WO2022116758A1 - 一种多功能微流控检测芯片 - Google Patents
一种多功能微流控检测芯片 Download PDFInfo
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- WO2022116758A1 WO2022116758A1 PCT/CN2021/127908 CN2021127908W WO2022116758A1 WO 2022116758 A1 WO2022116758 A1 WO 2022116758A1 CN 2021127908 W CN2021127908 W CN 2021127908W WO 2022116758 A1 WO2022116758 A1 WO 2022116758A1
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- B01L3/502723—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by venting arrangements
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- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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- B01F33/3017—Mixing chamber
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- B01L2300/0864—Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
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Definitions
- the invention belongs to the field of in vitro microfluidic detection, in particular to a multifunctional microfluidic detection chip.
- Microfluidic detection chip technology integrates basic operation units such as sample preparation, reaction, separation, and detection in biological, chemical, and medical analysis processes into a micron-scale chip to automatically complete the entire analysis process. It has great potential in biology, chemistry, medicine and other fields.
- the microfluidic detection chip technology in the prior art still has some defects in practical application, such as complex structure, large sample usage, inaccurate detection results, too small volume ratio between the dilution chamber and the sample chamber, production High cost.
- the centrifugal microfluidic detection chip on the market requires a large amount of blood sample, which is not suitable for clinical blood sampling detection of infants, especially newborns and critically ill patients, and lacks effective quality control functions; therefore, it is necessary to develop a centrifugal microfluidic detection chip.
- the detection chip has a simple structure, a small amount of samples can be injected at a time, multiple indicators can be detected in a small volume, the production cost is low, it is suitable for mass production, and the detection results are more accurate.
- the purpose of the present invention is to provide a multifunctional microfluidic detection chip, which can overcome the defects of the existing microfluidic detection chip technology, can reduce the amount of samples and further improve the accuracy of the detection results.
- a multifunctional microfluidic detection chip includes a chip body, and the chip body is provided with a sample injection cavity, a sample quantitative cavity, a sample overflow cavity, a diluent storage cavity, a diluent quantitative cavity, a diluent overflow cavity, Quantitative mixing chamber, reaction chamber and ventilation holes;
- the sample injection chamber can be used to inject the reaction sample to be detected, and is connected to the sample quantitative chamber through the micro-channel, the reaction sample can enter the sample quantitative chamber from the sample injection chamber, and the excess reaction sample enters the sample overflow chamber;
- the diluent storage cavity is connected with the diluent quantitative cavity through the micro-channel, the diluent can enter the diluent quantitative cavity from the diluent storage cavity, and the excess diluent enters the diluent overflow cavity;
- the reaction cavity includes one or more reaction chambers and a sample blank chamber;
- the mixed liquid After the sample in the sample quantitative chamber and the diluent in the diluent quantitative chamber are mixed in the quantitative mixing chamber, the mixed liquid enters the reaction chamber through the microfluidic channel to react with the reaction reagents therein for detection, and the mixed liquid enters the sample at the same time.
- the blank chamber serves as a sample blank to be tested.
- the sample quantitative chamber includes a first sample quantitative chamber and a second sample quantitative chamber.
- the reaction chamber includes several equidistantly distributed reaction chambers.
- the reaction chamber has the same volume as the sample blank chamber.
- the reaction sample in the sample quantitative chamber and the diluent in the diluent quantitative chamber enter the quantitative mixing chamber through microchannel I and microchannel II respectively after mixing; the mixed solution enters the reaction through microchannel III and microchannel IV in turn.
- the chamber and the sample blank chamber; the microfluidic channel I, the microfluidic channel II and the microfluidic channel III respectively include an inflection point which is close to the center of the chip body relative to the corresponding liquid outflow chamber.
- the channel of the sample blank chamber is wider than the channel of the reaction chamber.
- the quantitative mixing chamber and the reaction chamber are respectively communicated with the ventilation holes.
