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CN205449989U - Biochip - Google Patents

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Publication number
CN205449989U
CN205449989U CN201490000637.4U CN201490000637U CN205449989U CN 205449989 U CN205449989 U CN 205449989U CN 201490000637 U CN201490000637 U CN 201490000637U CN 205449989 U CN205449989 U CN 205449989U
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China
Prior art keywords
biochip
substrate
reaction
detector unit
detection
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Expired - Fee Related
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CN201490000637.4U
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Chinese (zh)
Inventor
董建国
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SHANGHAI PAILAIXING BIOTECHNOLOGY Co Ltd
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SHANGHAI PAILAIXING BIOTECHNOLOGY Co Ltd
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00Instruments for taking body samples for diagnostic purposes; Other methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determination; Throat striking implements
    • A61B10/0045Devices for taking samples of body liquids
    • A61B2010/0074Vaginal or cervical secretions

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Immunology (AREA)
  • Urology & Nephrology (AREA)
  • Cell Biology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

The utility model discloses a biochip, including base plate and film, be equipped with detecting element on the base plate, the detecting element surface that the film covered at this base plate. The utility model also discloses an application of above -mentioned biochip in the product of the clinical liquid sample of preparation detection. The utility model discloses a biochip, can the clinical liquid sample median microorganism of direct detection the situation of change of register for easy reference or biochemical material, quick, simple and convenient, the objectivity is strong, the degree of accuracy is high, application prospect is very wide.

