TR201612821A2 - NANOPOLYMER COATED ELECTRODE CONTAINING BIOSENSOR AND ELECTRODE COATING METHOD FOR FETAL RHD DETERMINATION FOR NONINVASIVE PRENATAL DIAGNOSIS - Google Patents
NANOPOLYMER COATED ELECTRODE CONTAINING BIOSENSOR AND ELECTRODE COATING METHOD FOR FETAL RHD DETERMINATION FOR NONINVASIVE PRENATAL DIAGNOSIS Download PDFInfo
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Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/80—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood groups or blood types or red blood cells
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
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- G01N33/54366—Apparatus specially adapted for solid-phase testing
- G01N33/54373—Apparatus specially adapted for solid-phase testing involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
- G01N33/5438—Electrodes
Abstract
Buluş; Rh uyuşmazlığı olan gebelerde, gebeliğin ilk 3 aylık erken döneminde, fetüse ait RhD antijenleri varlığının anne kanında tespit edebilen bir biyosensör ile ilgilidir.Meet; It is about a biosensor that can detect the presence of RhD antigens belonging to the fetus in the maternal blood in pregnant women with Rh incompatibility, in the early period of the first 3 months of pregnancy.
Description
TARIFNAME NONINVAZIV PRENATAL TANIYA YÖNELIK FETAL RHD TAYINI IÇIN NANOPOLIMER ILE KAPLANIVIIS ELEKTROT IÇEREN BIYOSENSÖR VE ELEKTROT KAPLAMA YÖNTEMI TEKNIK ALAN Bulus; Rh uyusmazligi olan gebelerde, gebeligin ilk 3 aylik erken döneminde, fetüse ait RhD antijenleri varliginin anne kaninda tespit edebilen bir biyosensör ile ilgilidir. ÖNCEKI TEKNIK Kaninda Rh antijeni bulunmayan kisiler Rh negatif (-), Rh antijeni bulunanlar kisiler ise Rh pozitif (+) olarak tanimlanmaktadir. Rh uyusmazliginin gerçeklesmesi için öncelikli sart annenin RhD (-) ve fetusun RhD (+) kan grubuna sahip olmasidir. Ek olarak, annenin bagisiklik sistemini tetikleyecek miktarda fetal eritrositinin, annenin kan dolasimina karismasi sarttir. D antijeni tasiyan fetal eritrositlere karsi anne kaninda anti-D antikorlari olusmasi halinde ise Rh uyusmazligindan söz edilir. Eger bu izoimmünizasyonun olusumu engellenemezse, sonraki gebeliklerde RhD (+) fetüslerde plasentadan fetüse geçen anti-RhD antikorlarinin fetal eritrositlerde yikima yol açmasi sonucu olusan “yenidoganin hemolitik hastaligi” ortaya çikar. Hastaligin siddeti degiskendir ve yenidogan ölümü ile sonuçlanabilir. Bu hastaliktan korunma yöntemi olan antenatal RhD proflaksisi (anti-D immünoglobini uygulamasi) bagisiklik riskini en aza indirmektedir. Yenidoganin hemolitik hastaligini önlemek amaciyla RhD (-) olan tüm gebelere rutin olarak anti-D immünoglobini uygulanmaktadir. Bu yöntemin her ne kadar uygun maliyetli oldugu düsünülse de, birçok ülkede -bizim ülkemiz de dahil- bu tedavi seçici olmadan tüm RhD (-) gebelere uygulandigindan maliyet oldukça yükselmektedir. Pek çok Ülkede rutinde kullanilan dogum öncesi anti-D proflaksisi ile RhD alloimmünizasyonunda azalma gözlenmektedir. RhD (-) annelerin bebeginin RhD (+) olma olasiligi yaklasik % 60 oldugu düsünülürse, bu annelerin % 40”inda bu uygulama gereksiz görülmekte ve kan ürünleri ile bulasan hastalik riskini de artirmaktadir. DESCRIPTION FOR THE DETERMINATION OF FETAL RHD FOR NONINVAZIV PRENATAL DIAGNOSIS BIOSENSOR CONTAINING KAPLANIVIIS ELECTRODE WITH NANOPOLYMER AND ELECTRODE COATING METHOD TECHNICAL FIELD Meet; In pregnant women with Rh incompatibility, early in the first 3 months of pregnancy During pregnancy, the presence of fetal RhD antigens can be detected in the mother's blood. It's about the biosensor. PRIOR ART People who do not have Rh