CN211586663U - Biological detection chip - Google Patents
Biological detection chip Download PDFInfo
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- CN211586663U CN211586663U CN202020123703.4U CN202020123703U CN211586663U CN 211586663 U CN211586663 U CN 211586663U CN 202020123703 U CN202020123703 U CN 202020123703U CN 211586663 U CN211586663 U CN 211586663U
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Abstract
The utility model discloses a biological detection chip, including the base member, be provided with on the base member by biological detection chip's rotation center along the radial outside preceding processing chamber, distribution chamber, water conservancy diversion chamber and the reaction chamber that communicates in order, the intercommunication has the voltage limiting return bend between water conservancy diversion chamber and the reaction chamber, and two inboards of the upper end entry in water conservancy diversion chamber have designed a binding off structure to the inboard extension respectively, are equipped with the sample addition mouth on the preceding processing chamber, still are equipped with the exhaust hole of its inside each cavity of intercommunication and external environment on the base member. The biological detection chip has the pressure-limiting bent pipe with the function of the flow control valve, the liquid can be transferred step by step only by controlling the centrifugal rotating speed, an additional fluid control mechanism is not needed, the operation process is simple and easy, manual operation intervention is not needed in the middle process, the workload of testers is reduced, and the detection efficiency is improved.
Description
Technical Field
The utility model relates to a biological detection supporting equipment technical field, in particular to biological detection chip.
Background
At present, the micro-fluidic chip is a hotspot field of the development of the current micro total analysis system, and is a device which takes the chip as an operation platform and completes the whole process including reagent loading, separation, reaction, detection and the like by combining with technologies such as biology, chemistry, drug screening and the like. In recent years, with the rapid development of microfluidic technology, microfluidic chips have the advantages of integrated miniaturization and automation, small reagent volume, high throughput and the like, and play an increasingly important role in the fields of life sciences, analytical chemistry, biomedicine and the like, and are not only directed to the field of conventional biological detection, but also increasingly important in other related fields with special operating environments or operating requirements.
Taking space biomedicine as an example, space microorganisms are a major safety problem in long-term manned space flight, and seriously threaten the life health of spacemen and the long-term safe operation of spacecrafts. The microorganism breeding in the manned spacecraft can pollute the environment, cause infection or illness of astronauts, corrode materials, cause equipment failure, and threaten the ecological safety of the earth if the microorganism with variation in space is brought back to the earth. Therefore, the development of an advanced rapid detection technology for the potential pathogenic microorganisms of the space station is helpful for rapidly finding out the causes when personnel infection and environmental abnormality occur, and the establishment of targeted measures for effective intervention has important significance and value for guaranteeing the physical and mental health of astronauts and the smooth execution of aerospace missions during the in-orbit flight. The technical process of microbial nucleic acid detection in the conventional laboratory comprises sample treatment, nucleic acid extraction, nucleic acid amplification, nucleic acid detection, result analysis and the like, professional personnel are required to be equipped with certain safety protection in the professional laboratory to perform operations such as liquid transfer on different professional instruments, and the conventional liquid operation cannot be performed in the space station due to special environmental requirements such as space microgravity, low power consumption, weight, volume and the like.
The existing microfluidic chip is difficult to integrate with high integration level and less external driving force, most of the micro-fluidic chips need a lot of extra micro pumps and micro valves for integration, equipment and devices for driving the pumps and the valves are complex, the complexity, the manufacturing difficulty and the cost of the microfluidic chip are increased, and the reliability is reduced. For example, CN203750554U discloses a multi-index detection microfluidic chip, but the chip is limited to only providing a detection platform, and can be completed only by providing auxiliary processes such as other instruments for sample pretreatment and the like; CN205797240U discloses a microfluidic chip for fully integrated microfluidic multi-index detection, but the chip has an additional mixing valve structure, and requires additional auxiliary equipment to perform precise operation on the structure, so as to complete the full-flow reaction.
In addition, for general clinical tests or related tests in other biochemical fields, due to the limitation of the current technological development, the degree of integration of chips and related devices required for test and test is low, and the final reaction operation can only be completed generally, a plurality of preposed or main test and test operation procedures can be completed by a large amount of manual operations, the packaging process requirements of related devices are high, and some special devices can realize reasonable control of test and test even by an additional fluid control structure, so that the operation efficiency of the whole test step is restricted, the application environment of the related biochip in the test and test procedures is limited, and adverse effects are also caused on the accurate and efficient operation of the related test and test.
Therefore, how to provide a biological detection chip to reduce manual operations, get rid of the dependence on fluid control structures, improve detection efficiency, and expand application scope is a technical problem that needs to be solved by those skilled in the art.
SUMMERY OF THE UTILITY MODEL
The utility model aims at providing a biological detection chip, this biological detection chip's relevant operation use simple accurate need not with the help of extra fluid control structure, and detection efficiency is high, and application scope is wide, can be used to the biological detection test of space flight microgravity environment.
In order to realize the above purpose, the utility model provides a biological detection chip, which comprises a base bod, be provided with on the base member by biological detection chip's rotation center is along radially outwards preceding processing chamber, distribution chamber, water conservancy diversion chamber and the reaction chamber that communicates in order, the water conservancy diversion chamber with the intercommunication has the voltage limiting return bend between the reaction chamber, two inboards of the upper end entry in water conservancy diversion chamber have one respectively to have a binding off structure to the inboard extension, be equipped with the sample loading mouth on the preceding processing chamber, still be equipped with the exhaust hole of its inside each cavity of intercommunication and external environment on the base member.
Preferably, the length of the closing-up structure is less than half of the width of the diversion cavity.
Preferably, the diversion cavities are sequentially arranged along the circumferential direction of the centrifugal rotation circumference of the biological detection chip or along the extending direction of the involute of the centrifugal rotation circumference of the biological detection chip.