Description

Biochip
Technical field
The present invention relates to clinical diagnosis technical field of medical instruments, particularly relate to a kind of biochip and application thereof.
Background technology
At present, detect vaginal secretions, mouth mucus, gastro-intestinal secretion thing, the blood of extraction, body fluid, ascites pleural fluid or urine etc. clinically, generally it is required for first gathering the clinical fluid samples such as vaginal secretions, mouth mucus or gastro-intestinal secretion thing, then sample is taken laboratory tests operation.During inspection, typically first the clinical sample of collection is carried out eluting dilution, then it is added drop-wise in reaction utensil or test strips through processes such as colour developings, pH value measures and requires that directly the colour developing of contact secretions is observed, and other reaction dilutes through eluting, can not unified operation, detect more indirect after dilution simultaneously, also sensitivity can be reduced, operating procedure is many, poor accuracy, for bedside doctor, there are multiple operating procedure and judge index, the most time-consuming and loaded down with trivial details, for laboratory, it is transplanted on laboratory and carries out experimental implementation, middle transfer handover time is longer, the materials such as enzyme are easily degraded and changes, affect verity and the accuracy of result.
As a example by detecting with the bacterial vaginosis (bacterialvaginosis, BV) of gynecological.Bacterial vaginosis is one of the women of child-bearing age's modal vaginal infection disease, and infection rate is at 30-50%, and sickness rate is at 10-20%, and number of patients is significantly larger than the number of the infected of trichomonas vaginitis, mycete etc., and easily recurs.It addition, the Patients with Bacterial Vaginosis of about 50% because being affected adversely diagnosis and treatment without obvious clinical symptoms.At present, Amsel standard and Nugent standard are the what is called " goldstandard " of the big diagnosing bacterial vagina disease of two generally acknowledged in the world.Amsel standard is to have three in following four indices to be i.e. diagnosed as bacterial vaginosis simultaneously: (1) vagina has secretions homogeneous, thin, white;(2) vaginal pH > 4.5;(3) amine test is positive;(4) clues cell is positive.Nugent standard is by different shape classification of flora and integration in vaginal secretions are diagnosed BV.
In clinical practice, Amsel standard has the disadvantage that 1.pH pH-value determination pH is inconvenient, and 2. vaginal secretions character judges that subjectivity is strong, and 3. olfactory test staff compliance and objectivity are poor, and 4. clues cell is circumstantial evidence;Nugent standard there is also needs smear, Gram’s staining, then under oil mirror, the kind of single antibacterial is differentiated, is counted and integration, and professional experiences is strong, loaded down with trivial details, time-consuming.
Along with deepen continuously understanding pathogenetic to BV, create the diagnostic method based on the metabolite of microorganism specific to detecting in BV patient's vaginal secretions and occur in that some commercial reagents boxes, " the gynaecologic multi-item dry chemical united detection test paper bar " of such as China Intellectual Property Office's Publication No. CN201247244 and " a kind of bacterial vaginosis device for fast detecting of Publication No. CN101975852A, test strip and detection method ", these methods are objective compared with said method and are suitable to batch operation, but also need specimen is taken laboratory inspection operation, color changes to want naked eyes to judge, it is required for gathering vaginal secretions by swab, eluting dilutes, then the process such as colour developing in reaction utensil or test strips it is added drop-wise to.Operating procedure is many, poor accuracy, the most time-consuming and loaded down with trivial details.
Therefore it is badly in need of a kind of energy at present and detects the medical device of clinical fluid specimen fast, accurate and comprehensively.
Summary of the invention
The invention solves the problems that at present detection clinical fluid specimen is time-consuming, loaded down with trivial details, the technical problem of poor accuracy, a kind of biochip is provided, this biochip can directly detect microorganism spectrum or the situation of change of biochemical substances in clinical fluid sample, quickly, easy, objectivity is strong, accuracy is high, eliminate collection, eluting, dilute, the shortcoming of the multi-step such as dropping operation, result can be directly obtained at bedside.
In addition, it is also desirable to provide the application of a kind of above-mentioned biochip.
In order to solve above-mentioned technical problem, the present invention is achieved through the following technical solutions:
In one aspect of the invention, it is provided that a kind of biochip, including substrate and thin film, described substrate is provided with detector unit, and described thin film covers on the detector unit surface of this substrate.
Described detector unit can be by the surface adsorption of substrate or the reaction speckle that formed through being dried after combining different reaction reagents.
Described detector unit can also be integrally fixed at the detection buttress of substrate surface, and this detection buttress is that after being adsorbed by reaction carriers or combining differential responses reagent, warp is dried and is formed.
Described detector unit can also be that this membranaceous reaction carriers is placed on described substrate by the reaction speckle being positioned on this membranaceous reaction carriers formed through being dried after adsorbing on membranaceous reaction carriers or combining different reaction reagents.
Described detector unit can also is that the reaction wells being located on substrate, and this reaction wells inner bottom part adsorbs or is combined with differential responses reagent drying.
Preferably, described thin film is the semipermeable membrane with micropore, it is possible to allows testing liquid quickly enter with reagent and contacts and react, and can prevent testing liquid reflux from reagent can be prevented again to be exuded to outside thin film simultaneously.
Preferably, described substrate is optical clear material.
Preferably, described biochip is provided with bar code or Quick Response Code.
In another aspect of this invention, additionally provide the application of a kind of biochip, for preparing the product of detection clinical fluid sample.
Described clinical fluid sample includes vaginal secretions, mouth mucus, gastro-intestinal secretion thing, blood, body fluid, ascites pleural fluid or urine.
The biochip of the present invention, can directly detect microorganism spectrum or the situation of change of biochemical substances in clinical fluid specimen, eliminate collection clinical fluid specimen and transfer clinical laboratory, eluting dilutes, then eluent being added drop-wise to reacts on reagent paper or these operating procedures that develop the color in the reacting hole of Sptting plate, quickly, convenient, directly, objectivity is strong, with the use of photoelectricity reading apparatus, biochip from check point or can be directly placed into photoelectricity reading apparatus after taking out from fluid to be measured and obtains testing result by tester, it is suitable for the operation of hospital outpatient doctor's bedside or patient home uses, it is laboratory medicine just-in-time and bedside (pointofcaretesting, POCT) embodiment.