antigen in their blood are Rh negative (-), Rh antigen Those who are found are defined as Rh positive (+). Rh incompatibility The primary condition for its realization is RhD (-) blood of the mother and RhD (+) blood of the fetus. group has. In addition, it will trigger the mother's immune system It is essential that a large amount of fetal erythrocytes enter the mother's blood circulation. D antigen If anti-D antibodies occur in maternal blood against fetal erythrocytes Rh incompatibility is mentioned. If the occurrence of this isoimmunization If it cannot be prevented, in subsequent pregnancies, RhD (+) fetuses are transferred from the placenta to the fetus. As a result of the passing of anti-RhD antibodies causing destruction in fetal erythrocytes “Hemolytic disease of the newborn” occurs. Severity of the disease is variable and may result in neonatal death. Prevention from this disease antenatal RhD prophylaxis (anti-D immunoglobin administration) minimizes the risk of immunity. Hemolytic disease of the newborn Anti-D immunoglobin is routinely administered to all pregnant women with RhD (-) to prevent is being implemented. Although this method is considered to be cost-effective In many countries, including our country, this treatment is non-selective for all RhD (-) Since it is applied to pregnant women, the cost is quite high. In Many Countries RhD with routine prenatal anti-D prophylaxis A decrease in alloimmunization is observed. baby of RhD (-) mothers Considering that the probability of being RhD (+) is approximately 60%, % of these mothers At 40, this practice is deemed unnecessary and the disease can be transmitted by blood products. also increases the risk.
Gebe kalma ve dogum sancisi arasinda geçen süreye prenatal dönem denmektedir. Prenatal dönemde, fetal RhD durumunun belirlenmesi ile yenidoganin hemolitik hastaligi riski göze alinmaksizin, RhD (+) bebege sahip oldugu tespit edilen RhD (-) annelerin gereksiz olarak anti-D immünoglobini ile immünizasyonu engellenebilir. Prenatal tani yöntemlerinde kullanilan fetal genetik materyal, geleneksel olarak amniyosentez veya koriyonik villüs örneklemesi ile elde edilir. Ancak, bu invaziv (Cilt bütünlügünü bozan islemlere verilen genel isim) örnekleme yöntemlerinde yaklasik % 1 oraninda düsük gözlenebilmektedir. Ayrica islem, fetomaternal kanama ile komplike oldugunda, annede RhD izoimmünizasyonun gelismesine de yol açabilmektedir. Prenatal period to the period between conception and labor pain it is called. In the prenatal period, with the determination of fetal RhD status Having a RhD (+) baby, regardless of the risk of hemolytic disease of the newborn RhD (-) mothers, who were found to be immunization can be prevented. Fetal used in prenatal diagnosis methods genetic material, traditionally amniocentesis or chorionic villus obtained by sampling. However, this invasive the general name given) is about 1% low in sampling methods. can be observed. Also, when the procedure is complicated by fetomaternal hemorrhage, It can also lead to the development of RhD isoimmunization in the mother.
Dolayisiyla, RhD uyusmazligi söz konusu oldugunda risk-yarar dengesi kurulursa, rutin anti-D immünoglobini uygulanmasi invaziv tani yöntemlerinden daha agir basmaktadir. Bu dengeyi degistirmenin tek yolu invaziv olmayan tani yöntemlerinin gelistirilmesidir. Therefore, the risk-benefit balance is in question when it comes to RhD incompatibility. established, routine administration of anti-D immunoglobin is one of the invasive diagnostic methods. presses harder. Non-invasive diagnosis is the only way to change this balance. development of methods.