Preferably, a sedimentation cavity is communicated with the downstream of the reaction cavity along the radial direction of the centrifugal rotation circumference of the biological detection chip, and the near rotation center end of the sedimentation cavity is connected with the far rotation center end of the reaction cavity.
Preferably, the middle part of the pressure limiting elbow is a U-shaped pipe section, two ends of the U-shaped pipe section are respectively communicated with a straight pipe section extending along the flow guiding direction of the flow guiding cavity, and a main straight pipe of the U-shaped pipe section and the straight pipe section are relatively inclined.
Preferably, a buffer cavity is communicated between the diversion cavity and the reaction cavity, the pressure limiting elbow is communicated between the buffer cavity and the diversion cavity, and a capillary is communicated between the buffer cavity and the reaction cavity.
Preferably, the distribution chamber is communicated with a plurality of the diversion chambers, each diversion chamber is communicated with one buffer chamber through one pressure limiting elbow, and each buffer chamber is communicated with one reaction chamber through one capillary.
Preferably, an upstream conduit is communicated between the feeding end of the distribution cavity and the pretreatment cavity, and a large-diameter buffer cavity is arranged in the middle of the upstream conduit.
Preferably, a downstream conduit is communicated between the near-rotation center end of the distribution cavity and the near-rotation center end of the pretreatment cavity, and the exhaust hole is arranged on the downstream conduit.
Preferably, the end of the distribution chamber is communicated with a waste liquid chamber.
Preferably, the substrate is provided with a plurality of pretreatment cavities, and each pretreatment cavity is sequentially arranged and communicated from the rotation center of the biological detection chip to the outside along the radial direction.
The utility model provides a biological detection chip's working process as follows:
relevant reagents and test samples required by test detection are added into the pretreatment cavity through the sample adding port, air in the pretreatment cavity is exhausted to the external environment through the exhaust hole, and then the sample adding port is closed. And then the chips are placed into an auxiliary control device for heating temperature control or illumination treatment, after the treatment is finished, a centrifugal rotating device is used for driving the biological detection chip to integrally rotate, so that liquid in the pretreatment cavity flows into the distribution cavity under the action of centrifugal force and respectively enters each flow guide cavity, and meanwhile, gas in the distribution cavity and the flow guide cavities is extruded to enter the pretreatment cavity through a downstream pipeline to achieve air pressure balance. When liquid reaches the diversion cavity at a low flow rate, although the diversion cavity and the reaction cavity are also in a connection state, the pressure limiting elbow forms a valve effect by depending on a self conduction threshold value, and the liquid pressure is smaller than the threshold value of the valve, so that the liquid can be prevented from entering the reaction cavity through the pressure limiting elbow in a non-test state. The closing structure of the flow guide cavity can avoid the mutual interference of reagents stored in the adjacent flow guide cavities in the mixing process. When the centrifugal rotating equipment increases the rotating speed and the pressure of the liquid in the flow guide cavity is greater than the conduction threshold of the pressure limiting elbow, the liquid can enter the reaction cavity to react so as to complete the related biological detection operation. The settling chamber is used for collecting solids after reaction in the upstream reaction chamber 12.
The utility model discloses following beneficial effect has:
1) the biological detection chip has the pressure-limiting bent pipe with the function of the flow control valve, the liquid can be transferred step by step only by controlling the centrifugal rotating speed, an additional fluid control mechanism is not needed, the operation process is simple and easy, manual operation intervention is not needed in the middle process, the workload of testers is reduced, and the detection efficiency is improved;
2) the chip has higher integration level, simple structure and low processing, manufacturing and packaging cost;
3) the chip detection result is accurate and reliable, the operation process is accurate and controllable, the full-automatic nucleic acid extraction and multiple amplification detection of virus or cells in various sample types such as saliva, throat swab, cervical swab and the like can be widely applied, not only can the chip normally work in a ground environment, but also can be applied to microgravity environments such as a space station and the like, and the application range of the product is greatly expanded.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to these drawings without creative efforts.
FIG. 1 is a schematic view of a bioassay chip according to a first embodiment of the present invention;
FIG. 2 is a schematic view of a bioassay chip according to a second embodiment of the present invention;
FIG. 3 is a schematic view of another bioassay chip according to the first embodiment of the present invention;
FIG. 4 is a schematic structural view of a bioassay chip according to a fourth embodiment of the present invention;
FIG. 5 is a cross-sectional view of the internal structure of the bioassay chip according to the present invention;
FIG. 6 is a cross-sectional view of another internal structure of the bioassay chip according to the present invention;
FIG. 7 is a schematic structural view of a bioassay chip having two substrates on one substrate according to the present invention;
FIG. 8 is a schematic structural view of a bioassay chip having three substrates on one substrate according to the present invention;
fig. 9 is a schematic view of a flow guide cavity and a closing-up structure thereof in a portion a of fig. 8;
FIG. 10 is a schematic structural view of a bioassay chip having four substrates on one substrate according to the present invention.
In fig. 1 to 10:
101-substrate, 102-packaging plate, 11-substrate, 110-centrifugal rotation circumferential line, 111-pretreatment cavity, 112-distribution cavity, 113-diversion cavity, 114-sample adding port, 115-upstream conduit, 116-downstream conduit, 117-large-diameter buffer cavity, 118-waste liquid cavity, 119-impurity removing cavity, 12-reaction cavity, 121-buffer cavity, 122-pressure limiting elbow, 123-capillary tube, 124-sedimentation cavity, 13-vent hole and 14-closing structure.
Detailed Description
The core of the utility model is to provide a biological detection chip, this biological detection chip's relevant operation use simple accurate need not with the help of extra fluid control structure, and detection efficiency is high, and application scope is wide.
In order to make the technical field better understand the solution of the present invention, the following detailed description of the present invention is provided with reference to the accompanying drawings and the detailed description.