- the quantitative ratio of reaction sample and diluent in the quantitative mixing chamber is less than 1:30.
- the quantitative ratio of the reaction sample to the diluent in the quantitative mixing chamber is 1:50.
- the reaction reagent is lyophilized beads prepared by lyophilization.
- the lyophilized beads have a radius between 0.5mm and 1mm.
- the microfluidic channel between the sample quantitative cavity and the sample overflow cavity is also provided with a sample ventilation channel connected to the outside of the chip, and the microfluidic channel between the diluent quantitative cavity and the diluent overflow cavity is also provided with a diluent ventilation channel. connected to the outside of the chip.
- the chip is a fan-shaped structure.
- the chip also includes a chip upper layer and a chip middle layer, and the chip body is located at the lower layer.
- Each side of the chip body is provided with a splicing card position.
- the chip body can be used to detect biochemical items, immune items, nucleic acid molecule items and blood coagulation items.
- the present invention has the following advantages:
- the quantitative ratio of the reaction sample and the diluent is designed to be less than 1:30, and an appropriate ratio of the reaction sample and the diluent is selected according to the needs.
- a microfluidic detection chip with a fixed structure is designed. In the application, it is only necessary to change the reagent formula required for different detection indicators, and a chip design template can meet the clinical detection of different projects or project combination indicators.
- reaction chambers of the present invention have the same three-dimensional size as the sample blank chamber, so the volume is the same, and the volume of the reaction sample and the diluent entered during the reaction are the same, so only one sample blank chamber needs to be set up to realize several reaction chambers
- the effective quality control of the detection index combination simplifies the chip structure and reduces the cost.
- the sample blank chamber of the present invention is located at the end of the reaction chamber array, shares a micro-channel with the reaction chamber, and can be used as a sample blank chamber and a mixing liquid overflow chamber at the same time, and the sample blank is the reaction sample and the diluent. Mixing the liquid, the test result will eliminate the influence of the sample itself, and the test value of the sample blank can detect whether the amount of the sample and the diluent entering the reaction chamber is sufficient, which has the dual functions of improving the accuracy of the test results and judging the validity of the test.
- the blood collection volume of the present invention is small, only one drop of blood is needed for one injection, and simultaneous detection of multiple indicators can be realized, and the blood sample consumption is only 1/10 to 1/5 of that of ordinary products in the market, and is especially suitable for neonatal and long-term tumors. Clinical detection of patients with difficulty in blood collection due to radiotherapy, chemotherapy and other reasons.
- the chip of the present invention has a fan-shaped structure, and a splicing card position is provided on the left and right edges of the chip for splicing two chips, and the three chips can form a circular chip, which can detect three samples at a time, which can greatly increase the Measure the throughput of the sample.
- FIG. 1 is a schematic diagram of the overall structure of the multifunctional microfluidic detection chip of the present invention.
- FIG. 2 is a schematic diagram of the front structure of the chip body in the multifunctional microfluidic detection chip of the present invention.
- FIG. 3 is a schematic three-dimensional structure diagram of the chip body in the multifunctional microfluidic detection chip of the present invention.
- FIG. 4 is a schematic front view of the overall three-dimensional structure of the multifunctional microfluidic detection chip of the present invention.
- FIG. 5 is a schematic view of the back of the overall three-dimensional structure of the multifunctional microfluidic detection chip of the present invention.
- FIG. 6 is a schematic diagram of the assembled structure of the disc-type multifunctional microfluidic detection chip assembled by the multifunctional microfluidic detection chip of the present invention.
- FIG. 7 is a schematic diagram of the overall structure of a disc-type multifunctional microfluidic detection chip formed by splicing the multifunctional microfluidic detection chip of the present invention.
- the multifunctional microfluidic detection chip of the present invention is manufactured by injection molding of a mold, and can be used with detection equipment.
- the detection chip has a fan-shaped structure, preferably one-third of the circle, that is, the angle formed by the intersection of the left and right extension lines is 120 degrees.