Mevcut riskleri nedeniyle invaziv prenatal tani yöntemlerine alternatif olusturabilecek invaziv olmayan (non-invaziv) yöntemlerin bulunmasi son yillarda yapilan çalismalarda arastirmacilarin hedefi haline gelmistir. Plasenta fizyolojisinin daha iyi anlasilmasi bu sorunun çözülmesine ilham kaynagi olmustur. Yapilan çalismalarda, plasentanin anneden fetusa dogru tek yönlü geçisi saglayan bir bariyer oldugu kabul edilen popüler görüsün aksine, plasentanin çift yönlü trafige izin veren bir bariyer oldugu görüsü desteklenmektedir. Bu çalismalarda, saglam fetal hücrelerin ve hücre disi serbest fetal nükleik asitlerin plasentayi geçebildigi ve anne kaninda tespit edilebildigi gösterilmistir. 1997'de L0 ve arkadaslari gebelerin kaninda bulunan serbest fetal DNA'nin (cffDNA) %3-6 kadarinin fetüse ait oldugunu göstermislerdir. Annenin periferik kanindan fetal genetik materyalin ekstraksiyonu ve analizi, invaziv olmayan bir tani yönteminin kapisini aralamistir. Alternative to invasive prenatal diagnosis methods due to existing risks Finding non-invasive (non-invasive) methods that can It has become the target of researchers in studies conducted over the years. Placenta A better understanding of its physiology will inspire solving this problem. has been. Studies have shown that placenta is unidirectional from mother to fetus. Contrary to popular opinion, which is accepted as a barrier to The view that the placenta is a barrier that allows two-way traffic is supported. In these studies, intact fetal cells and extracellular that free fetal nucleic acids can cross the placenta and are detected in maternal blood. has been shown to be possible. In 1997, L0 et al. 3-6% of free fetal DNA (cffDNA) belongs to the fetus. they have shown. Fetal genetic material from the mother's peripheral blood extraction and analysis opens the door to a non-invasive diagnostic method intertwined.
Yapilan arastirmalarla anne kanindan, annede bulunmayip fetüste yer alan belirteçler yardimiyla cffDNAinin varligi gösterilmistir. Bu belirteçler arasinda erkek fetüs tasiyan annelerde Y kromozomu varligi ve RhD (-) annelerde fetüse ait RhD'nin gösterilmesi yer almaktadir. Bu çalismalarda anne kani plazma veya serumundan elde edilen CffDNA yüksek hassasiyet ve özgüllükteki gerçek zamanli (real-time) PCR yöntemi ile RhD geninin farkli bölgeleri hedef alinarak fetal RHD tayini yapilmistir. Son dönemlerde Avrupa'nin bazi ülkelerinde fetal RhD tayini rutin uygulamada kullanilmaktadir. According to the researches, it is obtained from the mother's blood, not in the mother but in the fetus. The presence of cffDNA was shown with the help of domain markers. These markers The presence of Y chromosome and RhD (-) in mothers carrying male fetuses demonstration of fetal RhD in mothers. In these studies, mother CffDNA obtained from blood plasma or serum is highly sensitive and Differentiation of RhD gene with real-time PCR method with specificity Fetal RHD determination was made by targeting the regions. lately Fetal RhD determination is used in routine practice in some European countries.
Testlerin uygulamasi gerçek zamanli PCR teknigi ile yapilmakta; bir kisim gebeligin ikinci 3 aylik döneminde uygulanirken, son dönemlerde gebeligin erken dönemlerinde de basari ile uygulanmaktadir. Application of tests is done with real-time PCR technique; a part While it is applied in the second trimester of pregnancy, it is used in the last periods of pregnancy. It is also successfully applied in the early stages.
