TR202021834A2 - A CUSTOMIZED BIOSENSOR DEVICE AND PATHOGEN DETECTION METHOD FOR FRET TECHNIQUE - Google Patents
A CUSTOMIZED BIOSENSOR DEVICE AND PATHOGEN DETECTION METHOD FOR FRET TECHNIQUEInfo
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Abstract
Buluş, FRET tekniği için özelleştirilmiş optik temelli olarak patojenlerin tespit edilmesine imkân veren bir biyosensör cihazı (10) ile ilgilidir. Bir biyosensör cihazına (10) özel olarak geliştirilen patojen tespit çipi (40) üzerinden dinamik olarak FRET sinyali alınması ve bu sayede patojenlerin 10 saniye gibi kısa bir süre içerisinde tespit edilmesi sağlanmaktadır. Bir hastadan alınan örnek, özel bir solüsyonla karıştırıldıktan sonra patojen tespit çipi (40) üzerine damlatılarak biyosensör cihazı (10) tarafından ortamda patojen varsa FRET sinyali alınarak tespit edilmektedir.The invention relates to a biosensor device (10) that allows the detection of pathogens on an optical basis, customized for the FRET technique. FRET signal is received dynamically via the pathogen detection chip (40) specially developed for a biosensor device (10), and thus pathogens are detected in as little as 10 seconds. After the sample taken from a patient is mixed with a special solution, it is dripped onto the pathogen detection chip (40) and detected by the biosensor device (10) by receiving the FRET signal if there is a pathogen in the environment.
Description
TARIFNAME FRET TEKNIGI IçIN ÖZELLESTIRILMIS BIR BIYOSENSÖR CIHAZI VE PATOJEN TESPIT YÖNTEMI Bulus, FRET (Förster Resonance Energy Transfer) teknigi Için özellestirilmis optik temelli olarak patojenlerin tespit edilmesine imkân veren bir biyosensör cihazi ile ilgilidir. DESCRIPTION A BIOSENSOR DEVICE CUSTOMIZED FOR FRET TECHNIQUE AND PATHOGEN DETECTION METHOD The invention is based on a specialized optic for the FRET (Förster Resonance Energy Transfer) technique. It relates to a biosensor device that allows the detection of pathogens.
Daha belirgin olarak mevcut bulus; bir biyosensör cihazina özel gelistirilen farkli dalga boylarinda enerjiye sahip floresan moleküllerin ayni hedefte (patojen) bir araya gelmesini saglayan, böylece iki molekül arasinda meydana gelen FRET olayi sonucunda açiga çikan emisyon optik güç degerlerindeki degisime bakilarak mikrobiyolojik yapinin kesin varligi hakkinda hükme varilmasina olanak veren tek kullanimlik patojen tespit çipi üzerinden dinamik olarak FRET sinyali (isimasi) alinmasi ve bu sayede patojenlerin 10 saniye gibi kisa bir süre içerisinde tespit edilmesini saglayan bir yöntemle ilgilidir. More specifically, the present invention; at different wavelengths specially developed for a biosensor device. which enables fluorescent molecules with high energy to come together on the same target (pathogen), so that two Emission optical power released as a result of FRET event occurring between molecules It is necessary to make a decision about the definitive existence of the microbiological structure by looking at the change in the values of the microbiological structure. FRET signal (name) dynamically via a disposable pathogen detection chip that allows and thus detecting pathogens in a short time like 10 seconds. It's about a method.
Teknigin Bilinen Durumu Patojenler, canlilarin hücrelerinde çogalabilen ve enfeksiyona sebep olan biyolojik varliklardir. State of the Art Pathogens are biological entities that can multiply in the cells of living things and cause infection.
Patojenlerin önemli bir bölümü, örnegin virüsler, normal bir mikroskop ile görülmek için çok küçük yapidadir. Patojenlerin boyutu genellikle nanometre cinsinden ölçülmektedir. Bir influenza A virüsü incelenecek olursa 80-120 nm boyutunda oldugu anlasilmaktadir. Birçok türe sahip olan virüsler; Insanlar, bitkiler, bakteriler ve algler gibi her türlü yasam formuna bulasarak çesitli hastaliklara sebep olmaktadirlar. Bu sebeple virüsler basta olmak üzere patojenlerin hassas ve seçici olarak tespit edilmesi oldukça önem tasimaktadir. Özellikle yeni korona virüsün (Covid-19) dünya genelini etkilemesi nedeniyle hizli bir sekilde tespit edilmesi Ihtiyaci dogmustur. Ates, öksürük, bogaz agrisi gibi üst ve alt solunum yolu enfeksiyonuna benzer semptomlar gösterilmesine neden olan C0vid-19 virüsünün hizli ve pratik bir sekilde ayirt edilmesi gerekmektedir. Covid-19 virüsünün hizli tespit edilmesi hastaya uygun tedavi yöntemlerinin uygulanmasi Için önemlidir. Buna ek olarak, Covid-19'un hayatimiza girmesiyle beraber, Ise giris ya da seyahat öncesinde de virüs testi istenmektedir. Söz konusu testlerin sonucuna bagli olarak islem yapilmasi nedeniyle hizli ve dogru sonuç veren tespit yöntemleri uygulanmalidir. A significant proportion of pathogens, such as viruses, are too small to be seen with a normal microscope. is in the structure. The size of pathogens is usually measured in nanometers. an influenza A virus If it is examined, it is understood that it is 80-120 nm in size. Viruses with many types; It causes various diseases by infecting all kinds of life forms such as humans, plants, bacteria and algae. they are. For this reason, sensitive and selective detection of pathogens, especially viruses is of great importance. Especially since the new corona virus (Covid-19) affects the whole world, it is quickly detected. The need to be done has arisen. Upper and lower respiratory tract infections such as fever, cough, sore throat quickly and practically distinguish the C0vid-19 virus, which causes similar symptoms. needs to be done. Rapid detection of the covid-19 virus, appropriate treatment methods for the patient important for its implementation. In addition, with the entry of Covid-19 into our lives, A virus test is also requested before travel. Depending on the results of the said tests, the process Fast and accurate fastening methods should be applied due to the
Teknolojinin hizla ilerlemesiyle beraber virüs, bakteri gibi gözle görülmeyen mikroorganizmalarin tespit edilmesi kolaylasmistir. Genellikle PCR (polimeraz zincir reaksiyonu) amplifikasyonu ve floresan algilamaya yönelik çesitli patojen tespit yöntemleri mevcuttur ancak mevcutta kullanilan yöntemler 10 saniye gibi bir sürede hizli sonuç veren bir yöntem sunmamaktadir. saptanmasina yönelik bir yöntem ve kitten bahsedilmektedir. Söz konusu yöntem; gerekirse oDNA'ya dönüstürüldükten sonra ilgilenilen nükleik asidin amplifikasyonunun yapilmasini içermektedir. With the rapid progress of technology, invisible microorganisms such as viruses and bacteria easier to detect. Usually PCR (polymerase chain reaction) amplification and There are various pathogen detection methods for fluorescence detection, but currently used methods do not offer a method that gives fast results in 10 seconds. A method and kit for detection are mentioned. The method in question; to oDNA if needed It involves amplification of the nucleic acid of interest after it has been transformed.