Accompanying drawing explanation
The present invention is further detailed explanation with detailed description of the invention below in conjunction with the accompanying drawings.
Fig. 1 to Fig. 4 is the structural representation of biochip of the present invention.
Wherein: 100, biochip;110, substrate;120, thin film;130, detector unit;140, reaction carriers;150, membranaceous reaction carriers;151, the detector unit on membranaceous reaction carriers;160, reaction wells;111, substrate two sides medial recess.
Detailed description of the invention
As shown in Figure 1, the biochip 100 of the present invention, including substrate 110 and thin film 120, wherein, substrate 110 is square or rectangle, it is also possible to be circular or oval, area is 1 to 800 square millimeter, thickness is 0.5 to 10 millimeter, and long-pending after optimization is 30 to 300 square millimeters, and thickness is 1 to 3 millimeter;nullSubstrate 110 is colourless optically transparent,Preferably,A depression 111 is had in the middle part of the two sides of substrate 110,A knife-edge draw-in groove it is respectively arranged with in the middle part of front the 1/3 of substrate 110 two sides,One face of this substrate processes through surface can be with physical absorption or chemical bond particular detection reagent drying,Form different detector units 130,These reagent of detector unit 130 can be various reaction molecular such as antigen、Antibody、DNA、RNA、Enzyme、Zymolyte、Biochemical reagents or its mixture,Can react with the specific molecular at detection position,Different reagent set is as different detector unit absorption or is combined on that face surface treated of substrate 110,Form the reaction speckle of array arrangement,Thin film 120 is covered the most again at the real estate responding speckle,This thin film 120 has micropore,Liquid and biomacromolecule can pass through,This thin film is preferably provided with unidirectional fluidity,Liquid can be allowed to quickly enter with reagent and to contact and react,Can prevent liquid reflux from reagent can be prevented again to be exuded to outside thin film.
As biochip of the present invention another kind of embodiment mode as shown in Figure 2, detectable is adsorbed or is combined on reaction carriers 140, drying forms detector unit, different detector units is fixed on substrate 110, form the detection buttress of array arrangement, cover thin film 120 in substrate 110 face having detection buttress the most again;Reaction carriers 140 can use macromolecular material such as pellets of synthetic resins, silica gel particle or natural fiber such as filter paper, paper fiber or inorganic material such as alumina particle, nanogold particle, gold and metal-oxide composite particles;The meshed material of various organic or inorganic can also be used.
As biochip of the present invention another kind of embodiment mode as shown in Figure 3, detectable is adsorbed or is combined on membranaceous reaction carriers 150, drying forms detector unit 151, different detector units 151 array on membranaceous reaction carriers is arranged into reaction speckle, reaction carriers 150 is presented herein below substrate 110, and reaction carriers 150 covers thin film 120 above;Membranaceous reaction carriers 150 can use macromolecular material such as nitrocellulose filter, non-woven fabrics or natural fiber material such as filter paper or inorganic fibers such as glass fibre etc..
As biochip of the present invention another kind of embodiment mode as shown in Figure 4, respond trap 160 on substrate 110 to arrange in array-like, substrate 110 is colourless optically transparent, the degree of depth of reaction wells 160 is 0.1 to 10 millimeter, optimize is 0.5 to 3 millimeter, the number of reaction wells 160 by the index needing detection how many depending on, reaction wells 160 can be any shape;The bottom surface of reaction wells 160 is as the detecting window of detection color reaction;There is absorption in reaction wells 160 or combine the reaction carriers of detectable drying; this reaction carriers can use macromolecular material such as pellets of synthetic resins, silica gel particle etc.; or natural fiber such as filter paper, cellulose, or inorganic microparticle or fibrous material such as alumina particle, nanogold particle, gold and metal-oxide composite particles, glass fibre etc.;The meshed material of various organic or inorganic can also be used;The manufacturing process of this reaction carriers is that cellulose, super absorbent resin, reagent are mixed to form detection slurry, the most again this detection slurry is injected described reaction wells, dried.Substrate 110 covers thin film 120 above, covers reaction wells mouth simultaneously.
As the improvement of the present invention, reaction carriers 140 is multiple-layer stacked, and every layer is impregnated with different reaction reagents respectively.
As the improvement of the present invention, reaction carriers 150 is multiple-layer stacked, and every layer is impregnated with different reaction reagents respectively.
As the improvement of the present invention, reaction wells 160 bottom surface can directly be adsorbed through chemically or physically processing or be responded reagent drying by chemical bonds.
As the improvement of the present invention, on substrate 110, reaction tank bottom has optical fiber, is used for detecting the color change of detector unit.
As the improvement of the present invention, biochip has bar code or Quick Response Code.
Another kind of embodiment mode as the present invention is that described covering can replace by filtration membrane bag at the thin film of substrate surface, i.e. substrate and reaction member is wrapped up by filtration membrane bag, after take out the filtration membrane bag being surrounded by biochip from detection position, filtration membrane bag is divested.
The operation principle of biochip of the present invention is the characteristic or the characteristic of luminescence that color can be occurred to change based on reaction system after some specific enzymatic reaction, immunoreation or chemical reaction, certain specific tested molecule of perception or ion exist or the change of amount, the number of its amount is relevant to the brightness of the depth of color or light, and this molecule or ion may represent body certain damage, unbalance, the existence of certain antibacterial of metabolism or change of amount, or the change of the acid-base value of reflection environment;Generally well-known technical method has dry chemical method, euzymelinked immunosorbent assay (ELISA), gold colloidal, immunoluminescence method, electrochemiluminescence, fluorescent marker method etc., so-called dry chemical method be apply some biochemical reaction or enzymatic chemical reaction after there is color change and judge tested molecule whether exist and measure number principle, reagent-impregnated required for reaction is adsorbed or is connected in drying process on filter