove the silver atoms layer left；6th, to each prominent The basal plane portion 130 for going out part 121 carries out silanization treatment (silylation), and by for acting with the object 6 Tie substance is coated in the basal plane portion 130 of the prodger 121, and in the basal plane portion 130 of the prodger 121 respectively Form several layers of trapping layer 123.The width of the prodger 121 is defined by the spacing between the perforation.The prodger 121 Length is defined by erosion time and etchant concentration.What deserves to be explained is when extending erosion time, then it may make the etchant The basal plane portion 130 of the prodger 121 is corroded, and several holes 122 are also formed in the basal plane portion 130, then makes to be arranged on The surface area of the trapping layer 123 in the basal plane portion 130 is compared to the seizure being arranged in imperforate basal plane portion 130 The surface area of layer 123 is bigger, therefore the contact area between the trapping layer 123 and the object 6 can be enable to be lifted, and The specific surface area of the prodger 121 can be further improved, assembles more charge inducings, and has and preferably catches effect.This is caught The preparation method for catching unit 12 is not limited with above-mentioned.Using the preparation method, it may be such that the manufactured prodger 121 in array-like fitly Arrangement, and be uniformly distributed in the groove 101 of the first substrate 111 so that the capture unit 12 connects with the biofluid Tactile area is lifted, and reaches good capturing efficiency.

The flow guiding unit 13 includes being positioned apart from prolonging in the guiding gutter 102 of the runner 10 and from the second substrate 112 The multiple conducting elements 131 stretched.Length direction compartment of terrain arrangement of the conducting element 131 along the guiding gutter 102, and it is each The shape of individual conducting element 131 is in generally herringbone, and coordinates jointly and arranged in a herring-bone form, for effectively to flowing through the runner 10 The biofluid produce flow-disturbing effect (Turbulence effect), and avoid flowing through and produced in the biofluid of the runner 10 Generating layer stream (laminar flow) phenomenon.

The electrode unit 2 includes a first electrode 21 located at the bottom surface of the first substrate 111, and one is located at The second electrode 22 of the top surface of the second substrate 112.To make the object 6 towards the institute of the capture unit 12 of the catcher 1 State trapping layer 123 and assemble and reduce non-targeted thing and be deposited in the trapping layer 123, the catcher 1 is flowed through in the biofluid Base board unit 11 the runner 10 when, first electrode 21 is replaced with the second electrode 22 and imposes voltage, the catcher 1 can be made Switch between a trap mode and a non-trap mode.In the trap mode, make the first electrode 21 and second electricity The uneven electric field of an intensity is produced between pole 22, and dielectrophoresis phenomenon occurs in the biofluid (dielectrophoresis) so that the object 6 in the biofluid is attracted with non-targeted thing by dielectrophoretic force, and Moved towards the trapping layer 123 of the capture unit 12 in the groove 101 of the first substrate 111, make to be located at institute The trapping layer 123 and the object 6 for stating the basal plane portion 130 of prodger 121 act on, and make the movement of the object 6 It is restricted and is trapped in the trapping layer 123.In the non-trap mode, make the first electrode 21 and the second electrode 22 Between produce a non-uniform electric field opposite with the trap mode, and make in the biofluid non-targeted thing by reverse dielectrophoretic force Attract, and towards positioned at the second substrate 112 guiding gutter 102 in move, and the object 6 then because with the trapping layer Effect between 123 and be persistently attached in the trapping layer 123.After repeated multiple times switching, you can the object 6 is rich Combine in the trapping layer 123.In the utility model, the frequency that the voltage alternately switches can be according to the grain of the object 6 Footpath size is adjusted, and is acted on the time for alloing the object 6 to have abundance with the trapping layer 123, and effectively It is enriched in the trapping layer 123.In a change aspect of the present embodiment, to make the object 6 towards the catcher 1 The trapping layer 123 of capture unit 12 assemble, the second electrode 22 of the electrode unit 2 is non-for necessity, and by supplying power to The first electrode 21 so that the first substrate 111 and the capture unit 12 are influenceed and electric polarization (electric by extra electric field Polarization), and and then produce electric dipole moment (electric dipole moment) attract it is powered in the biofluid The object 6 of lotus so that the object 6 is trapped in the trapping layer 123.