Sonrasinda ise amplifiye edilmis nükleik asit, gerçek zamanli PCR (RT-PCR) teknigi ile daha fazla amplifikasyon için sablon olarak kullanilmaktadir. Ancak burada, patojenlerin hizli bir sekilde tespit edilmesi için kullanilan optik temelli bir biyosensörden bahsedilmemektedir. Afterwards, the amplified nucleic acid is further processed by real-time PCR (RT-PCR) technique. It is used as a template for amplification. Here, however, the rapid detection of pathogens There is no mention of an optical-based biosensor used for
CN1690691 nolu patent dokümaninda SARS korona virüs SCL'nin proteazi için bir aktivite saptama ve inhibitör tarama yönteminden bahsedilmektedir. Buna göre; SARS korona virüs SCL'nin proteaz florojenik substratinin olusturulmasi, substratin reaksiyon tamponu sivisiyla karistirilmasi ve bir kosulda etkinlestirmek için SCL proteaz eklenmesi saglanmaktadir. SARS korona virüs SCL proteazin floresan degerinin çesitliligini tespit edilerek in vitro aktivite tespitinin tamamlanmasi saglanmaktadir. 3CL proteaz ve mikro moleküler bilesigi inkübe edilerek bazi durumlarda saptama için beklenip, florojenik substrat ile karistirilmaktadir. iletilen dalganin dalga boyu ile floresans degerinin tespit edilerek BCL proteaz eklenmis mikro moleküler bilesigin aktivitesi belirlenmektedir. Iki deger karsilastirilarak mikro moleküler bilesigin 3CL proteaz ile aktivite inhibisyon orani hesaplanmaktadir. Detection of an activity for the protease of SARS coronavirus SCL in patent document CN1690691 and inhibitor screening method are mentioned. According to this; protease of SARS coronavirus SCL formation of the fluorogenic substrate, mixing the substrate with the reaction buffer liquid and Addition of SCL protease is provided to activate the condition. SARS coronavirus SCL proteazine By detecting the variety of fluorescence value, in vitro activity determination is completed. 3CL protease and micromolecular compound incubated and in some cases waiting for detection, mixed with the fluorogenic substrate. Determination of the wavelength of the transmitted wave and the fluorescence value The activity of the micromolecular compound with BCL protease added is determined. two values By comparison, the rate of activity inhibition of the micromolecular compound with 3CL protease is calculated.
Dolayisiyla burada, bir biyosensöre özel olarak gelistirilen bir patojen tespit çipi üzerinden dinamik olarak FRET sinyali alinmasi ve bu sayede patojenlerin 10 saniye gibi kisa bir süre içerisinde tespit edilmesini saglayan bir yöntemden bahsedilmemektedir. bahsedilmektedir. Buna göre söz konusu yöntem; tespit edilecek bir örnegin RNA'sinin çikarilmasi, ters transkripsiyonun gerçeklestirilmesi ve ardindan bir amplifikasyon ürünü elde etmek için bir primer kullanilarak P'nin amplifiye edilmesi, amplifikasyon ürününün reaksiyon için bir ön karisimina eklenmesi ve reaksiyon ürününün saptanmasi islemlerini içermektedir. Ancak burada, floresan isaretli bir biyosensör kullanilmasindan bahsedilmemektedir. So here, dynamics is done via a pathogen detection chip specially developed for a biosensor. As a result, FRET signal is received and pathogens are detected in a short time like 10 seconds. There is no mention of a method to do so. is mentioned. Accordingly, the method in question; extracting the RNA of a sample to be detected, a primer to perform reverse transcription followed by an amplification product amplification of P using the amplification product to a premix for the reaction. addition and determination of the reaction product. But here, fluorescent There is no mention of using a marked biosensor.
Sonuç olarak teknigin bilinen durumlarinin yetersiz kalmasi; bir biyosensöre özel gelistirilen bir patojen tespit çipi üzerinden dinamik olarak FRET sinyali alinmasi ve bu sayede patojenlerin 10 saniye gibi kisa bir süre içerisinde tespit edilmesini gerçeklestirilmesine yönelik bir çözümü gerekli kilmistir. As a result, the known situations of the technique are insufficient; developed specifically for a biosensor. dynamically receiving FRET signal from the pathogen detection chip and thus A solution is required for detecting in a short time such as seconds. it is clay.