Referring to FIGS. 1 to 10, FIGS. 1 to 4 respectively show the structures of the bioassay chips according to three embodiments; FIGS. 5 and 6 are sectional views showing the internal structures of two kinds of the bioassay chips, respectively; FIGS. 7, 8 and 10 are schematic views showing the structure of a bioassay chip having two substrates, three substrates and four substrates on one substrate, respectively.
The utility model provides a biological detection chip, including base member 11, be provided with on the base member 11 by biological detection chip's rotation center along the radial outside preceding processing chamber 111 that feeds through in order, distribution chamber 112, water conservancy diversion chamber 113 and reaction chamber 12, the intercommunication has pressure limiting return bend 122 between water conservancy diversion chamber 113 and the reaction chamber 12, two inboards of the upper end entry of water conservancy diversion chamber 113 have one respectively to have to open up the structure 14 to the inboard extension, be equipped with sample addition mouth 114 on the preceding processing chamber 111, still be equipped with the exhaust hole 13 of its inside each cavity of intercommunication and external environment on the base member 11.
It should be noted that, in the bioassay chip provided by the present embodiment, the substrate 11 and each chamber thereof serve as a complete integrated reaction unit, the bioassay chip may further include a substrate 101 for carrying the substrate 11, 1, 2, 3, 4 or more substrates 11 may be disposed on one substrate 101, and the integrated reaction unit represented by each substrate 11 may independently complete a bioassay test, as shown in fig. 7, 8 and 10, which shows a bioassay chip structure in which 2 substrates 11, 3 substrates 11 and 4 substrates 11 are disposed on one substrate 101, respectively. The whole structure of the base plate 101 may be a circle center plate with a center hole, or may be designed into a fan shape, a square shape, an oval shape, or other structures, and when more than two bases 11 are disposed on the base plate 101, the bases 11 are preferably arranged in sequence along the circumferential direction of the centrifugal rotation circumference of the biological detection chip.
When the substrate 101 has a circular plate structure, the diameter thereof is in the range of 40 to 600mm, preferably 60 to 150 mm. The substrate 101 is made of one or a mixture of glass, silicon, metal and polymer, and in principle, any material can be used as long as it can meet the actual use requirement of the bioassay chip.
The scheme can store biological or chemical reagents for sample pretreatment in advance in the pretreatment cavity 111, the storage form of the reagents can be liquid or solid, can be in the form of liquid drops, paste, gel, film, powder and the like, can be one substance or a mixture of a plurality of substances, and can be placed at one or more positions of the pretreatment cavity 111. Preferably, the storage reagent contains components that can be used for sample liquefaction and cell and/or pathogen lysis, and can complete the lysis of cells and/or pathogens contained in the sample under certain conditions (such as 37 ℃ to 95 ℃). The reagent component can include one or more of sodium hydroxide, sodium bisulfate, DTT, TCEP, guanidine isothiocyanate, guanidine hydrochloride, SDS, TritonX-100, Tween-20, CTAB, proteinase k, lysozyme and the like, and one or more of a plurality of auxiliary components, such as excipient, preservative and the like.
According to the scheme, biological or chemical reagents for mixing or reacting with the pretreated sample can be stored in the diversion cavity 113 in advance, and the storage form of the reagents can be drop-shaped, paste-shaped, gel-shaped, film-shaped or powder-shaped, and can be one substance or a mixture of a plurality of substances. Preferably, the reagent contains chemical components which can be used for nucleic acid amplification reaction, including but not limited to one or more of DNA polymerase, RNA polymerase, reverse transcriptase, recombinase, nicking enzyme, nucleic acid repair enzyme, restriction enzyme, magnesium ion, potassium ion, dNTP, rNTP, PEG (400-20000), BSA, TE, betaine and the like, and one or more of a plurality of auxiliary components, such as fluorescent dye, excipient, preservative and the like.
The present solution can store in advance biological or chemical reagents for mixing or reacting with the samples processed before in the reaction chamber 12, wherein the reagents can be stored in the form of drops, paste, gel, film, powder, or a mixture of one or more substances. Preferably, the reagent comprises components for specific nucleic acid amplification reaction or result indication, including one or more sets of oligonucleotide fragments with specific sequences or specific fluorescent labels capable of specifically binding to a certain DNA template, and one or more auxiliary components, such as fluorescent dye, excipient, preservative, etc.
It should be noted that, in actual operation, the above-mentioned storage manner of each reagent may be to directly add a liquid or solid substance into each chamber, or may be to dry and solidify the liquid substance by natural drying, air drying, freeze drying, etc.
Preferably, a sedimentation chamber 124 is communicated with the downstream of the reaction chamber 12 along the radial direction of the centrifugal rotation circumference of the bioassay chip, and the proximal rotation center end of the sedimentation chamber 124 is connected to the distal rotation center end of the reaction chamber 12. The settling chamber 124 is disposed in communication with and downstream of the reaction chamber 12 for collecting solids that are generated after reaction in the upstream reaction chamber 12, so as to collect and treat the solids intensively and avoid interference of the solids on subsequent related reactions.
It should be noted that the near rotation center end described herein refers to an end position of the member closest to the rotation center of the bioassay chip, and the far rotation center end refers to an end position of the member farthest from the rotation center of the bioassay chip.
The shape of the pressure-limiting bent tube 122 in this embodiment may be a circular arc or a smooth curved tube, or may be a polygonal line tube, including but not limited to a U-shaped tube, an S-shaped tube, an Ω -shaped tube, and an L-shaped tube. Preferably, in this embodiment, the middle portion of the pressure-limiting elbow 122 is a U-shaped pipe section, two ends of the U-shaped pipe section are respectively communicated with a straight pipe section extending along the flow guiding direction of the flow guiding cavity 113, and a main straight pipe of the U-shaped pipe section and the straight pipe section are inclined relatively. The flow guiding direction of the flow guiding cavity 113 is the direction in which the flow guiding cavity 113 guides the liquid to flow along the radial direction of the centrifugal rotation circumference of the biological detection chip, and the main straight tubes of the U-shaped tube section are the two side straight tubes parallel to each other in the main body of the U-shaped tube.