- the fan-shaped structure can be part of the circle, and the rest can be designed and added according to needs part.
- the multifunctional microfluidic detection chip of the present invention includes three layers: upper, middle and lower layers, as shown in FIG. lower chip.
- the upper layer 1 of the chip is provided with a through hole 261 of the upper sample injection chamber, a through hole 262 of the upper diluent storage chamber and a group of through holes 263 of the upper reaction chamber.
- the upper sample injection chamber through holes 261 and the upper diluent storage chamber through holes 262 are located near the center of the upper layer 1 of the chip, and the upper reaction chamber through holes 263 are equally spaced and distributed inside the upper edge of the upper layer 1 of the chip.
- the upper sample injection chamber through hole 261 is used for adding samples, and the upper diluent storage chamber through hole 262 and the upper reaction chamber through hole 263 correspond to the diluent storage chamber 12 and each reaction chamber, respectively.
- the middle layer 2 of the chip is provided with through holes 264 in the middle layer injection chamber, through holes 265 in the middle layer diluent storage chamber, a set of ventilation through holes 266 and a set of positioning hole through holes 267 .
- the through-hole 264 of the middle-layer injection chamber and the through-hole 265 of the middle-layer diluent storage chamber are located near the center of the middle layer 2 of the chip, and correspond to the through-hole 261 of the upper sample injection chamber of the upper layer 1 of the chip and the through-hole 262 of the upper layer of the diluent storage chamber respectively.
- the through hole 266 and the positioning hole through hole 267 are farther from the center of the middle layer 2 of the chip than the through hole 264 of the middle layer injection chamber and the through hole 265 of the middle layer diluent storage chamber.
- I 221 corresponds to the ventilation hole II 222
- the positioning hole through hole 267 corresponds to a group of positioning holes 25 on the lower chip body 3 .
- the chip body 3 is provided with a sample injection chamber 4, a sample quantitative chamber, a sample overflow chamber 11, a diluent storage chamber 12, a diluent quantitative chamber 15, a diluent overflow chamber 16, and a quantitative mixing chamber.
- the cavity 17, the reaction cavity, the ventilation holes I 221 and the ventilation holes II 222, and the chambers are all connected by micro-channels.
- the sample injection chamber 4 and the diluent storage chamber 12 are located near the center of the chip body 3.
- the top of the sample injection chamber 4 is provided with a sample cover 5, and the sample cover 5 is provided with a sample inlet 6, which can be used for injecting the sample to be detected, diluting
- the liquid storage chamber 12 is provided with a diluting liquid bag 13, and a puncturing structure 14 is provided at the bottom for injecting the diluting liquid.
- the sample quantitative chamber includes a first sample quantitative chamber 9 and a second sample quantitative chamber 10.
- the first sample quantitative chamber 9 and the second sample quantitative chamber 10 communicate with the sample injection chamber 4.
- the first sample quantitative chamber 9 and the first sample quantitative chamber The two-sample quantitative chamber 10 is farther from the center of the chip body 3 than the sample injection chamber 4.
- the sample in the sample injection chamber 4 will pass through the bottom port of the sample injection chamber 4 due to the centrifugal effect. It flows through the reverse flow channel, and then flows toward the first sample quantitative chamber 9 and the second sample quantitative chamber 10 through the front flow channel.
- the outlet of the flow channel is located on the side of the first sample quantitative cavity 9 close to the center of the chip body 3;
- the vertical flow channels are connected;
- the bottom surface of the injection cavity 4 is provided with a flow channel sealing film 8 of the injection cavity to prevent the sample from overflowing when it flows through the reverse flow channel.
- the first sample quantification chamber 9 and the second sample quantification chamber 10 are provided to achieve better separation of upper plasma and lower blood cells and quantification of plasma samples.
- the diluent quantitative chamber 15 is communicated with the diluent storage chamber 12.