Bir Türk patentinde RhD geni 4. Ekson bölgesine özgü bir real-time PCR yöntemi, 8 haftalik gebelerde anne kanindan ayrilan plazmadan elde edilen CffDNA ile fetal RhD tayini yöntemini anlatilmaktadir. Bu bulus ile gelistirilen yöntem 8 haftalik gebelere uygulanabilmektedir. Erken dönemde teshisin yapilabilmesi hastaligin önlenmesinde gerekli tedaviye erken baslamayi saglamaktadir. Noninvaziv olarak uygulanan gerçek zamanli PCR yöntemi, invaziv yöntemlere göre güvenilirligi yüksek ve hizli bir yöntem olmasi ve erken dönemde uygulanabilmesi özelligi ile avantajli bir yöntemdir. Noninvaziv prenatal taniya yönelik bu yöntemlerin yüksek maliyetli olmasi, test öncesi örnek için ön hazirlik evresinin ve DNA izolasyon asamasinin olmasi ve sonuç çikana kadar geçen sürenin 1.5 - 2 saati geçmesi gerekmektedir. Bu yöntemlere göre dakikada sonuç verebilen, çok daha az örnek kullanimi (direk kandan analiz, sulandirma disinda ön islem gerektirmeden) gerektiren ve PCR yöntemine göre çok düsük maliyetli analiz yöntemi olan biyosensörler bu yönteme alternatif olarak düsünülebilir. Biyosensörler fizikokimyasal analiz sistemleri ve biyolojik materyallerin birlestirilmesi ile olusan analitik sistemlerdir. A real-time PCR specific to the RhD gene Exon 4 region in a Turkish patent. method, obtained from the plasma separated from the mother's blood in 8 weeks pregnant. The method of fetal RhD determination with cffDNA is described. Developed with this invention The method can be applied to 8 weeks pregnant women. Early diagnosis It is possible to start the necessary treatment early in the prevention of the disease. it provides. Real-time PCR method applied noninvasively, It is a fast and reliable method compared to invasive methods and it It is an advantageous method with its feature of being applied in the period. noninvasive The high cost of these methods for prenatal diagnosis, Presence of the preliminary preparation phase and DNA isolation phase for the sample and the result The time until the exit should exceed 1.5 - 2 hours. to these methods less sample usage (direct blood analysis, without preprocessing other than dilution) and PCR Biosensors, which are very low-cost analysis methods compared to the can be considered as an alternative method. Biosensors physicochemical analysis They are analytical systems formed by combining systems and biological materials.
Biyosensörlerde, biyolojik sistemin yüksek özgüllügü ile fiziksel analiz sisteminin tayin duyarliligi bilestirilmistir. Çok sayida biyoorganik molekül ve bazi inorganik moleküllerin analizinde kullanmak amaci ile pek çok biyosensör gelistirilmistir. In biosensors, the high specificity of the biological system and the physical analysis system detection sensitivity is compounded. Numerous bioorganic molecules and some inorganic Many biosensors have been developed for use in the analysis of molecules.
Günümüzde biyosensörler, özellikle saglik alani basta olmak üzere; çevresel analizlerde, askeri sahada, gida, farmasötik ve kimya endüstrilerinde kullanilmaktadir. Biyosensör teknolojisi ile fetal DNA kullanilarak cinsiyet tayini yapan bir yöntem bildirilmistir. Bu yöntemde anne kanindan plazmayi ayirip burada bulunan fetal DNA°yi elde ettikten sonra cinsiyet analizi gerçeklestirmistir. Today, biosensors, especially in the field of health; environmental analysis, military, food, pharmaceutical and chemical industries is used. Sex determination using fetal DNA with biosensor technology A method has been reported. In this method, we separate the plasma from the mother's blood and gender analysis after obtaining the fetal DNA found here has realized.
BULUSUN KISA AÇIKLAMASI Bulus, direk anneden alinan kana, antijen antikor baglanma esasina dayanarak uygulanan biyosensör ile ilgilidir. Bulus ile diger yöntemlere göre (plazma ayrimi ve DNA eldesi kullanan yöntemler) daha kisa sürede sonuç alinarak, çok daha düsük maliyetlerle islem gerçeklestirilebilmektedir. Alinan sonuçlar, fetal DNA'dan gerçek zamanli PCR yöntemi ile de dogrulanmistir. Bu sekilde gebeligin ilk haftalarinda tespit edilen fetal RhD sayesinde, RhD negatif annenin antikor taramasi için belirli dönemlerde hastaneye gidip test yaptirmasi (Indirek Coombs testi) gerekmemektedir. BRIEF DESCRIPTION OF THE INVENTION The invention is based on the antigen-antibody binding to the blood taken directly from the mother. based on the applied biosensor. According to the invention and other methods (methods using plasma separation and DNA extraction) result in a shorter time The transaction can be carried out at much lower costs. received The results were also confirmed by real-time PCR from fetal DNA. This Thanks to fetal RhD detected in the first weeks of pregnancy in this way, RhD negative for the mother to go to the hospital at certain times to have a test for antibody screening (Indirect Coombs test) is not required.
SEKILLERIN ANLAMI Sekil 2. Elektrodun Biyoaktif Tabakasina Baglanma Prensibini Anlatan Akis Semasi Sekiller de belirtilen parça numaralarinin karsiliklari asagida verilmistir. MEANING OF SHAPES Figure 2. The Bonding Principle of the Electrode to the Bioactive Layer Narrative Flow Sema The corresponding part numbers in the figures are given below.