Bulusun Amaci ve Kisa Açiklamasi Bulusun amaci, FRET (Floresan Rezonans Enerji Aktarimi) teknigi için özellestirilmis optik temelli olarak patojenlerin tespit edilmesine imkân veren bir biyosensör cihazi ortaya koymaktir. Purpose and Brief Description of the Invention The aim of the invention is based on optics specialized for FRET (Fluorescent Resonance Energy Transfer) technique. The aim is to introduce a biosensor device that allows the detection of pathogens.
Bulusun bir baska amaci; bir biyosensör cihazina özel gelistirilen bir patojen tespit çipi üzerinden dinamik olarak FRET sinyali alinmasini ve bu sayede patojenlerin 10 saniye gibi kisa bir süre içerisinde tespit edilmesini saglayan bir yöntem ortaya koymaktir. Another purpose of the invention is; via a pathogen detection chip specially developed for a biosensor device dynamically receiving the FRET signal and thus pathogens in a short time like 10 seconds. It is to present a method that enables it to be detected in
Bulusun bir baska amaci; kompakt bir tasarima sahip ve dinamik ölçüm yapabilen FRET teknigi için özellestirilmis bir biyosensör cihazi ortaya koymaktir. Another purpose of the invention is; For FRET technique with a compact design and dynamic measurement is to introduce a customized biosensor device.
Bulus, patojenlerin tespit edilmesine imkân veren bir biyosensör cihazi olmak üzere; biyosensör cihazina iliskin islem sonucunun bildirilmesine imkan veren bir ekran, bir lazer diyot ile eslestirilmis bir optik fiber, bir optik fiberden çikan lazer isigin bir patojen tespit çipine yönlendirilmesini saglayan bir dalga boyu seçici ayna, bir biyosensör cihazi için özel olarak tasarlanmis bir patojen tespit çipi, bir optik fiberden çikan lazer isigi örnegin üst yüzeyine odaklayan bir mercek, bir optik fiberden çikan lazer isigin düzlem dalga haline getirilmesine imkan veren bir kolimasyon sistemi, isigin tespit edilmesinde kullanilan bir PMT sensör yüzeyi (70), FRET isimasi haricindeki dalga boylarinin sogurulmasina imkan veren bir seçici filtre (71), bir patojen tespit çipinin monte edildigi bir küvet gövdesi ve bir küvet gövdesine iliskin bir küvet kapagi bilesenleri vasitasiyla; - bir optik fiberden çikan lazer isigin düzlem dalga haline getirilmek üzere özel tasarim bir kolimasyon sistemi kullanilmasi, - bir optik fiberden çikan lazer isigi bir patojen tespit çipine yönlendirmek üzere bir dalga boyu seçici ayna kullanilmasi, - bahsedilen patojen tespit çipinin önünde bulunan mercegin optik fiberden çikan lazer isigi çip yüzeyine odaklamasi, - patojen tespit çipinde olusan floresan isimasinin bir kisminin optik fiberden çikan aydinlatma isiginin yolundan ve mercekte toplanacak sekilde geçmesi, - floresan isimasinin dalga boyunun seçici aynada yansimayip içinden geçerek PMT sensör yüzeyine ulasmasi, - PMT sensör yüzeyi öncesindeki seçici filtrenin FRET isimasi harici dalga boylarini sogurmasi, - söz konusu biyosensör cihazinin dinamik ölçüm gerçeklestirmek amaciyla FRET sinyallerinin zamanla degisiminin takibini yapmasi islemleri vasitasiyla patojenlerin varliginin tespit edilmesini saglamasi islemleri gerçeklestirilmektedir. The invention, including a biosensor device that allows the detection of pathogens; a display, with a laser diode, that allows the operation result to be reported on the biosensor device a paired optical fiber, the laser light emanating from an optical fiber is connected to a pathogen detection chip. A wavelength-selective mirror that directs A designed pathogen detection chip focuses laser light emanating from an optical fiber onto the top surface of the sample. A lens is a device that allows laser light emanating from an optical fiber to be converted into a plane wave. collimation system, a PMT sensor surface (70) used to detect light, name FRET A selective filter (71) that allows wavelengths other than through the components of a tub body to which it is mounted and a tub cover for a tub body; - a specially designed device to convert laser light emanating from an optical fiber into a plane wave. use of collimation system, - a wavelength to direct laser light from an optical fiber to a pathogen detection chip use of selective mirror, - a chip of laser light emanating from the optical fiber of the lens located in front of the said pathogen detection chip focusing on the surface - the illumination of some of the fluorescent light generated in the pathogen detection chip, emanating from the optical fiber pass through the path of the light and collect in the lens, - the wavelength of the fluorescent light is not reflected in the selective mirror, but passes through the PMT sensor reaching the surface, - The selective filter before the PMT sensor surface absorbs wavelengths other than the FRET name, - the biosensor device in question to perform dynamic measurement of FRET signals Detection of the presence of pathogens through the processes of following the change over time. to ensure that transactions are carried out.