- the diluent quantitative chamber 15 needs to be farther from the center of the chip body 3 than the diluent storage chamber 12. Therefore, when the chip body 3 is rotated by the centrifugal device, the diluent storage The diluent in the cavity 12 will flow toward the diluent dosing cavity 15 due to centrifugal action.
- the volume ratio of the first sample quantitative chamber 9 and the second sample quantitative chamber 10 to the diluent quantitative chamber 15 determines the mixing ratio of the reaction sample and the diluent.
- the overflow chamber includes a sample overflow chamber 11 and a diluent overflow chamber 16, which are respectively connected with the first sample quantitative chamber 9 and the diluent quantitative chamber 15.
- the sample overflow chamber 11 is farther from the center of the chip body 3 than the first sample quantitative chamber 9 and the second sample quantitative chamber 10 . Therefore, when the chip body 3 is rotated by centrifugal driving, there are more samples than the first sample quantitative chamber 9 .
- the sample with the capacity of the second sample quantitative chamber 10 will flow into the sample overflow chamber 11 due to the centrifugal force.
- the diluent overflow chamber 16 is farther from the center of the chip body 3 than the diluent quantitative chamber 15. Therefore, when the chip body 3 is rotated by centrifugal driving, the diluent that is larger than the diluent quantitative chamber 15 will be driven by centrifugal force. Flow to the diluent overflow chamber 16.
- the microfluidic channel between the first sample quantitative chamber 9 and the sample overflow chamber 11 is also connected to the outside of the chip via a sample ventilation channel 23 .
- the microchannel between the diluent quantitative chamber 15 and the diluent overflow chamber 16 The flow channel is also connected to the outside of the chip via a diluent vent channel 24 . Vented channels are provided for smoother flow of diluents and samples.
- the quantitative mixing chamber 17 communicates with the first sample quantitative chamber 9 and the second sample quantitative chamber 10 respectively through the microchannel I191, and communicates with the diluent quantitative chamber 15 through the microchannel II192.
- the quantitative mixing chamber 17 needs to be relatively
- the first sample quantification chamber 9, the second sample quantification chamber 10, and the diluent quantification chamber 15 are far from the center of the chip body 3, and the quantitative sample and the quantitative diluent can be mixed and diluted for detection.
- the quantitative mixing chamber 17 makes the mixed liquid flow into each reaction chamber 18 in the reaction chamber through the microfluidic channel III 193 and the microfluidic channel IV194 so as to react with the detection reagent therein.
- the reaction chamber includes several equidistantly distributed reaction chambers 18 and a sample blank chamber 21 at the end of the flow channel.
- the volume of the reaction chambers 18 is the same, and the reaction reagents required for the reaction are contained therein.
- the reaction reagents can be frozen.
- the lyophilized beads produced by the dry method the radius of each lyophilized bead is between 0.5mm and 1mm, and the small volume of the reaction reagent increases the carrying capacity of the reaction chamber 18 in the same size chip, effectively improving the Detection sensitivity and detection efficiency, in addition, the use of lyophilized beads for the reaction reagents effectively increases the shelf life of the reagents in storage.
- the channel of the sample blank chamber 21 is wider than the channels of the other reaction chambers 18 , thereby providing more storage space for the overflow of the chip mixing liquid.
- the sample blank chamber 21 can allow the liquid in the quantitative mixing chamber 17 to enter, to eliminate the influence of different samples on the detection results and to detect whether the amount of reaction sample and diluent entering the reaction chamber 18 is sufficient, so that the detection results are more accurate.
- the sample blank chamber 21 in the multifunctional microfluidic chip of the present invention can also be used as a mixed liquid overflow chamber. After each reaction chamber 18 has reacted, the excess mixed liquid can enter the sample blank chamber 21 .
- the quantitative mixing chamber 17 and the sample blank chamber 21 are respectively communicated with the ventilation holes I 221 and the ventilation holes II 222 through the micro flow channel.