Elektrot Ölçme Tusu Açma/Kapama Tusu a) Hema-MAC (2-hidroksietil metakrilat metakroilamidosistein) nanopolimeri ) Glutar Aldehit Ve Anilinden En Az Biri c) Anti RhD ) `Jelatin BULUSUN DETAYLI AÇIKLAMASI Bulus, fetal RhD tayini yapmak için gelistirilmis immünolojik bir sensördür. Gelistirilen bu sensör, anne kanindaki fetal RhD antijenlerinin elektrokimyasal olarak varliginin tayin edilmesini saglamaktadir. Bunun için, biyoaktif tabakasi anti-RHD ile kaplanmis altin çalisma elektrotu (1) kullanilmaktadir. Baglanma antijen-antikor esasina dayanarak gerçeklesmektedir. Elektrotun (1) biyoaktif tabakasina antikor baglanma prensibi ve alinan sinyal düzeyleri Sekil 2'de akis semasi üzerinde gösterilmistir. Electrode Measuring Key On/Off Key a) Hema-MAC (2-hydroxyethyl methacrylate methacrylamidocysteine) nanopolymer ) At least one of glutar aldehyde and aniline c) Anti RhD ) `Gelatin DETAILED DESCRIPTION OF THE INVENTION The invention is an immunological instrument developed for fetal RhD determination. is the sensor. This developed sensor detects fetal RhD antigens in maternal blood. It allows the determination of its presence electrochemically. For this, gold working electrode (1) coated with a bioactive layer of anti-RHD is used. Binding is based on antigen-antibody basis. is taking place. Antibody binding to the bioactive layer of the electrode (1) principle and received signal levels are shown in Figure 2 on the flow diagram. shown.
Fiziksel ve kimyasal olarak yüzeyi temiz bir altin çalisma elektrotu (1) yüzeyine eklenen Hema-MAC (2-hidroksietil metakrilat metakroilamidosistein) nanopolimeri (a), jelatin (d) ve sistein rezidüleri üzerinden altin elektrot yüzeyi ile shift bazi olusturmaktadir. Nanopolimer ile modifiye edilmis çalisma elektrotu (1) üzerine anti-RhD (c) antikorlarinin baglanabilecegi çapraz baglayici ajanlar olan glutar aldehit ve anilinden en az biri (b), elektrot (1) yüzeyindeki nanopolimere baglanir. Modifiye elektrot (1) üzerine son olarak anti-RhD (c) antikoru eklenir. Antikor agir zinciri, glutar aldehit ve anilinden en az biri (b) üzerinden baglanmaktadir. Siralanan islemler gerçeklestirildikten sonra elektrot (1), RhD (e) antijenine spesifik olarak elektrokimyasal ölçüm gerçeklestirmeye hazirdir. A physically and chemically clean gold working electrode (1) Hema-MAC (2-hydroxyethyl methacrylate methacrylamidocysteine) added to the surface gold electrode surface over nanopolymer (a), gelatin (d) and cysteine residues with shift base. Working electrode modified with nanopolymer (1) cross-linking agents on which anti-RhD (c) antibodies can bind At least one of the glutar aldehyde and aniline (b) on the electrode (1) surface bound to the nanopolymer. Finally, anti-RhD (c) on the modified electrode (1) antibody is added. At least one of the antibody heavy chain, glutar aldehyde, and aniline (b) is connected via. After performing the listed operations, the electrode (1) to perform an electrochemical measurement specific to the RhD(e) antigen. is ready.
Yukarida kaplanma yöntemi anlatilan elektrotun (1) yüzeyindeki ölçüm haznesine Rh uyusmazligi olan gebenin bir damla kani damlatildiginda; fetal antijenler modifiye elektrot (1) yüzeyindeki antikorlar ile baglanma göstermektedir. Bu baglanma cihazimizda bir sinyal olusmasina sebebiyet vermektedir. The measurement on the surface of the electrode (1), the coating method of which is described above when a drop of blood of a pregnant woman with Rh incompatibility is dripped into her reservoir; fetal antigens bind with antibodies on the surface of the modified electrode (1) shows. This connection causes a signal to occur in our device. gives.