The signal measurement module 3 includes being arranged on the first substrate 111 of the base board unit 11 and respectively along the runner First metallic conductor 31 and second metallic conductor 33 for 10 both sides extension, and one electrically connect first metal and lead The signal measurer 32 of body 31 and second metallic conductor 33.First metallic conductor 31 has two opposite signal measuring ends 311.Second metallic conductor 33 has two opposite signal measuring ends 331.First, it is not applied to the biology in the biological device During fluid, by the signal measurer 32, via to one of signal measuring end 311 of first metallic conductor 31 and this One of signal measuring end 331 of two metallic conductors 33 provides one and measures signal, and receives and come from first metallic conductor 31 Another signal measuring end 311 and second metallic conductor 33 another signal measuring end 331 output feedback signal, And background signal data are used as using the feedback signal.Then, after the biological device is applied to the biofluid, above-mentioned mistake is repeated Journey, and receive the feedback of the signal measuring end 311,331 from first metallic conductor 31 and second metallic conductor 33 Signal, and change signal data is used as using the feedback signal.The change signal data is deducted into the background signal data, obtains one Substantive signal data, while the object 6 to being captured carries out immunofluorescence dyeing (immunofluorescence Staining), help with fluorescence microscope (fluorescence microscope) observation obtain the quantity of the object 6 with Species.With reference to the quantity and species of substantive signal data and the object 6, database is established.When using the biological device After catcher 1 catches the object 6, it can be entered by the catcher 1 that this signal measurement module 3 has the object 6 to seizure Row is measured and obtains change signal data, and the change signal data is compared into the database, you can precisely and rapidly to quilt The object 6 caught is analyzed and counted, and be not necessary to expend again time and cost by immunostaining analyzed and in terms of Number.In this first embodiment, the signal measurer 32 is a vector network analyzer (vector network Analyzer, VNA), and measurement signal is used as using differential signal (differential signaling).

Refering to Fig. 4, the separator 5 is disconnected for the prodger 121 of the capture unit 12 to be shaken including one, and makes institute State the concussion unit 51 that prodger 121 separates with the base board unit 11.In this first embodiment, the concussion unit 51 is one Individual ultrasonic vibrating pond.Due to having described hole 122 in the prodger 121 so that the machine in the structure of prodger 121 Tool intensity is weaker, thus destroys its structure easily by external force ultrasonic vibrating, and then it is departed from from the base board unit 11.

Refering to Fig. 1 and Fig. 4, when the utility model biological device is applied into the biofluid, the biofluid along this The runner 10 that base board unit 11 defines circulates, and the biofluid that the flow guiding unit 13 can pass through the runner 10 is uniform Flowing, to lift the probability that the object 6 in the biofluid contacts with the capture unit 12；Meanwhile alternative supply electricity The voltage of pole unit 2 so that the catcher is switched between trap mode and non-trap mode for more than 1 times so that the quilt of object 6 The trapping layer 123 of the capture unit 12 catches and is enriched in the trapping layer 123；Then the signal measurement module is utilized 3, transmitted for the catcher 1 and measure signal, and the signal by the feedback of catcher 1 is collected, in favor of using the feedback signal Follow-up analysis and counting are carried out for the object 6 being captured；Finally, the multiple prominent of the object 6 will be attached with Go out part 121 and be placed in the ultrasonic vibrating pond of the separator 5 with the first substrate 111 to be shaken so that described to be captured Object 6 separates from the first substrate 111 with the prodger 121, to carry out subsequent treatment or analysis.

It is worth noting that, the runner 10 of the catcher 1 of the utility model biological device is not limited to the first embodiment In the linear single runner 10 of type aspect, and can also be designed to that there are multiple runners 10, or by the company of being designed to of runner 10 The shape of continuous bending increases the length of runner 10, in order to lift capturing efficiency.

Refering to Fig. 5, in a second embodiment of the present utility model, the catcher 1 defines several streams including one The base board unit 11 in road 10 and several capture units 12 for being respectively arranged at the runner 10.