- the ventilation hole I221 and the ventilation hole II222 run through the chip body 3 located in the lower layer of the chip.
- the ventilation hole I221 and the ventilation hole II222, the ventilation hole I221 and the ventilation hole can be seen on the back of the chip body 3 The setting of II222 makes the liquid flow more smoothly.
- the diluent stored in the aforementioned diluent storage chamber 12 is encapsulated in the diluent sac 13 in a liquid state, and the bottom surface of the diluent sac 13 is provided with a sealing film, which is made of a pierceable material, such as plastic, aluminum foil or aluminum-plastic composite material, etc.
- the supporting detection instrument squeezes the diluent capsule 13 through the upper diluent storage chamber through hole 262 of the upper layer 1 of the chip, so that the sealing film on the bottom surface of the diluent capsule 13 is in contact with the puncturing structure 14, so that the diluent capsule 13 is ruptured. Internal diluent flows out.
- the pipe shape design of the aforementioned microchannel I191, microchannel II192 and microchannel III193 is based on the capillary action and siphon effect, and is set according to the experimental requirements.
- the inflection point of the microchannel I191 is closer to the chip body than the sample quantitative cavity. 3; the inflection point of the microchannel II 192 is closer to the center of the chip body 3 than the dilution quantitative chamber 15; the inflection point of the microchannel III 193 is closer to the center of the chip body 3 than the quantitative mixing chamber 17;
- the capillary action makes the liquid flow to the inflection point of the microchannel; then centrifugal force is applied, and the liquid flows into the next chamber under the siphon action, acting as a siphon valve.
- the multifunctional microfluidic chip of the present invention also includes a set of positioning holes 25 located on the left and right sides of the quantitative mixing chamber 17, which are specifically used to ensure the positional accuracy between the chip layers, and the positioning holes pass between the chip layers. 25 are plugged into one.
- the multifunctional microfluidic chip of the present invention also includes splicing card positions 20 located on the left and right sides of the upper edge of the chip body 3, which are specifically used for splicing two adjacent chips; and finally three The sector-shaped chip body 3 can be spliced into a circular chip to further increase the number of samples to be tested.
- the specific process is as follows: the whole blood sample enters the sampling cavity 4 through the upper sampling cavity through hole 261, and is put into the matching detection instrument, and the diluent of the detection instrument releases the upper diluent of the structure.
- the storage cavity through hole 262 squeezes the diluent bag 13, so that the sealing film on the bottom surface of the diluent bag 13 contacts the puncturing structure 14, so that the diluent bag 13 is ruptured and the diluent flows out.
- the blood and the diluent flow through different microchannel paths respectively, the blood sample enters the first sample quantitative chamber 9 and the second sample quantitative chamber 10, and the excess blood enters the sample overflow chamber 11 through the microchannel , the blood sample is centrifuged into an upper layer of plasma and a lower layer of blood cells, and the lower layer of blood cells is mainly deposited in the first sample quantification chamber 9; the diluent enters the diluent quantification chamber 15 through the microchannel, and the excess dilution in the diluent quantification chamber 15
- the liquid enters the diluent overflow chamber 16 through the microfluidic channel; the setting of the ventilation channel makes the flow of the diluent and the blood sample smoother, and the centrifugal action can be set to different rotational speeds and centrifugation directions; after the centrifugation is stopped, the plasma and the diluent are under the capillary action.
- the excess mixing liquid enters the sample blank chamber 21, the three-dimensional size and volume of the reaction chamber 18 and the sample blank chamber 21 are the same, the fixed reagent formulations inside the reaction chamber 18 are different, and the sample blank chamber 21 also serves as a mixing liquid overflow Flow chamber, ventilation holes I 221 and ventilation holes II 222 are arranged to make the liquid flow smoothly; the mixed liquid dissolves the preset immobilized reaction reagent (lyophilized beads) in the reaction chamber 18, fully reacts, and is equipped with the optical path detection device of the detection instrument Optical detection is performed on each reaction chamber, and the detection results are calculated.