Bulus, patojenlerin tespit edilmesine imkân veren bir biyosensör cihazina iliskin bir patojen tespit yöntemi olmak üzere; - bahsedilen patojen tespit çipinin biyosensör cihazina yerlestirilmesi, - teknik nedenlerle olusabilecek hatalarin önlenmesi amaciyla biyosensör cihazinin kalibrasyon islemi yapmasi, - biyosensör cihazina iliskin optik fiberden çikan lazer isigin açilarak veri alinmasi ve söz konusu verilerin ortalamasinin alinmasi, - bir hastadan alinan örnegin bahsedilen patojen tespit çipine yerlestirilerek teste baslanmasi, - biyosensör cihazina iliskin optik fiberden çikan lazer isigin açilmasi ve patojen tespit çipinden verilerin toplanmaya baslanmasi, - bahsedilen patojen tespit çipinden toplanan verilerin hastadan alinan örnegin patojen tespit çipine yerlestirilmeden önceki ortalama verilerle karsilastirilmasi - eger olusan FRET isimasi artisi belirli bir deger üzerindeyse sonucun pozitif çikmasi, - eger olusan FRET isimasi artisi belirli bir degerin altindaysa sonucun negatif olarak çikmasi Sekillerin Kisa Açiklamasi Sekil 1'de bulus konusu biyosensör cihazinin sekil la. sekil 1b, sekil 1c ve sekil 1d'deki farkli açidan görünümleri ve optik sistem bilesenleri gösterilmektedir. The invention relates to a pathogen detection device for a biosensor device that allows the detection of pathogens. including the method; - insertion of said pathogen detection chip into the biosensor device, - in order to prevent errors that may occur due to technical reasons, the biosensor device performing the calibration process, - receiving data by turning on the laser light coming out of the optical fiber of the biosensor device and speaking taking the average of the data in question, - starting the test by placing a sample taken from a patient on the said pathogen detection chip, - turning on the laser light emanating from the optical fiber of the biosensor device and from the pathogen detection chip data collection, - pathogen detection, for example, from the patient of the data collected from the said pathogen detection chip compared to the average data before it was inserted into the chip. - If the FRET name increase is above a certain value, the result is positive, - if the FRET name increment is below a certain value, the result will be negative Brief Description of Figures In Figure 1, the inventive biosensor device is shown in figure la. from different angle in figure 1b, figure 1c and figure 1d views and optical system components are shown.
Sekil 2'de bulus konusu biyosensör cihazina iliskin optik sistem bilesenleri gösterilmektedir. In Figure 2, optical system components of the inventive biosensor device are shown.
Sekil 3'te bulus konusu biyosensör cihazina iliskin optik sistemin yansitmali olarak çalisma versiyonu gösterilmektedir Sekil 4'te bulus konusu biyosensör cihazina iliskin optik sistemin alternatif bir konfigürasyonu gösterilmektedir. In Figure 3, the reflective working version of the optical system of the inventive biosensor device is shown An alternative configuration of the optical system of the inventive biosensor device is shown in Figure 4 is shown.
Sekil 5'te bulus konusu biyosensör cihazina iliskin patojen tespit yöntemi akis semasi gösterilmektedir. In Figure 5, pathogen detection method flowchart related to the inventive biosensor device is shown.
Sekil 6”da bulus konusu patojen tespit yöntemine iliskin elde edilen sonucun kontrol edilmesiyle ilgili bir akis semasi gösterilmektedir. Figure 6. A flow chart is shown.
Referans Numaralari . Biyosensör Cihazi 11. Ekran . Optik Fiber . Dikroik ayna 31. Ikinci dikroik Ayna 40. Patojen Tespit Çipi 41. Fonksiyonel Yüzey 50. Mercek 60. Kolimasyon Sistemi 70. PMT Sensör Yüzeyi 71. Seçici Filtre 80. Fotodedektör 90.Küvet Gövdesi 91. Küvet Kapagi 100. Patojen tespit kitinin biyosensör cihazina yerlestirilmesi 105. Biyosensör cihazinin kalibrasyon islemi yapmasi ve kalibrasyon islemini yaptiktan sonra cihazin bu degeri baslangiç degeri olarak belirlemesi 110. Biyosensör cihazina iliskin optik fiberden çikan lazer isigin açilarak veri alinmasi ve söz konusu verilerin ortalamasinin alinmasi 115. Hastadan alinan örnegin patojen tespit çipine yerlestirilmesi ve teste baslanmasi 120. Lazer isigin 5., 10. ve 20. saniyelerde 1 saniye süre ile açilmasiyla veriler toplanmasi 125. Toplanan verilerin patojen tespit çipine örnek yerlestirilmeden önceki veriler ile karsilastirilmasi 130. Eger olusan FRET isimasi artisi belirli bir deger üzerindeyse sonucun pozitif çikmasi 135. Eger olusan FRET isimasi artisi belirli bir degerin altindaysa sonucun negatif olarak çikmasi çikan lazer isigin açilmasindan itibaren birinci asamada alinan deger baslangiç degerine göre önceden belirlenmis belli bir deger araligindaki artisa karsilik geliyor ise sonucun ekranda pozitif olarak gösterilmesi, 205. biyosensör cihazi tarafindan elde edilen pozitif sonucun teyit edilmesi için ikinci asamada biyosensör cihazi (10) tarafindan tekrar veri alinmasi, 210. FRET isimasi artisi ikinci asamada sabit olarak kalir veya düserse sonucun ekranda pozitif olarak gösterilmesi 215. Biyosensör cihazinda belirlenen süreler içerisinde toplanan verilerin bir önceki veriler ile karsilastirilmasi 220. Biyosensör cihazi (10) tarafindan elde edilen verilerde birinci asamadan itibaren FRET isimasi artisi devam ederse biyosensör cihazinin 1 dakika boyunca tekrarlayan sürelerde her 10 saniyede bir veri almaya devam etmesi ve artis sabitlenmezse biyosensör cihazi ekrani vasitasiyla testin tekrarlanmasinin istenmesi 225. Ilk 1 dakika içerisindeki herhangi bir zaman diliminde FRET isimasi artisi esik degerin üzerine çikarsa sonucun ekranda pozitif olarak gösterilmesi 230. FRET isimasi artisinin birinci asamada esik degere yakin degerle arasinda kalmasi durumunda olusabilecek hatayi önlemek üzere biyosensör cihazinin 1 dakika boyunca tekrarlayan sürelerle veri toplamasi 235.1 dakika sonunda FRET isimasi artisi esik degerin altinda kalirsa biyosensör cihazi ekrani vasitasiyla testin tekrarlanmasinin istenmesi 240. Birinci asamada FRET isimasi azalmasi gerçeklesmesi halinde sonucun ekranda negatif olarak gösterilmesi 245. Biyosensör cihazinin yanlis pozitif sonuçlari önlemek üzere kritik deger ve üzerindeki