The pipe diameter of the pressure limiting elbow 122 is 0.1-1 mm, and the preferred size is 0.2 mm.
Preferably, a buffer chamber 121 is communicated between the diversion chamber 113 and the reaction chamber 12, the pressure-limiting elbow 122 is communicated between the buffer chamber 121 and the diversion chamber 113, and a capillary 123 is communicated between the buffer chamber 121 and the reaction chamber 12. The pressure limiting bent pipe 122 can cooperate with the capillary 123 to realize effective separation and flow limitation of the reagent and the sample between the diversion cavity 113 and the reaction cavity 12, thereby further improving the operation precision and controllability of the related detection reaction, meanwhile, the buffer cavity 121 can effectively buffer the liquid and the like introduced from the diversion cavity 113, and avoid the phenomenon that the high-pressure liquid flowing at high speed generates structural impact on the main structure of the reaction cavity 12 or other phenomena which may generate adverse effects on the reaction process and the detection result, thereby further ensuring the reliability and accuracy of the detection result.
It should be further explained that, in practical application, the purpose of adjusting the corresponding feed conduction threshold of the reaction chamber 12 can be achieved by adjusting and replacing the pressure-limiting bent tube 122 and the capillary tube 123 with different dimensions, so as to meet the requirement of implementing corresponding detection tests for different test materials under different working conditions.
Preferably, the distribution chamber 112 is communicated with a plurality of diversion chambers 113, each diversion chamber 113 is communicated with a buffer chamber 121 through a pressure-limiting elbow 122, and each buffer chamber 121 is communicated with a reaction chamber 12 through a capillary 123. The bioassay chips shown in fig. 1 to 4 each have 10 flow guiding cavities 113 and 10 corresponding reaction cavities 12.
It should be noted that reagent can prestore in the water conservancy diversion chamber 113 in this scheme to from the mixing chamber of the chip among the structural substitution prior art, and then simplify the chip structure, the reagent concentration of prestoring in a plurality of water conservancy diversion chambers 113 can be unanimous, also can be different. The diversion cavity 113 not only has the function of quantifying liquid, but also can quantify the liquid volume more accurately, and moreover, the liquid is distributed into the diversion cavities 113 and can be mixed with the reagent prestored in the diversion cavity 113, and the mixing effect is better than the effect of mixing in one cavity in the prior art.
The diversion cavity 113 may be square, rectangular, triangular, rounded rectangular, semicircular, semi-elliptical, or the like, or may be a combination thereof. The diversion cavities 113 may be the same or different in shape, and may be the same or different in area or volume, so as to achieve uniform or non-uniform distribution and transfer of liquid. The upper opening of the diversion cavity 113 is preferably designed to be in a closed shape, as shown in fig. 8 and 9, two inner sides of the inlet at the upper end of the diversion cavity 113 are respectively designed with a closed structure 14 extending inward, further preferably, the length of the closed structure 14 is less than half of the width of the diversion cavity 113, and by designing the closed structure 14, it can be ensured that mutual interference between adjacent diversion cavities 113 is avoided in the process of liquid flowing into the diversion cavity 113 and in the process of liquid mixing uniformly in the diversion cavity 113.
Preferably, the diversion cavities 113 are sequentially arranged along the circumferential direction of the centrifugal rotation circumference of the bioassay chip or along the extending direction of the involute of the centrifugal rotation circumference of the bioassay chip, and the centrifugal rotation circumferential line 110 of the bioassay chip is shown in fig. 1, 2 and 7. When the diversion cavities 113 are arranged along the involute, the liquid can be more smoothly and uniformly distributed into each diversion cavity 113, that is, the liquid can be more fully distributed in the diversion cavity 113 far away from the upstream conduit 115.
It should be noted that the distribution chamber 112 and the pretreatment chamber 111 may be connected end to end only by a connecting pipeline, or may be connected in a circulating manner by an upstream pipeline and a downstream pipeline.
Referring to fig. 1, in one embodiment, an upstream conduit 115 is preferably connected between the feeding end of the distribution chamber 112 and the pretreatment chamber 111, and a large-diameter buffer chamber 117 is disposed in the middle of the upstream conduit 115. Specifically, the proximal rotation center end of the upstream conduit 115 is connected to the distal rotation center end of the pretreatment chamber 111, so as to transfer all the liquid in the pretreatment chamber 111; the distal rotational center end of the upstream conduit 115 is connected to the feed end of the distribution chamber 112, i.e., the proximal rotational center end of the distribution chamber 112. The inner diameter of the large-diameter buffer cavity 117 is larger than that of the upstream conduit 115, and the large-diameter buffer cavity 117 can moderately buffer, guide and stabilize the pressure of the liquid flow which is introduced into the upstream conduit 115 from the pretreatment cavity 111, so that the liquid flow can be stably and efficiently introduced into a related cavity such as the downstream distribution cavity 112 from the pretreatment cavity 111.
Referring to fig. 1, in the embodiment, it is further preferable that a downstream conduit 116 is communicated between the near rotation center end of the distribution chamber 112 and the near rotation center end of the pretreatment chamber 111, and the exhaust hole 13 is disposed on the downstream conduit 116. The exhaust hole 13 is preferably provided near the rotational center end of the downstream guide pipe 116. During the sample application process, the downstream conduit 116 functions to vent the gas in the pretreatment chamber 111 and the distribution chamber 112 and other related chambers to the external environment through the vent 13; during the centrifugal rotation, the downstream duct 116 and the upstream duct 115 form a complete air circuit circulation to ensure the smooth proceeding of the centrifugal rotation.