- the ratio of the reaction sample to the diluent in the present invention is fixed, and the ratio is designed to be less than 1:30, such as 1:40, 1:50, etc., which are designed according to actual application needs; after the ratio of the reaction sample to the diluent is determined, the design structure is fixed.
- the microfluidic chip can realize the simultaneous detection of multiple indicators only by changing the detection reagent formula in the reaction chamber 18, and the blood collection volume is small, and only 20 ⁇ L (one drop of blood) is required for one injection, and multiple indicators can be achieved.
- the blood sample consumption is only one-tenth to one-fifth of the ordinary products on the market, so it is especially suitable for clinical testing of neonatal and long-term tumor patients who have difficulty in blood collection due to radiotherapy, chemotherapy and other reasons.
- the difference between the solution in the sample blank chamber 21 in the reaction chamber and the solution in the reaction chamber 18 is that it does not contain a reaction reagent, that is, the mixed solution after mixing the reaction sample and the diluent is used as the sample blank. This method can The reliability of the detection results is greatly improved.
- the multifunctional microfluidic detection chip of the present invention can be used for detection items including biochemical items, immune items, nucleic acid molecule items and blood coagulation items.
- biochemical indicators include total bilirubin, direct bilirubin, total bile acids, total protein, albumin, albumin/globulin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, ⁇ -glutamyl transaminase Peptidase, potassium, sodium, chloride, calcium, magnesium, phosphorus, iron, carbon dioxide, ammonia, aspartate aminotransferase mitochondrial isoenzyme (ASTm), lactate dehydrogenase (LDH), creatine kinase (CK) , ⁇ -hydroxybutyrate dehydrogenase ( ⁇ -HBD), creatine kinase isoenzyme (CK-MB), urea nitrogen (BUN), creatinine (Cr), cysteinase inhibitor
- Immune items include cardiac troponin I, procalcitonin, N-terminal brain natriuretic peptide precursor, thyroid stimulating hormone, total triiodothyronine, free triiodothyronine, total thyroxine, free thyroxine , estradiol, anti-Mullerian hormone, brain natriuretic peptide, cardiac fatty acid-binding protein, interleukin-6, lipoprotein-associated phospholipase A2, serum amyloid A, soluble growth-stimulating gene 2 protein, creatine kinase CK-MB, myoglobin Myo, luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone, progesterone, 25-hydroxyvitamin D3, 25-hydroxyvitamin D, immunoglobulin G4, cardiac troponin T , myeloperoxidase, aldosterone, renin, homocysteine, D-dimer, S100-bet
- Nucleic acid molecule project indicators include Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila, Influenza A virus, Influenza B virus, Bacillus pertussis, Streptococcus pneumoniae, Respiratory syncytial virus, Parainfluenza virus, Rhinovirus, Respiratory adenovirus.
- Blood coagulation items include prothrombin time PT, thrombin time TT, activated partial thromboplastin time APTT, activated coagulation time ACT, fibrinogen FIB, fibrin degradation product FDP, coagulation factor Xa, viper venom time (RVVT) , Antithrombin III (AT III), D-dimer (D-Dimer).
- the detection reagent is fixed in the reaction chamber 18, and the freeze-drying method is used, that is, freeze-dried beads are made, and each freeze-dried bead has a diameter of 0.5-1.0 mm and a diameter of 4-8 mm.
- the freeze-drying method is used, that is, freeze-dried beads are made, and each freeze-dried bead has a diameter of 0.5-1.0 mm and a diameter of 4-8 mm.
- Frozen bead preparation adjust the drop volume of the automatic bead drop machine (Xiamen Wumen Automation Technology Co., Ltd.; LC200-R) to be accurate to 2-100 microliters (preferably 4 microliters) for each drop of reagent beads, and put it into the matching container.