FRET isimasi artisi oldugu taktirde ekranda vasitasiyla örnegin tekrar alinmasini istemesi Bulusun Detayli Açiklamasi Mevcut bulus, FRET teknigi için özellestirilmis optik temelli olarak patojenlerin tespit edilmesine imkân veren bir biyosensör cihazi (10) ile ilgilidir. Bulus, bir biyosensör cihazina (10) özel olarak gelistirilen farkli dalga boylarinda enerjiye sahip floresan moleküllerin ayni hedefte bir araya gelmesini saglayan ve iki molekül arasinda meydana gelen FRET olayi sonucunda açiga çikan emisyon optik güç degerlerindeki degisime bakilarak mikrobiyolojik yapinin kesin varligi hakkinda hükme varilmasina olanak veren tek kullanimlik bir patojen tespit çipi (40) üzerinden dinamik olarak FRET sinyali alinmasi sayesinde patojenlerin kisa bir süre içerisinde tespit edilmesini saglayan bir yöntemle ilgilidir. Reference Numbers . Biosensor Device 11. Display . Optical Fiber . dichroic mirror 31. Second dichroic Mirror 40. Pathogen Detection Chip 41. Functional Surface 50. Lens 60. Collimation System 70. PMT Sensor Surface 71. Selective Filter 80. Photodetector 90. Tub Body 91. Tub Cover 100. Placing the pathogen detection kit into the biosensor device 105. After the calibration process of the biosensor device and the calibration process, the device set this value as the initial value 110. Receiving data by turning on the laser light coming out of the optical fiber of the biosensor device and averaging the data 115. Placing the sample taken from the patient on the pathogen detection chip and starting the test 120. Data collection by turning on the laser light for 1 second at the 5th, 10th and 20th seconds 125. Comparison of collected data with data before sample insertion into the pathogen detection chip 130. If the resulting FRET name increase is above a certain value, the result is positive 135. If the resulting FRET name increment is below a certain value, the result will be negative emitted laser light The value taken in the first step since the opening is predetermined according to the initial value. If it corresponds to an increase in a certain value range, the result will be shown as positive on the screen, 205. in the second step to confirm the positive result obtained by the biosensor device retrieving data by the biosensor device (10), 210. If the FRET name increment remains constant or drops in the second phase, the result will be positive on the screen. display as 215. The data collected in the biosensor device within the specified periods are compared with the previous data. comparison 220. FRET name from the first stage in the data obtained by the biosensor device (10) If the increase continues, the biosensor device will be reset every 10 seconds for 1 minute for repetitive periods. If it continues to receive a data and the increase is not stable, test via the biosensor device screen. request to repeat 225. The FRET name increase over the threshold value at any time during the first 1 minute If it is, the result will be shown as positive on the screen. 230. If the FRET name increase is between the value close to the threshold value in the first stage In order to prevent any error that may occur, the data of the biosensor device is repeated for 1 minute. collection If the FRET name increase remains below the threshold value after 235.1 minutes, the biosensor device screen requesting a repeat of the test 240. If the FRET name decrease occurs in the first stage, the result will be displayed as negative. display 245. FRET of the biosensor device at and above critical value to prevent false positive results Requesting the sample to be taken again via the screen in case of an increase in the name Detailed Description of the Invention The present invention focuses on the detection of pathogens based on optics specialized for the FRET technique. It relates to a biosensor device (10) that allows The invention specifically relates to a biosensor device (10). Developed fluorescent molecules with different wavelengths of energy are brought together on the same target. It is released as a result of the FRET event that occurs between two molecules. about the exact existence of the microbiological structure by looking at the change in the emission optical power values. dynamically via a disposable pathogen detection chip (40) that allows judgment Thanks to receiving the FRET signal, it is a method that enables the detection of pathogens in a short time. relates to the method.
Bir hastadan alinan örnek, özel bir solüsyonla karistirildiktan sonra patojen tespit çipi (40) üzerine yerlestirilerek biyosensör Cihazi (10) tarafindan ortamda patojen varsa FRET sinyali alinarak tespit edilmesi saglanmaktadir. Patojen tespit çipinde (40) ultraviyole gibi belirli bir dalga boyunda isik ile uyarilip mavi isima yapan bir birincil prob baglidir. Bahsedilen solüsyon ise, mavi renklerde uyarilabilen ve FRET isimasi dalga boyu yesil renkte olan bir ikincil prob ihtiva etmektedir. Bahsedilen birincil problar ve ikincil problar patojeni tanimaya yönelik seçilmis olan antikor/proteinler veya patojen nükleik asitlerinin eslenigi olarak tasarlanip üretilmis olan nükleik asitlerdir (DNA/RNA oligomerleri veya aptamerler). Sistemde herhangi bir FRET çifti, FRET dönürü çipe bagli ve alicisi (acceptor) solüsyonda veya tam tersi sekilde de kullanilabilmektedir. A sample from a patient is placed on the pathogen detection chip (40) after mixing with a special solution. If there is a pathogen in the environment, it can be detected by receiving the FRET signal by the biosensor device (10). is provided. With light of a certain wavelength, such as ultraviolet, in the pathogen detection chip (40) A primary probe that is excited and glows blue is connected. Said solution is blue in color. It contains an excitable secondary probe named FRET, whose wavelength is green. Said primary probes and secondary probes are antibodies/proteins selected for pathogen recognition or are nucleic acids (DNA/RNA) that have been designed and produced as conjugates of pathogen nucleic acids. oligomers or aptamers). Any FRET pair in the system, the FRET loop is connected to the chip and its receiver (acceptor) can be used in solution or vice versa.