As shown in fig. 1, after the sample is added to the front processing chamber 111 through the sample addition port 114, the air in the front processing chamber 111 reaches the downstream conduit 116 through the buffer pool and the channel, which are connected in parallel, and the upstream conduit 115 and the distribution chamber 112, and finally is discharged from the air vent 13, and then the sample addition port 114 is closed with a film-like material having a certain viscosity. The liquid in the pretreatment chamber 111 is driven into the distribution chamber 112 by centrifugal rotation driving force provided by centrifugal rotation equipment such as a rotary motor, and at this time, the liquid in the pretreatment chamber 111 reaches the distribution chamber 112 by breaking the blocking effect of the large-diameter buffer chamber 117 due to the low-speed centrifugal force.
Referring to FIG. 3, FIG. 3 is a schematic structural diagram of another bioassay chip according to the first embodiment of the present invention. The structure of the chip shown in fig. 3 is different from that of the chip shown in fig. 1 in that no necking structure is designed on both sides of the inlet at the upper end of the diversion cavity 113, and the other component structures are the same as those of fig. 1.
Referring to FIG. 2, in another embodiment, the downstream conduit 116 is connected to only the near-rotation center end of the distribution chamber 112 and extends radially toward the rotation center of the bioassay chip, and the near-rotation center end of the downstream conduit 116 is opened with an exhaust hole 13 for exhausting the gas in the distribution chamber 112 and the related chambers.
As shown in fig. 2, after the sample is added to the pretreatment chamber 111 through the sample addition port 114, the liquid in the pretreatment chamber 111 is transferred into the distribution chamber 112 by driving using a kit, and after a short time, the internal air pressure of the pretreatment chamber 111 starts to decrease as the space occupied by the liquid in the pretreatment chamber 111 starts to decrease, and the internal air pressure of the distribution chamber 112 starts to increase as the liquid in the distribution chamber 112 starts to increase, and in this process, although there is no downstream conduit 116 as shown in fig. 1, the increased air pressure of the distribution chamber 112 can be balanced with the decreased air pressure in the pretreatment chamber 111 through the upstream conduit 115, and at this time, the liquid in the distribution chamber 112 increases, the liquid in the pretreatment chamber 111 decreases, and the pressure balance between the two is achieved. Since the driving force is continuously provided, the equilibrium state is continuously changed until the liquid in the pretreatment chamber 111 is completely transferred to the distribution chamber 112, and the final equilibrium is reached. It will be readily appreciated that the magnitude of the liquid driving force is inversely related to the width of the upstream conduit 112. As described above, the driving force is still less than the threshold of the valve formed by the pressure limiting elbow 122, so that the liquid is still distributed in the diversion cavity 113 and does not enter the reaction cavity 12 in advance. A downstream conduit 116 and a vent 13 may also be provided on the distribution chamber 112 on a side thereof near the center of rotation to further facilitate the transfer of the entire liquid in the pretreatment chamber 111 to the distribution chamber 112.
Preferably, the inner surfaces of the pre-treatment chamber 111, the large-diameter buffer chamber 117, the distribution chamber 112, the diversion chamber 113, and the reaction chamber 12 may be wholly or partially physically or chemically treated to be more hydrophobic than the original surface of the substrate material, i.e., a surface hydrophobization treatment. Preferably, the contact angle of the surface with the contained solution after the hydrophobic treatment is 90 ° to 140 °. Preferably, the scheme can also carry out surface hydrophilization treatment on the inner walls of other chambers and pipelines except the chamber wholly or locally so as to adapt to the requirements of related detection tests of different samples or different application environments.
It should be noted that, in practical applications, the reaction chambers 12 are preferably distributed uniformly and equidistantly along the circumferential extension direction of the centrifugal rotation circumference of the bioassay chip, that is, the distance between two adjacent reaction chambers 12 and the rotation center of the centrifugal rotation device is equal, and the central angles corresponding to the arc segments between two adjacent reaction chambers 12 are equal, and the uniform distribution structure can effectively ensure that the reaction rates of the samples and the reagents in the reaction chambers 12 are consistent and the reaction is performed sufficiently.
Preferably, the end of the distribution chamber 112 communicates with a waste chamber 118. Waste fluid generated during the relevant detection test may be passed under centrifugal force through distribution chamber 112 into waste fluid chamber 118 for concentrated collection. The waste liquid cavity 118 is also correspondingly designed with a diversion cavity 113, and the volume ratio of the diversion cavity 113 of the waste liquid cavity 118 to the diversion cavity 113 of the reaction cavity 12 is larger than 2, so as to ensure that enough volume is provided for accommodating redundant liquid. In practical applications, waste liquid chambers 118 may be disposed at two ends of the distribution chamber 112, respectively, to ensure waste liquid collection efficiency. A waste chamber 118 may be provided at only one end of the dispensing chamber 112. Of course, if a plurality of waste liquid cavities 118 are provided, it should be ensured that each waste liquid cavity 118 and each diversion cavity 113 are also arranged along the extending direction of the same arc, so as to ensure the liquid diversion effect.
According to the scheme, pressure limiting communicating pieces such as pressure limiting bent pipes 122 can be arranged between the waste liquid cavity 118 and the flow guide cavity 113 and between the impurity removing cavity 119 and the flow guide cavity 113 so as to reasonably control the conduction threshold of the waste liquid cavity 118, prevent a reagent or a sample which should participate in relevant biochemical reactions of a detection test from mistakenly entering the waste liquid cavity 118, and prevent waste liquid from flowing back into the distribution cavity 112.