- the reagents are dropped into the liquid nitrogen to quickly form frozen beads and sink to the bottom of the liquid nitrogen container. Finally, the frozen beads are poured into the freeze-drying container for further vacuum. Freeze-dried.
- Preparation of freeze-dried beads put the above-mentioned frozen beads into a vacuum freeze-drying apparatus (Shanghai Tofflon Technology; LYO-0.5), set the instrument parameters, and the drying time is 24-28 hours, and the frozen beads are dehydrated to form freeze-dried beads. Take it out into an airtight container.
- a vacuum freeze-drying apparatus Shanghai Tofflon Technology; LYO-0.5
- the microfluidic detection chip of the present invention has a fixed structure, and the ratio of the reaction sample to the diluent is designed to be 1:50.
- the diluent flows out from the diluent storage chamber 12 and enters the diluent quantitative chamber 15, and the excess diluent enters the diluent
- the whole blood sample is centrifuged into layers, and blood cells are mainly deposited in the first sample quantitative chamber 9, and the second sample quantitative chamber 10 is plasma.
- the quantitative plasma 4 ⁇ L and the quantitative diluent 200 ⁇ L are quantitatively mixed.
- reaction chamber 17 After mixing in the chamber 17, it enters nine reaction chambers 18 and one sample blank chamber 21 with the same capacity.
- the mixed solution dissolves the fixed reaction reagent in the reaction chamber 18 and reacts fully.
- the optical path detection device of the matching detection instrument is suitable for Each reaction chamber 18 and the sample blank chamber 21 are optically detected to obtain a detection result.
- the detection results of the 9 reaction chambers 18 are subtracted from the detection results of the sample blank chamber 21, which eliminates the influence of different samples on the results, and can also detect whether the amount of reaction samples and diluents entering the reaction chamber 18 is sufficient, which both improves The dual function of the accuracy of the test results and the judgment of the validity of the test.
- the blood sample consumption of the present invention is only 1/10-1/5 of that of common products on the market, and the blood collection volume is small, and is especially suitable for clinical detection of neonatal and long-term tumor patients with difficulty in blood collection due to radiotherapy, chemotherapy and other reasons.
- the structure of the microfluidic detection chip is fixed, and the ratio of reaction sample and diluent is fixed. Only by changing the reagent formula required for different detection indicators, a chip design template can be realized to meet the clinical detection of different projects or project combinations.
- the setting of the splicing card position 20 can assemble three chip detection chips into one circular detection chip, and can detect three different samples at the same time, thereby increasing the throughput of the detection samples.
- the volume ratio of the sample of the present invention to the detection reagent is as follows compared with the market product 1 and product 2:
- the sample-to-reagent ratio of product 1 and product 2 is not fixed, but the present invention uses the chip as a carrier to achieve the fixed ratio of sample to reagent, and then the structure of the chip is fixed, and the three-dimensional size and volume of the reaction pool are the same, ensuring that the reaction pool enters the reaction pool.
- the sample volume is the same, just change the reagent formula of different detection indicators, the chip structure is fixed, the cost of mold opening is reduced, and it is conducive to mass production.
- the present invention detects 9 indicators, and roughly calculates the blood volume of each indicator to be 2.2 ⁇ L. Only 1 drop of blood can actually be used to detect 9 indicators, and the blood collection volume is small, especially suitable for the clinical detection of neonatal and long-term tumor patients who have difficulty in blood collection due to radiotherapy, chemotherapy and other reasons.
- the product of the present invention can achieve better performance, and the product testing result is accurate and stable.