Bulus konusu biyosensör cihazinin (10) farkli açidan görünümleri ve optik sistem bilesenleri sekil 1'de görülmektedir. Sistemde de görüldügü gibi; biyosensör cihazina (10) iliskin islem sonucunun bildirilmesine imkan veren bir ekran (11), bir lazer diyot ile eslestirilmis bir optik fiber (20), bir optik fiberden (20) çikan isigin bir patojen tespit çipine (40) yönlendirilmesini saglayan bir dalga boyu seçici dikroik ayna (30), bir biyosensör cihazi (10) için özel olarak tasarlanmis bir patojen tespit çipi (40), optik fiberden (20) çikan isigi örnegin üst yüzeyine odaklayan bir mercek (50), optik fiberden (20) çikan isigin düzlem dalga haline getirilmesine imkan veren bir kolimasyon sistemi (60), isigin tespit edilmesinde kullanilan bir PMT sensör yüzeyi (70), FRET isimasi haricindeki dalga boylarinin sogurulmasina imkan veren bir seçici filtre (71), bir patojen tespit çipinin (40) monte edildigi bir küvet gövdesi (90) ve bir küvet gövdesine (90) iliskin bir küvet kapagi (91) bilesenlerini ihtiva etmektedir. Views of the inventive biosensor device (10) from different angles and optical system components are shown in the figure. It is seen in 1. As seen in the system; the operation result of the biosensor device (10) an optical fiber (20) paired with a laser diode, an optical a wavelength selector that directs the light from the fiber 20 to a pathogen detection chip 40 dichroic mirror (30), a pathogen detection chip (40) specially designed for a biosensor device (10), a lens (50) that focuses the light emanating from the optical fiber (20) to the upper surface of the sample, from the optical fiber (20) A collimation system (60) that allows the emitted light to become a plane wave, A PMT sensor surface (70) used to detect wavelengths other than the FRET name a selective filter (71) that allows the body (90) and a tub cover (91) for a tub body (90).
Patojen tespit çipi (40) bir küvet gövdesinin (90) tabanina monte edilmis durumdadir. Küvet gövdesi (90) tercihen silindirik formdadir ve üst tarafinda bir test çubugunun girebilecegi bir delige haiz bir küvet kapagi (91) içermektedir. The pathogen detection chip 40 is mounted on the bottom of a cuvette body 90. tub body (90) is preferably cylindrical in form and has a hole at the top into which a test stick can be inserted. the tub cover (91).
Bulus konusu biyosensör cihazina (10) iliskin optik sistem bilesenleri Sekil 2'de gösterilmektedir. The optical system components of the inventive biosensor device (10) are shown in Figure 2.
Mevcut bulusta biyosensör cihazina (10) iliskin bir optik fiberden (20) çikan lazer isik özel tasarim bir kolimasyon sistemi (60) kullanilarak düzlem dalga haline getirilmektedir. Bunun akabinde, dalga boyu seçici dikroik ayna (30) kullanilarak lazer isik bir patojen tespit çipine (40) yönlendirilmektedir. Söz konusu dalga boyu seçici dikroik ayna (30) bir dikroik aynadir ve 450 nm altindaki degerleri yansitmaktadir. Patojen tespit çipinin (40) önünde bulunan mercek (50), isigi örnegin üst yüzeyine odaklamaktadir. Genel olarak, isik önce düz dalga haline getirilerek sonrasinda hedef nokta üzerine odaklanmaktadir. Hastadan alinan örnek, optik fiber (20) vasitasiyla lazer isik ile aydinlatildiktan sonra aydinlatma alani çevresinde olusacak hacimde, daha uzun dalga boylu ve her yöne esit dogrultuda bir floresan isimasi modellenmistir. Söz konusu floresan isigin bir kismi aydinlatma isiginin yolundan ve mercekte (50) toplanacak sekilde geçmektedir. Patojen tespit çipinin (40) üst kisminda bulunan bir fonksiyonel yüzey (41) sayesinde isik, dalga boyu seçici dikroik aynada (30) yansimayip içinden geçerek patojen tespit çipinin (40) içinden geçerek PMT sensör yüzeyine (70) ulasmaktadir. Seçici filtre (71), FRET isimasi harici dalga boylarini sogurmaktadir. Bulus konusu biyosensör cihazi (10) uyarilma isigi isima tespit sistemlerini bir arada kullanmaktadir. Bulus konusu yöntemde uyarilma isigi ve isima için lazer isik ve floresan tercih edilmistir. Söz konusu biyosensör cihazi (10) FRET sinyallerinin zamanla degisiminin takibini yaparak dinamik ölçüm yapmaktadir. In the present invention, laser light emanating from an optical fiber (20) related to the biosensor device (10) is a special design. It is turned into a plane wave using the collimation system (60). After that, the wavelength laser light is directed to a pathogen detection chip (40) using the selective dichroic mirror (30). Promise The subject wavelength selective dichroic mirror (30) is a dichroic mirror and its values below 450 nm reflects. The lens (50) located in front of the pathogen detection chip (40) directs the light to the upper surface of the sample. focuses. In general, the light is first turned into a straight wave and then onto the target point. focuses. After the sample taken from the patient is illuminated with laser light through the optical fiber (20) Then, in the volume to be formed around the lighting area, longer wavelength and equal in all directions. A fluorescent name is modeled in the direction. Part of the fluorescent light in question is illuminating. It passes through the path of the light and to be collected in the lens (50). The top of the pathogen detection chip (40) Thanks to a functional surface (41) on the part of the light, the light is in the wavelength selective dichroic mirror (30). not reflected but passing through the pathogen detection chip (40) to the PMT sensor surface (70). is reaching. The selective filter 71 absorbs wavelengths other than the FRET name. subject of the invention biosensor device (10) uses excitation light radiation detection systems together. subject of the invention In this method, laser light and fluorescence are preferred for excitation light and radiation. The biosensor in question device (10) performs dynamic measurements by following the change of FRET signals over time.