Referring to FIG. 4, in the third embodiment, preferably, a plurality of pretreatment chambers 111 are disposed on the substrate 11, and the pretreatment chambers 111 are sequentially arranged and communicated from the rotation center of the bioassay chip to the outside along the radial direction. So set up, can realize the multiple pretreatment step of sample, satisfy some biological assay test demands that need multiple pretreatment such as multiclass reagent or multiclass sample to the test efficiency of the biological detection chip that further improves this scheme and extremely application scope. Of course, the pretreatment chambers 111 may be connected in parallel, and when the centrifugal rotation is performed, the pretreatment chambers 111 transfer liquid to the distribution chamber 112 at the same time, so that the liquid in the pretreatment chambers 111 can be transferred to the distribution chamber 112 more quickly, and the detection efficiency can be improved.
It should be noted that, for different experimental requirements, it is possible to choose to dispose or not dispose the sedimentation chamber 124 at the end of the reaction chamber 12, but whether the sedimentation chamber 124 is disposed or not, in practical applications, it should be ensured that the volume of the diversion chamber 113 is not greater than the sum of the volumes of the downstream chambers corresponding to the sedimentation chamber 124, so as to ensure that the biochemical reactions in the reaction chambers 12 are independent and do not interfere with each other. Specifically, if the end of the reaction chamber 12 is provided with the settling chamber 124, it is ensured that the volume of the diversion chamber 113 is not greater than the sum of the volumes of the corresponding pressure limiting elbow 122, the reaction chamber 12 and the settling chamber 124; if the end of the reaction chamber 12 is not provided with the settling chamber 124, it is ensured that the volume of the diversion chamber 113 is not greater than the sum of the volume of the corresponding pressure-limiting elbow 122 and the volume of the reaction chamber 12; in addition, no matter what kind of structure and operating mode above-mentioned, all should preferably guarantee that the volume of water conservancy diversion chamber 113 is greater than the volume of its corresponding reaction chamber 12 to make the reaction more abundant, the reflection effect is better, and the testing result is more accurate reliable.
It should be noted that the pretreatment chamber 111, the distribution chamber 112, the reaction chamber 12 and their accessories (the buffer chamber 121, the sedimentation chamber 124, the pressure limiting elbow 122, etc.) of the substrate 11 may be respectively located at two sides of the substrate 101 and communicate with each other by means of small holes penetrating through the substrate 101. The main body part of the biological detection chip is a substrate 101, two sides of the substrate 101 are covered with packaging plates 102, a pretreatment cavity 111, a distribution cavity 112, a diversion cavity 113, a reaction cavity 12, a pressure limiting elbow 122 and the like are all positioned between the substrate 101 and the packaging plates 102, and a sample adding port 114 and an exhaust hole 13 are positioned on the packaging plates 102. The inter-plate cavity structure formed by the matching gap between the substrate 101 and the packaging plate 102 can further improve the structural integration level of the biological detection chip, and optimize the tightness and conduction efficiency of the corresponding internal cavity structure, so that the related biological detection reaction is more sufficient and efficient.
It should be noted that, during actual manufacturing, the base plate 101 and the package plate 102 may be packaged and fastened by any method such as hot pressing, gluing, laser welding, ultrasonic welding or screw fastening, so as to ensure the overall sealing effect and the assembling strength of the assembly.
Please refer to fig. 5. In one embodiment, the pre-treatment chamber 111, the reaction chamber 12, and the pressure limiting elbow 122 are located on the same side of the substrate 101, and the distribution chamber 112 and the diversion chamber 113 are located on the other side of the substrate 101. The different-surface staggered arrangement structure can enable a main reaction chamber formed by the pretreatment chamber 111, the reaction chamber 12 and the pressure-limiting bent pipe 122 and a main flow guide chamber formed by the distribution chamber 112 and the flow guide chamber 113 to be relatively independent and respectively packaged, so that the structural tightness and the structural integration of the internal chamber of the biological detection chip are further improved, and the related chambers positioned on different sides of the substrate 101 can be communicated through a guide hole penetrating through the substrate 101, so that the smooth flowing of a reagent and a sample is ensured.
Please refer to fig. 6. In another embodiment, the two sides of the substrate 101 are respectively provided with a pretreatment chamber 111, a distribution chamber 112 and a diversion chamber 113, one side of the substrate 101 is provided with a pressure-limiting elbow 122 and a reaction chamber 12 which are respectively communicated with the diversion chambers 113, and a guide hole penetrating through the substrate 101 is provided to communicate the chambers at the two sides. The two main reaction chambers formed by the pretreatment chamber 111, the reaction chamber 12 and the pressure-limiting bent pipe 122 are arranged on the two sides of the substrate 101, and are respectively communicated with the same downstream main flow guide chamber formed by the distribution chamber 112 and the flow guide chamber 113, so that two different samples or reagents can be respectively placed into the two pretreatment chambers 111 on the two sides of the substrate 101 in practical application and respectively subjected to corresponding pretreatment processes, and after the pretreatment is respectively completed, the samples or reagents are converged into the same downstream reaction chamber 12 to carry out corresponding detection reaction, thereby further improving the application field and working condition adaptability of the biological detection chip, and further improving the operation efficiency and the structure integration degree.
It should be noted that, when only one side of the substrate 101 has a liquid channel, in order to ensure that the biochemical reactions in the reaction chamber 12 are independent and do not interfere with each other, the volume of the diversion chamber 113 should be less than or equal to the sum of the volumes of the reaction chamber 12, the sedimentation chamber 124 and the buffer chamber 121, and preferably greater than the volume of the reaction chamber 12; when the substrate 101 has liquid passages on both sides, also in order to ensure the independence of biochemical reactions in the reaction chamber 12, the sum of the volumes of the flow guide chambers 113 on both sides of the substrate 101 should be equal to or less than the sum of the volumes of the reaction chamber 12, the sedimentation chamber 124 and the buffer chamber 121, and preferably has a volume greater than that of the reaction chamber 12.
The material of the substrate 101 may be one or more of glass, silicon wafer, metal or polymer, and the polymer may be one or more of PDMS (polydimethylsiloxane), PMMA (polymethyl methacrylate), PC engineering plastic, COC (copolymer of cyclo olefin copolymer), PET (Polyethylene terephthalate), COP of japanese pulsatilla, and ABS (Acrylonitrile butadiene Styrene copolymers).