Sistemde; öncelikle, üzerine bir nanoplimer (metakrilat ve benzeri) baglanmis olan altin çalisma elektrotunun üzerine Rh antikorlari, çapraz baglayici ajan olan glutar aldehit ve anilinden en az biri (b) kullanilarak çapraz baglanmistir. Sensör, Rh antikorlarinin elektrot (1) yüzeyine baglanmasi ile kan numunesi eklendiginde, Rh antikorlarina bir baglanma olmasi durumunda kalitatif ve kantitatif olarak ölçüm alinmasina olanak saglayacak sekilde dizayn edilmistir. In the system; first, a nanopolymer (methacrylate etc.) Rh antibodies on the connected gold working electrode, cross cross using at least one (b) of the binding agent glutar aldehyde and aniline is connected. The sensor is connected to the surface of the electrode (1) by Rh antibodies. sample is added, in case of a binding to Rh antibodies It is designed to allow qualitative and quantitative measurements to be taken. has been made.
Cihazin ölçüm prensibi, maternal kanda bulunan Fetal Rh antijeninin, elektrot (1) üzerindeki Rh antikoru ile gösterdigi reaksiyonun sebep oldugu elektrik akiminin ölçülmesi esasina dayanir. Genel bir yaklasimla, bir AC sinüs dalgasi üreteoi ile üretilen AC sinüs dalgasi ve bir DC voltaj kaynagi ile üretilen DC polarizasyon voltaji bir birlestirici vasitasi ile birlestirilmistir. Biyosensör elektrotu üzerinde antijen ile antikor baglanmasi sirasinda, etkin direnç ve kapasitansi yansitan bir sinyal olusturmak üzere biyosensör elektrotuna numune (kan) tatbik edilmektedir. Ek olarak, AC sinüs dalgasi, sinüs dalgasi ile es zamanli olan kare dalga üreten bir kare dalga üretecine geçirilmektedir. The measurement principle of the device is that Fetal Rh antigen in maternal blood, caused by the reaction with the Rh antibody on the electrode (1). It is based on the measurement of electric current. In a general approach, an AC sine The AC sine wave generated by the wave generator and the DC voltage source produced by the The DC polarization voltage is coupled via a combiner. biosensor During antigen and antibody binding on the electrode, effective resistance and to the biosensor electrode to generate a signal that reflects the capacitance. sample (blood) is administered. In addition, the AC sine wave is combined with the sine wave. It is passed to a square wave generator that produces a synchronous square wave.
Biyosensör hücresinde olusan sinyal, sinyali bir voltaj sinyaline dönüstürmek için akim-voltaj (I/V) dönüstürücüden geçirilmektedir. Voltaj (I/V) dönüstürücüden çikan voltaj sinyalinin fazi, faz degistirici tarafindan degistirilmektedir. Faz degistiricisinin çiktisi, demodüle edilmis bir sinyal olusturmak üzere kare dalga üretecinin çiktisinin kullanildigi demodulasyon için bir senkron modülatöre geçirilmektedir. Demodüle edilen sinyal, Rh antijeni varliginda, Rh antijeni miktari ile dogru orantili olan bir sinyal olusturmak üzere bir alçak geçis filitresinden geçirilmektedir. Sinyal A/D (Analogdan dijitale) dönüstürücü ile dijitale dönüstürülür ve dijital sinyal, biyosensör elektrotu üzerindeki etkin kapasitansa dayanilarak numune (kan) içerisinde fetusun Rh antijeninin varligini ve miktarini belirlemek için islemciye aktarilarak, islemci tarafindan islenip ekrana fetusun Rh pozitif veya negatif oldugu hakkinda bilgi vermektedir. Mevcut bulus kan uyusmazligi olan Rh negatif annelerin bebeklerinin Rh grubu tayinin yapilmasi açisindan yararlidir. Ölçüm cihazi reaksiyon sirasinda olusan akimi degisimini ölçer ve bu akim degisim degerine karsilik gelen Fetal Rh antijeni seviyesini gösterir. Yukarida belirtilen tüm islemler, cihaz dahilindeki parça ve birimler araciligiyla gerçeklestirilmektedir. The signal formed in the biosensor cell is to convert the signal into a voltage signal. It is passed through a current-to-voltage (I/V) converter. Voltage (I/V) The phase of the voltage signal coming out of the converter is changed by the phase changer. is being changed. The output of the phase shifter is a demodulated signal. For demodulation, where the output of the square wave generator is used to generate is passed to a synchronous modulator. Demodulated signal, Rh antigen in its presence, to generate a signal that is directly proportional to the amount of Rh antigen. passed through a low pass filter. Signal A/D (Analog to digital) It is converted to digital by the converter and the digital signal is transferred to the biosensor electrode. Rh of the fetus in the sample (blood) based on the effective capacitance on transferred to the processor to determine the presence and amount of antigen information about whether the fetus is Rh positive or negative on the screen. gives. The present invention is in Rh negative mothers with blood incompatibility. It is useful for determining the Rh group of babies. measuring device It measures the current change that occurs during the reaction and this current changes value. indicates the corresponding Fetal Rh antigen level. All mentioned above Operations are carried out through the parts and units within the device.