Patojen tespit çipi (40), mavi isima yapan bir birincil probun dalga boyuna göre uyarilmaktadir. Bu sebeple ortamda patojen yokken, patojen tespit çipi (40) üzerindeki birincil probdan mavi floresan isima gelirken, ortamda patojen olmasi durumunda aralarindaki enerji transferinden dolayi yesil floresan isima görülmektedir. Enerji transferinin yalnizca ortamda patojen varken gerçeklesmesi sebebiyle hassas bir sekilde patojenin varligi ölçülebilmektedir. Tani koyma islemi ise bir dakikanin altinda sürmektedir. The pathogen detection chip 40 is excited at the wavelength of a primary probe that glows blue. This Therefore, when there is no pathogen in the environment, blue fluorescence from the primary probe on the pathogen detection chip (40) When it comes to heat, in case of pathogen in the environment, it is green due to the energy transfer between them. fluorescent name appears. Energy transfer occurs only when there is a pathogen in the environment Therefore, the presence of the pathogen can be measured sensitively. Diagnosis is less than a minute. continues under.
Sekil 3'te bulus konusu biyosensör cihazina iliskin optik sistemin yansitmali olarak çalisma versiyonu gösterilmektedir. Patojen tespit çipinin (40) alt kisminda bulunan birfonksiyonel yüzey (41) sayesinde isik, dalga boyu seçici dikroik aynada (30) yansima yaparak patojen tespit çipinin (40) içinden geçmeyip PMT sensör yüzeyine (70) ulasmaktadir. Biyosensör cihazi (10) ile hem geçirmeli (transmission) hem de yansitmali (reflection) modda ölçüm yapilabilmektedir. In Figure 3, the reflective working version of the optical system of the inventive biosensor device is shown. Thanks to a functional surface (41) located at the bottom of the pathogen detection chip (40) The light is reflected through the pathogen detection chip (40) by reflecting in the wavelength selective dichroic mirror (30). it does not pass and reaches the PMT sensor surface (70). Both pass-through with biosensor device (10) Measurements can be made in both (transmission) and reflective (reflection) modes.
Bulus konusu biyosensör cihazina iliskin optik sistemin alternatif bir konfigürasyonu sekil 4'te gösterilmektedir. Burada, Seçici filtre (71) yerine farkli bir dalga boyu seçici ikinci dikroik ayna (31) bulunmaktadir. Söz konusu dalga boyu seçici ikinci dikroik ayna (31) ultraviyole ile uyarilip mavi isima yapan bir birincil probun bagli oldugu patojen tespit çipi (40) üzerinden gelen FRET sonucu olmayan floresan isimayi baska bir fotodedektöre (80) iletmektedir. FRET isimasini ise geçirmektedir. Bu sayede floresan/FRET isimasi arasinda oransal ölçüm yapilarak biyosensör cihazinin (10) hassasiyeti arttirilmaktadir. An alternative configuration of the optical system of the inventive biosensor device is shown in Figure 4. is shown. Here, instead of the Selective filter (71), a different wavelength selective second dichroic mirror (31) are available. The said wavelength selective second dichroic mirror (31) is excited by ultraviolet and turns blue. non-FRET result from the pathogen detection chip (40) to which a primary probe is attached transmits the fluorescent light to another photodetector (80). It goes by the name FRET. This In this way, the proportional measurement between the fluorescence/FRET name is made and the biosensor device (10) sensitivity is increased.
Biyosensör cihazi (10), patojenlerin floresan molekülleri ile etkilesmesinden sonra olusan FRET sinyalini elektrik sinyallerine dönüstürülmesi saglamaktadir. Floresan moleküller isiga hassas olan moleküllerdir ve uzun süre lazer isigina maruz birakildiklarinda isima özelliklerini yitirerek negatif sonuç verebilmektedirler. Biyosensör cihazi (10) içerisine yerlestirilen PMT sensör yüzeyi (70) her gelen emisyon isigini içerisinde bulunan seçici filtre (71) sayesinde akima dönüstürmektedir. PMT gücü degistirilerek akima dönüstürülen miktar arttirilmaktadir. Bu gücün arttirilmasi, olusabilecek arka plan gürültüyü de arttirmakta ve olusacak sinyal degisimleri gürültü içinde kaybolmaktadir. Bu sebeple biyosensör cihazin (10) her patojen tespit kiti yerlestirildiginde kalibrasyon yapmasi gerekmektedir. The biosensor device (10) is FRET, which is formed after pathogens interact with fluorescent molecules. It converts the signal to electrical signals. Fluorescent molecules are light sensitive They are molecules and when exposed to laser light for a long time, they lose their heating properties and become negative. they can produce results. The PMT sensor surface (70) placed inside the biosensor device (10) It converts the incoming emission light into current thanks to the selective filter (71) in it. PMT By changing the power, the amount converted to current is increased. Increasing this power, it also increases the background noise and the signal changes that will occur are lost in the noise. This For this reason, the biosensor device (10) must calibrate each time a pathogen detection kit is placed. required.