paper, during detection, sample is added on filter paper observation color change.Such as intravaginal is inflamed when reacting, assemble in intravaginal due to the chemotaxis of polymorphonuclear leukocyte and discharge leukocyte esterase in a large number, the activity of the esterase of polymorphonuclear leukocyte release is detected under this inflammatory conditions, vaginal secretions cleannes, the degree of vaginal mucosa damage can be reacted, be that auxiliary diagnoses a colpitic important indicator;The bromo-4-of 5-chloro-3-indolyl acetic acid salt is hydrolyzed according to leukocyte esterase, discharge bromo indole base, the latter is in the presence of oxygen in blueness, the chemical reaction character being directly proportional to leukocyte esterase activity in color depth, the reaction carriers bromo-4-of such as filter paper impregnation substrate 5-chloro-3-indolyl acetic acid salt drying is processed, above-mentioned chemical reaction can occur when running into vaginal secretion, be appreciated that the activity of leukocyte esterase by measuring blue weight and then judge that vaginal secretions cleannes, vaginal mucosa are damaged or the degree of inflammation.Equally, by the detection information such as lactic acid, oxidase, infusorian specific for hydrolysis albumen, pH value, concentration of hydrogen peroxide, neuraminidase activity, Prolyl iminopeptidase activity, amino glucosaccharase activity, polyamines, nitrite, heme come which antibacterial of comprehensive descision intravaginal be dominant microflora, with or without flora unbalance, acid-base value just, with or without Tiny ecosystem situations such as infusorian, mycete or coli-infections.Testing index like this can be made different types of detector unit according to testing goal difference and be integrated on one piece of substrate and make biochip by the present invention, during detection, biochip is pasted on the vaginal wall, vaginal secretion penetrates into biochip, directly gather the multiple Pathological Information of checked object, then biochip is put into photoelectricity reading apparatus, assists diagnosis vagina by reading and comprehensively analyze biochip information.
The present invention can change the reaction carriers of the biochemical reagents on reaction carriers and varying number and kind according to different diagnosis objects, therefore the biochip of the present invention can be not only used for vaginal microenvironment detection, it may also be used for oral cavity, gastrointestinal tract, the blood of extraction, body fluid, ascites pleural fluid, urine or the diluent etc. of these liquid.
Embodiment 1
As it is shown in figure 1, biochip 100 of the present invention is made up of substrate 110 and thin film 120, substrate 110 area is approximately 80 square millimeters, and thickness is approximately 1 millimeter, and substrate 110 colourless optical clear poly-H methyl methacrylate H (PMMA) is made;110 1 faces of substrate are after surface processes and processes such as chromium gelatin, by physical absorption or chemical bond particular detection reagent drying, form the different detector units 130 such as detection pH value, hydrogen peroxide, leukocyte esterase, neuraminidase, Prolyl iminopeptidase, acetyl glucosaminidase, each detector unit 130 includes a detection membrane block and a blank film block, each film block length is wide is respectively approximately 1.2 millimeters, array arrangement with 3 × 4 is on substrate, cover the hydrophilic non-woven with micropore again above, fix with substrate pressing.A depression 111 is had in the middle part of the two sides of substrate.
Embodiment 2
As shown in Figure 2, biochip 100 of the present invention is made up of substrate 110, the reaction carriers 140 of immersion detection reagent and thin film 120, substrate 110 area is approximately 130 square millimeters, and thickness is approximately 2 millimeters, and substrate 110 colourless optical clear poly-H methyl methacrylate H (PMMA) is made;One plate face of substrate 110 processes through chromium gelatin;It is respectively prepared pH value, hydrogen peroxide, leukocyte esterase, neuraminidase, Prolyl iminopeptidase, acetyl glucosaminidase detector unit as reaction carriers impregnated agent with pellets of synthetic resins, each detector unit includes a detection membrane block and a blank film block, each film block length is wide is respectively approximately 1.5 millimeters, array arrangement with 3 × 4 is on substrate, cover the hydrophilic non-woven with micropore again above, fix with substrate pressing.A depression 111 is had in the middle part of the two sides of substrate.
Embodiment 3
As shown in Figure 3, biochip 100 of the present invention is made up of substrate 110, the reaction carriers 150 of immersion detection reagent and thin film 120, substrate 110 area is approximately 144 square millimeters, and thickness is approximately 2 millimeters, and substrate 110 colourless optical clear poly-H methyl methacrylate H (PMMA) is made;One plate face of substrate 110 processes through chromium gelatin;It is respectively prepared pH value, hydrogen peroxide, leukocyte esterase, neuraminidase, Prolyl iminopeptidase, acetyl glucosaminidase detector unit as reaction carriers impregnated agent with filter paper, each detector unit includes a detection membrane block and a blank film block, each film block length is wide is respectively approximately 1.8 millimeters, array arrangement with 3 × 4 is on substrate, cover the hydrophilic non-woven with micropore again above, fix with substrate pressing.A depression 111 is had in the middle part of the two sides of substrate.
Embodiment 4
As shown in Figure 4, biochip 100 of the present invention is made up of substrate 110, reaction carriers and thin film 120, and substrate 110 area is about 192 square millimeters, and thickness is approximately 2 millimeters, and substrate 110 is made with colourless optical clear polydimethylsiloxane (PDMS);The arrangement of trap 160 array-like is responded on substrate 110;The length and width of each reaction wells 160 are respectively approximately 1.5 millimeters, and the degree of depth is approximately 1 millimeter, and the array arrangement with 4 × 6 is on substrate;Paper pulp, super absorbent resin (SAP), reagent mixing are respectively prepared pH value, hydrogen peroxide, leukocyte esterase, neuraminidase, Prolyl iminopeptidase, acetyl glucosaminidase, nitrite, oxidase, infusorian specific for hydrolysis albumen, amino glucosaccharase activity, polyamines, heme detection slurry, it is then injected in reaction wells 160, dried;It is coated with the hydrophilic non-woven of micropore again above, fixes with substrate pressing.A depression 111 is had in the middle part of the two sides of described substrate.
Embodiment described above only have expressed embodiments of the present invention, and it describes more concrete and detailed, but therefore can not be interpreted as the restriction to the scope of the claims of the present invention.It should be pointed out that, for the person of ordinary skill of the art, without departing from the inventive concept of the premise, it is also possible to make some deformation and improvement, these broadly fall into protection scope of the present invention.Therefore, the protection domain of patent of the present invention should be as the criterion with claims.