In addition, the outer wall of the base body 11 is covered with a sealing film 103 which is in fit with the feed opening 114 and the exhaust hole 13. The sealing film 103 can reliably seal the feed port 114 and the exhaust hole 13, so that dust or impurities in the external environment are prevented from entering the cavity inside the substrate 11 when relevant biochemical reaction and detection are performed inside the biological detection chip, thereby ensuring the relative sealing and sealing of each cavity and ensuring the accuracy and reliability of relevant test detection results.
It should be noted that, specifically in actual application, in consideration of the operation requirements under different working conditions, the sealing film 103 may be made of a breathable material or a non-breathable material, and the operator may flexibly select the sealing film according to the actual working conditions, which may be satisfied with the actual operation requirements of the bioassay chip in principle.
The utility model provides a biological detection chip's working process as follows:
relevant reagents and test samples required by test detection are added into the pretreatment cavity 111 through the sample adding port 114, air in the pretreatment cavity 111 is exhausted to the external environment through the exhaust hole 13, and then the sample adding port 114 is closed. And then the chip is put into an auxiliary control device for heating temperature control or illumination treatment, after the treatment is finished, a centrifugal rotating device is used for driving the biological detection chip to integrally rotate, so that the liquid in the pretreatment cavity 111 flows into the distribution cavity 112 under the action of centrifugal force and respectively enters each flow guide cavity 113, and meanwhile, the gas in the distribution cavity 112 and the flow guide cavities 113 enters the pretreatment cavity 111 through the downstream guide pipe 116 to achieve pressure balance. After the liquid reaches the diversion cavity 113 at a low flow rate, although the diversion cavity 113 and the reaction cavity 12 are also in a connected state, the pressure limiting elbow 122 forms a valve effect by depending on the conduction threshold of the pressure limiting elbow 122, and the liquid pressure is smaller than the threshold of the valve, so that the liquid can be prevented from entering the reaction cavity 12 through the pressure limiting elbow 122 in a non-test state. When the centrifugal rotating device increases the rotating speed and the pressure of the liquid in the diversion cavity 113 is greater than the conduction threshold of the pressure-limiting elbow 122, the liquid can enter the reaction cavity 12 to react, so as to complete the related biological detection operation.
In actual operation, the specific application method of the biological detection chip is as follows:
1) loading the sample into the pretreatment chamber 111 of the bioassay chip through the sample loading port 114;
2) sealing the sample adding port 114 and the vent hole 13;
3) under the assistance of the corollary equipment, the sample is mixed and reacted with a preset reagent in the pre-processing cavity 111, and meanwhile, a centrifugal rotating device such as a centrifuge and the like can be used for driving the chip to rotate according to needs, or the temperature of each cavity in the biological detection chip is controlled through temperature control equipment;
4) performing low-speed centrifugation on the biological detection chip by using a centrifugal rotation device, transferring the liquid in the step 3) into the distribution cavity 112, and mixing and reacting the liquid with a preset reagent with the aid of a matched device, wherein the rotation of the biological detection chip can be controlled according to needs, or the temperature in each cavity can be controlled;
5) performing high-speed centrifugation on the biological detection chip by using a centrifugal rotation device, and further transferring the liquid in the distribution cavity 112 into each reaction cavity 12;
6) under the assistance of the matched equipment, the liquid reacts with the reagent preset in the reaction cavity 12;
7) and detecting and analyzing the reaction result.
For further understanding of the technical content of the present solution, the following uses the detection of saliva as an example to further illustrate the practical operation of the biological detection chip disclosed in the present invention.
Adding a saliva sample into a pretreatment cavity 111 of the integrated microfluidic chip through a sample port 114, wherein a virus cracking reagent is embedded in the cavity in advance; then heating the biological detection chip (hereinafter referred to as chip) for 1min to 60min (preferably 30min) in a temperature environment of 37 ℃ to 95 ℃ (preferably 65 ℃) through a matched device to obtain a virus nucleic acid extracting solution, centrifuging the virus nucleic acid extracting solution for 10sec to 60sec (preferably 45sec) by using a centrifugal rotating device to rotate the chip at a rotating speed of 100rpm to 3000rpm (preferably 1600rpm), transferring the virus nucleic acid extracting solution into the flow guide cavity 113, and then fully mixing a preset constant-temperature amplification reagent in the flow guide cavity 113 with the virus nucleic acid extracting solution through dissolution and diffusion; then, a centrifugal rotating device is used for rotating the chip at the rotating speed of 4500rpm for centrifugation for 1min, liquid in the diversion cavity 113 is uniformly distributed into each reaction cavity 12, and primers which react with the nucleic acid of the sample in advance are arranged in the reaction cavities 12; and then heating the chip for 30-60 min (preferably 60min) in the temperature environment of 37-95 ℃ (preferably 65 ℃), carrying out constant temperature amplification reaction in the reaction cavity 12, and finally detecting the fluorescence in the reaction cavity 12 in real time by using a matched instrument to obtain a detection result.
It should be noted that the above-mentioned test equipment and environmental parameters are only for achieving the best test detection effect under the general test conditions, and each data parameter is only for illustration, and in the actual operation, considering the difference of different application conditions and the specific test detection requirements, the skilled person can flexibly adjust the specific value of each parameter according to the actual situation, in principle, as long as the specific requirements of the actual biological test detection can be satisfied.