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Abstract
Description
产品 | 产品3 | 本发明 |
进血样量 | ≥120.0μL | 20μL |
检测指标个数 | ≤16 | 9 |
用血量/指标 | ≥7.5μL | 2.2μL |
Claims (13)
- 一种多功能微流控检测芯片,其特征在于:所述芯片包括芯片本体,芯片本体上设置有进样腔、样本定量腔、样本溢流腔、稀释液存储腔、稀释液定量腔、稀释液溢流腔、定量混匀腔、反应腔以及透气孔;所述进样腔可供注入待检测的反应样本,通过微流道与所述样本定量腔相连,反应样本能从所述进样腔进入所述样本定量腔,多余的反应样本进入所述样本溢流腔;所述稀释液存储腔通过微流道与所述稀释液定量腔相连,稀释液能从所述稀释液存储腔进入所述稀释液定量腔,多余的稀释液进入所述稀释液溢流腔;所述反应腔包括一个或多个反应腔室以及一个样本空白室;所述样本定量腔的反应样本和所述稀释液定量腔的稀释液在所述定量混匀腔混匀之后,混匀液通过微流道进入反应腔室与其中的反应试剂进行反应以待检测,同时混匀液进入样本空白室作为样本空白待检测,所述反应腔室与所述样本空白室三维大小相同;所述样本空白室的通道比反应腔室的通道宽;所述定量混匀腔中反应样本与稀释液的定量比小于1:30。
- 根据权利要求1所述的多功能微流控检测芯片,其特征在于:所述样本定量腔包括第一样本定量腔和第二样本定量腔。
- 根据权利要求1所述的多功能微流控检测芯片,其特征在于:所述反应腔包括若干个等距分布的反应腔室。
- 根据权利要求1所述的多功能微流控检测芯片,其特征在于:所述样本定量腔的反应样本和所述稀释液定量腔的稀释液分别经微流道Ⅰ、微流道Ⅱ进入所述定量混匀腔混匀之后;所述混匀液依次经微流道Ⅲ、微流道Ⅳ进入所述反应腔室和所述样本空白室;所述微流道Ⅰ、微流道Ⅱ和微流道Ⅲ分别包括一相对于相应液体流出腔室靠近所述芯片本体中心位置的拐点。
- 根据权利要求1所述的多功能微流控检测芯片,其特征在于:所述定量混匀腔和所述反应腔分别与透气孔连通。
- 根据权利要求1所述的多功能微流控检测芯片,其特征在于:所述定量混匀腔中反应样本与稀释液的定量比为1:50。
- 根据权利要求1所述的多功能微流控检测芯片,其特征在于:所述反应试剂为采用冻干法制作的冻干珠。
- 根据权利要求7所述的多功能微流控检测芯片,其特征在于:所述冻干珠的半径介于0.5mm到1mm。
- 根据权利要求1所述的多功能微流控检测芯片,其特征在于:所述样本定量腔和样本溢流腔之间的微流道还设有一个样本透气通道连接到芯片外部,所述稀释液定量腔和所述稀释液溢流腔之间的微流道也设有一个稀释液透气通道连接到芯片外部。
- 根据权利要求1所述的多功能微流控检测芯片,其特征在于:所述芯片为扇形结构。
- 根据权利要求1所述的多功能微流控检测芯片,其特征在于:所述芯片还包括芯片上层和芯片中层,所述芯片本体位于下层。
- 根据权利要求1所述的多功能微流控检测芯片,其特征在于:所述芯片本体两侧各设有一个拼接卡位。
- 根据权利要求1所述的多功能微流控检测芯片,其特征在于:所述芯片本体可用于检测生化项目、免疫项目、核酸分子项目以及血凝项目。
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CN115193358A (zh) * | 2022-07-21 | 2022-10-18 | 扬州大学 | 一种试管形多功能微流控反应装置 |
CN115193358B (zh) * | 2022-07-21 | 2024-05-28 | 扬州大学 | 一种试管形多功能微流控反应装置 |
CN115055287A (zh) * | 2022-08-12 | 2022-09-16 | 普迈德(北京)科技有限公司 | 一种离心式微流控芯片、送盘装置以及血浆分离取样方法 |
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US20230249180A1 (en) | 2023-08-10 |
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