Claims (8)

1. a biochip, it is characterised in that including that substrate and thin film, described substrate are provided with detector unit, described thin film covers on the detector unit surface of this substrate.
Biochip the most according to claim 1, it is characterised in that described thin film is the semipermeable membrane with micropore.
Biochip the most according to claim 1, it is characterised in that described detector unit is by the surface adsorption of substrate or the reaction speckle that formed through being dried after combining different reaction reagents.
Biochip the most according to claim 1, it is characterised in that described detector unit is integrally fixed at the detection buttress of substrate surface, this detection buttress is that after being adsorbed by reaction carriers or combining differential responses reagent, warp is dried and is formed.
Biochip the most according to claim 1, it is characterized in that, described detector unit is that this membranaceous reaction carriers is placed on described substrate by the reaction speckle being positioned on this membranaceous reaction carriers formed through being dried after adsorbing on membranaceous reaction carriers or combining different reaction reagents.
Biochip the most according to claim 1, it is characterised in that described detector unit is provided at the reaction wells on substrate, this reaction wells inner bottom part adsorbs or is combined with differential responses reagent drying.
Biochip the most according to any one of claim 1 to 6, it is characterised in that described substrate is optical clear material.
Biochip the most according to claim 7, it is characterised in that described biochip is provided with bar code or Quick Response Code.
CN201490000637.4U 2013-05-09 2014-01-08 Biochip Expired - Fee Related CN205449989U (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN2013101705804A CN103234962A (en) 2013-05-09 2013-05-09 Vaginal micro-ecological environment sensor and manufacturing method thereof
CN2013101705804 2013-05-09
PCT/CN2014/070289 WO2014180172A1 (en) 2013-05-09 2014-01-08 Biochip and application thereof

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CN205449989U true CN205449989U (en) 2016-08-10

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CN201490000637.4U Expired - Fee Related CN205449989U (en) 2013-05-09 2014-01-08 Biochip

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WO (1) WO2014180172A1 (en)

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CN107677838A (en) * 2017-08-10 2018-02-09 深圳市金大精密制造有限公司 Detect integrated chip and its detection method
CN115452815A (en) * 2022-09-15 2022-12-09 武汉高芯科技有限公司 MEMS sensor with detection function and detection system

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CN107677838A (en) * 2017-08-10 2018-02-09 深圳市金大精密制造有限公司 Detect integrated chip and its detection method
CN115452815A (en) * 2022-09-15 2022-12-09 武汉高芯科技有限公司 MEMS sensor with detection function and detection system

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WO2014180172A1 (en) 2014-11-13

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