Bu bulus, kapsamli laboratuvar sartlarinin yaninda, uzman uygulayici gerektiren, uzun zaman alan ve yüksek maliyetli kimyasal maddeler kullanilarak yapilan fetal Rh tayinini islemini, her kosulda, okuma yazma kabiliyetine sahip herhangi bir kimsenin uygulayabilecegi oldukça ucuz ve hizli bir sekilde yapilmasina olanak saglamasi açisindan faydalidir. Besides extensive laboratory requirements, this invention using chemicals that require a long time and costly the fetal Rh determination process, in all conditions, with the ability to read and write. in a fairly cheap and fast way that anyone can implement It is useful in terms of enabling it to be done.
Cihazin kullanimi, Sekil ilde 1 numara ile gösterilen elektrot cihaza sekildeki gibi takilmasi, açma/kapama tusuna (4) basilarak açildiktan sonra venöz kandan alinan 1 damla örnek elektrot üzerinde bulunan örnek uygulama haznesine damlatilip ölçme tusuna (3) basilarak antijen-antikor baglanmasi sonucu akim degisimi olup olmamasina göre sonuç vermektedir. Sonuç pozitif ise Ekranda +, negatif ise ekranda - simgesi gözlenmektedir. Daha sonra Cihaz kapatilip, elektrot ilik su ile temizlenip tekrar kullanim için saklanilabilmektedir. Using the device, the electrode shown with number 1 in the figure is attached to the device. after it is turned on by pressing the on/off button (4). Sample application on 1 drop of sample electrode taken from venous blood antigen-antibody binding by dripping into the chamber and pressing the measuring button (3) The result gives results according to whether there is a current change or not. Result positive If it is negative, the + symbol is observed on the screen, and if it is negative, the - symbol is observed on the screen. Later Device it can be closed, the electrode can be cleaned with lukewarm water and stored for reuse.
Rh sensörünün elektrot (1) yüzeyi nanopolimere, glutar aldehit ve anilinden en az biri olan çapraz baglayici ajan yardimiyla bagli Rh antikoru içermektedir. Nanopolimer kullanimindan dolayi elektrotlar (1) çoklu kullanima elverislidir.The electrode (1) surface of the Rh sensor is made of nanopolymer, glutar aldehyde and Rh antibody bound by means of a cross-linking agent that is at least one of aniline contains. Due to the use of nanopolymer, the electrodes (1) are multi-use it is convenient.
Claims (1)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2016/12821A TR201612821A2 (en) | 2016-09-08 | 2016-09-08 | NANOPOLYMER COATED ELECTRODE CONTAINING BIOSENSOR AND ELECTRODE COATING METHOD FOR FETAL RHD DETERMINATION FOR NONINVASIVE PRENATAL DIAGNOSIS |
| PCT/TR2017/050422 WO2018070968A2 (en) | 2016-09-08 | 2017-09-08 | Nanopolimer coated electrostatic bioesensor and electrostatic coating method for noninvasive prenatal diagnosis of fetal rhd |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2016/12821A TR201612821A2 (en) | 2016-09-08 | 2016-09-08 | NANOPOLYMER COATED ELECTRODE CONTAINING BIOSENSOR AND ELECTRODE COATING METHOD FOR FETAL RHD DETERMINATION FOR NONINVASIVE PRENATAL DIAGNOSIS |
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