The utility model discloses following beneficial effect has:
1) the biological detection chip has the pressure-limiting bent pipe with the function of the flow control valve, the step-by-step transfer of liquid can be realized only by controlling the centrifugal rotating speed without an additional fluid control mechanism, the operation process is simple and easy, the manual operation intervention is not needed in the intermediate process, the workload of testers is reduced, the test reaction can be synchronously implemented in each reaction chamber, the multiple treatment of related test operation is realized, and the detection efficiency is improved;
2) the chip has higher integration level, simple structure and low processing, manufacturing and packaging cost;
3) the chip detection result is accurate and reliable, the operation process is accurate and controllable, the full-automatic nucleic acid extraction and multiple amplification detection of virus or cells in various sample types such as saliva, throat swab, cervical swab and the like can be widely applied, not only can the chip normally work in a ground environment, but also can be applied to microgravity environments such as a space station and the like, and the application range of the product is greatly expanded.
The above details the biological detection chip provided by the present invention. The principles and embodiments of the present invention have been explained herein using specific examples, and the above descriptions of the embodiments are only used to help understand the method and its core ideas of the present invention. It should be noted that, for those skilled in the art, without departing from the principle of the present invention, the present invention can be further modified and modified, and such modifications and modifications also fall within the protection scope of the appended claims.
Claims (10)
1. The utility model provides a biological detection chip, its characterized in that, includes base member (11), be provided with on base member (11) by the preceding processing chamber (111), distribution chamber (112), water conservancy diversion chamber (113) and reaction chamber (12) that the rotation center of biological detection chip radially outwards communicates in order, water conservancy diversion chamber (113) with intercommunication has pressure limiting return bend (122) between reaction chamber (12), two inboards of the upper end entry of water conservancy diversion chamber (113) have one respectively to the inside binding off structure (14) that extend, be equipped with sample loading mouth (114) on preceding processing chamber (111), still be equipped with exhaust hole (13) of its inside each cavity of intercommunication and external environment on base member (11).
2. The biological detection chip of claim 1, wherein the length of the constriction structure (14) is less than half the width of the flow guide cavity (113).
3. The bioassay chip as set forth in claim 1, wherein said flow guide cavities (113) are arranged in sequence along a circumferential direction of a centrifugal rotation circumference of said bioassay chip or along an extending direction of an involute curve of said centrifugal rotation circumference of said bioassay chip.
4. The biological detection chip according to claim 1, wherein the middle of the pressure limiting elbow (122) is a U-shaped pipe, two ends of the U-shaped pipe are respectively communicated with a straight pipe extending along the flow guiding direction of the flow guiding cavity (113), and a main straight pipe of the U-shaped pipe and the straight pipe are relatively inclined.
5. The biological detection chip as set forth in claim 4, wherein a buffer chamber (121) is connected between the flow guide chamber (113) and the reaction chamber (12), the pressure limiting elbow (122) is connected between the buffer chamber (121) and the flow guide chamber (113), and a capillary (123) is connected between the buffer chamber (121) and the reaction chamber (12).
6. The bioassay chip as set forth in claim 5, wherein said distribution chamber (112) is connected to a plurality of said flow guide chambers (113), each of said flow guide chambers (113) is connected to one of said buffer chambers (121) through one of said pressure limiting bends (122), and each of said buffer chambers (121) is connected to one of said reaction chambers (12) through one of said capillaries (123).
7. The bioassay chip as set forth in claim 1, wherein an upstream conduit (115) is connected between said feeding end of said distribution chamber (112) and said pretreatment chamber (111), and a buffer chamber (117) having a large diameter is provided in the middle of said upstream conduit (115).
8. The bioassay chip as set forth in claim 7, wherein a downstream conduit (116) is connected between a near-rotation center end of said distribution chamber (112) and a near-rotation center end of said pretreatment chamber (111), and said exhaust hole (13) is provided in said downstream conduit (116).
9. The bioassay chip as set forth in claim 1, wherein said distribution chamber (112) is connected at its end portion with a waste liquid chamber (118).
10. The bioassay chip as set forth in claim 1, wherein said substrate (11) is provided with a plurality of said pretreating chambers (111), and each of said pretreating chambers (111) is arranged and communicated in sequence radially outward from a rotation center of said bioassay chip.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202020123703.4U CN211586663U (en) | 2020-01-19 | 2020-01-19 | Biological detection chip |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202020123703.4U CN211586663U (en) | 2020-01-19 | 2020-01-19 | Biological detection chip |
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| CN211586663U true CN211586663U (en) | 2020-09-29 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113324985A (en) * | 2021-06-16 | 2021-08-31 | 博奥生物集团有限公司 | Centrifugal micro-fluidic detection device and centrifugal micro-fluidic detection system |
| CN113600250A (en) * | 2021-07-21 | 2021-11-05 | 华中科技大学 | Chip for micro-channel assisted high-throughput reagent quantitative distribution and analysis |
| CN118028095A (en) * | 2024-03-29 | 2024-05-14 | 中国科学院过程工程研究所 | Nucleic acid detection device |
-
2020
- 2020-01-19 CN CN202020123703.4U patent/CN211586663U/en active Active
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113324985A (en) * | 2021-06-16 | 2021-08-31 | 博奥生物集团有限公司 | Centrifugal micro-fluidic detection device and centrifugal micro-fluidic detection system |
| CN113600250A (en) * | 2021-07-21 | 2021-11-05 | 华中科技大学 | Chip for micro-channel assisted high-throughput reagent quantitative distribution and analysis |
| CN113600250B (en) * | 2021-07-21 | 2023-03-10 | 华中科技大学 | Chip for micro-channel assisted high-throughput reagent quantitative distribution and analysis |
| CN118028095A (en) * | 2024-03-29 | 2024-05-14 | 中国科学院过程工程研究所 | Nucleic acid detection device |
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Effective date of registration: 20240919 Address after: 102206 No. 18, life science Road, Beijing, Changping District Patentee after: CAPITALBIO Corp. Country or region after: China Patentee after: TSINGHUA University Address before: 102206 No. 18, life science Road, Beijing, Changping District Patentee before: CAPITALBIO Corp. Country or region before: China |