Refering to Fig. 6, change at one of the present utility model in aspect, in addition to cutting positioned at the upstream of separator 5 Cutter 4, for being cut to the base board unit 11, the part substrate unit 11 for being attached with the object 6 is captured, to keep away Exempt from the base board unit 11 of remainder and the non-targeted thing of residual produces unwanted fragment or miscellaneous in ultrasonic vibrating pond Matter, the object 6 to be collected is polluted, and then recycle the separator 5, make the prodger 121 and the base board unit 11 separation.The cutter 4 is such as, but not limited to UV laser cutters.

In summary, the utility model biological device is by being formed in the prodger 121 of the capture unit 12 Described hole 122, the mechanical strength of the prodger 121 can be caused to weaken, thus the target is being caught using the catcher 1 After thing 6, can easily with separator 5 by the prodger 121 together with the object 6 being captured in the lump from the base board unit 11 separation；In addition, using the signal measurement module 3, signal measurement can be carried out for the catcher 1, in favor of to being trapped in The object 6 in the catcher 1 is analyzed and counted, so can reach the purpose of this utility model really.

Only as described above, embodiment only of the present utility model, implements when that can not limit the utility model with this Scope, i.e., all simple equivalent changes and modificationss made according to the utility model claims book and description, all still Belong to the scope of the utility model.

Claims (12)

1. a kind of biological device, it is characterised in that include：

One catcher, including

One base board unit, define the runner for the biofluid circulation that a confession one includes several objects；And

One capture unit, has

Several prodgers, extend in the runner and from the base board unit, and the surface of each prodger is formed with several holes Hole, and

Several trapping layer, the surface of the prodger is separately positioned on, and for being produced with the object of the biofluid Act on and limit the object movement.

2. biological device according to claim 1, it is characterised in that：The prodger can be induced and have induced electricity Lotus.

3. biological device according to claim 1, it is characterised in that：The prodger is in array distribution.

4. biological device according to claim 1, it is characterised in that：The surface of each prodger has one from the base Slab element extension surrounds face, and one connects this around periphery of face and for the basal plane portion of respective trapping layer setting.

5. biological device according to claim 1, it is characterised in that：The size range of the described hole of each prodger For 500pm to 50nm.

6. biological device according to claim 1, it is characterised in that：The biological device also includes an electrode unit, should Electrode unit has a first electrode for being located at the base board unit.

7. biological device according to claim 6, it is characterised in that：There is the base board unit confession first electrode to set The first substrate put, and second base for being connected to the first substrate and defining the runner jointly with the first substrate Plate, and the runner has a surface for being formed at the first substrate and the groove housed for the capture unit.

8. biological device according to claim 7, it is characterised in that：The electrode unit also has one and is located at the substrate list The second electrode of the second substrate of member.

9. biological device according to claim 1, it is characterised in that：The biological device also includes a separator, for inciting somebody to action The capture unit separates from the base board unit.

10. biological device according to claim 9, it is characterised in that：The separator includes one and is used for the capture unit Prodger shake is disconnected and the concussion unit that is separated with the base board unit.

11. according to the biological device any one of claim 1 and 8, it is characterised in that：The biological device is also comprising a news Number measurement module, the signal measurement module include a signal measurer and are located on the base board unit of the catcher and by this Runner separate and along the runner extend first metallic conductor and second metallic conductor, first metallic conductor and There are each in second metallic conductor two to be reversed and be measured for being electrically connected to the signal of the signal measurer End, the signal measurer, which is used for transmitting the catcher, measures signal, and receives the measurement signal by changing after the catcher Feedback signal, for being analyzed and being counted, to judge the quantity and species of the object in the catcher.

12. a kind of biological device, it is characterised in that include：

One catcher, including

One base board unit, define several runners for the biofluid for including a several objects circulation；And

Several capture units, the runner is respectively arranged at, and each capture unit has

Several prodgers, extend in respective runner and from the base board unit, and the surface of each prodger is formed with number Individual hole, and

Several trapping layer, the surface of the prodger is separately positioned on, and for being produced with the object of the biofluid Act on and limit the object movement.