Bulus konusu biyosensör cihazina (10) iliskin patojen tespit yöntemi akis semasi sekil 5'te gösterilmektedir. Öncelikle patojen tespit çipinin biyosensör cihazina yerlestirilmesi (100) saglanmaktadir. Sonrasinda ise biyosensör cihazi kalibrasyon islemi yapmaktadir ve kalibrasyon islemini yaptiktan sonra cihaz bu degeri baslangiç degeri olarak belirlemektedir (105). Biyosensör cihazi (10) teknik nedenler ile olusabilecek hatalari önlemek için her bir patojen tespit kiti (40) yerlestirildiginde kalibrasyon yapmaktadir. Söz konusu kalibrasyon isleminde her bir patojen tespit çipi (40) için önceden belirlenmis olan lazer isiga karsilik gelen güç ayarlanmakta ve her ölçümde gürültü en düsük seviyede tutulurken floresan moleküllerinin uyarilabilecegi sabit bir degere getirilmesi saglanmaktadir. Ek olarak, biyosensör cihazina optik fiberden çikan lazer isigin açilarak veri alinmasi ve söz konusu verilerin ortalamasinin alinmasi saglanmaktadir (110). Biyosensör cihazi (10) floresan moleküllerin zarar görmesini engellemek için, her seferinde 1 saniye süre ile optik fiberden (20) gelen lazer isigi açarak saniyede 2000 tane veri toplamaktadirBiyosensör cihazinin (10) toplandigi degerlerin bir ortalamasi alinarak söz konusu deger sistem hafizasina yazildiktan sonra, biyosensör cihazina (10) iliskin bir ekran (11) vasitasiyla ölçüm yapacak olan kisiden hastadan alinan örnegin yerlestirilmesi ve teste baslamasi istenmektedir. Bunun akabinde hastadan alinan örnek patojen tespit çipine yerlestirilerek teste baslanmaktadir (115). Bir hastadan alinan örnek, patojen tespit çipine (40) yerlestirilmeden önce mavi renklerde uyarilabilen ve FRET isimasi dalga boyu yesil renkte olan bir ikincil prob içeren solüsyon ile etkilesime girmektedir. Sonrasinda ise, söz konusu patojen ve ikincil prob içerigi patojen tespit çipinin (40) üzerine yerlestirilmektedir. Bu sayede, patojen tespit çipi (40) üzerinde bagli olan birincil prob ile hastadan alinan örnegin serbest olarak birlestirildigi ikincil prob içerisindeki floresan madde bir araya gelmektedir. Birincil ve ikincil problar ortamda bulunan ayni patojen üzerine baglanmaktadirlar. Bahsedilen birincil ve ikincil problar farkli dalga boylarinda ve farkli renklerde iki probu ifade etmektedir. Dolayisiyla mavi ve yesil renklerle kisitli olmamakla birlikte patojen tespit çipi (40) ve hastadan alinan örnegin etkilesime girdigi probun farkli renklerde isima yapmasi gerektigi belirtilmistir. Bu islemin akabinde optik fiberden (20) çikan lazer isigin belirli asamalarda 1 saniye süre ile açilmasiyla veriler toplanmaya baslanmaktadir (120). The pathogen detection method flowchart of the inventive biosensor device (10) is shown in Figure 5. is shown. First, placing the pathogen detection chip on the biosensor device (100) is provided. Afterwards, the biosensor device performs the calibration process and the calibration After performing the operation, the device determines this value as the initial value (105). biosensor device (10) each pathogen detection kit (40) to prevent errors that may occur due to technical reasons. It calibrates when placed. In the calibration process, each pathogen is detected. The power corresponding to the laser light predetermined for the chip (40) is adjusted and at each measurement a constant value at which fluorescent molecules can be excited while keeping noise to a minimum. is provided to be brought. In addition, the laser light emanating from the optical fiber is turned on to the biosensor device. data is obtained and the average of the data in question is taken (110). biosensor optical device (10) for 1 second at a time to prevent damage to the fluorescent molecules. It turns on the laser light coming from the fiber (20) and collects 2000 data per second. (10) by taking an average of the values from which it was collected, after the said value is written to the system then, from the person who will make the measurement via a screen (11) related to the biosensor device (10) from the patient. It is requested that the sample taken is placed and the test starts. Subsequently, the patient The test is started by placing the sample on the pathogen detection chip (115). Sample taken from a patient, Before it is placed on the pathogen detection chip (40), a waveform that can be excited in blue colors and called FRET interacts with the solution containing a green-sized secondary probe. Afterwards, the word The subject pathogen and secondary probe content are placed on the pathogen detection chip (40). In this way, With the primary probe connected on the pathogen detection chip (40), the sample taken from the patient is freely The fluorescent substance in the secondary probe to which it is attached comes together. Primary and secondary probes They bind to the same pathogen in the environment. The primary and secondary probes mentioned are different. It refers to two probes of different wavelengths and different colors. So in blue and green colors Although not limited, the pathogen detection chip (40) and the probe with which the sample taken from the patient interacts. It has been stated that it needs to be heated in different colors. After this process, the output from the optical fiber (20) data is started to be collected when the laser light is turned on for 1 second at certain stages (120).
Toplanan veriler hastadan alinan örnek patojen tespit çipine yerlestirilmeden önceki ortalama veriler ile karsilastirilmaktadir (125). Söz konusu birincil ve ikincil problarin farkli dalga boylarinda uyarilarak isaretlenmis olmalarindan dolayi bir araya getirildiklerinde aralarindaki enerji farki sebebiyle olusan ve FRET olarak adlandirilan enerji transferi gerçeklesmektedir. Hastadan alinan örnek ve bir ikincil probun FRET çipi üzerine yerlestirilmesiyle alinan FRET sinyallerin zamanla degisimi ise biyosensör cihazi (10) ile takip edilerek patojenlerin varligina iliskin tani konulmaktadir. Eger olusan FRET isimasi artisi belirli bir deger üzerindeyse sonucun pozitif çiktigi (130), eger olusan FRET isimasi artisi belirli bir degerin altindaysa sonucun negatif olarak çikmasi kabul edilmektedir (135). The collected data is the average data from the patient before the sample is placed on the pathogen detection chip. compared with (125). Excitation of said primary and secondary probes at different wavelengths Due to the fact that they are marked, when they are brought together, they occur due to the energy difference between them. and energy transfer called FRET takes place. Sample from the patient and a secondary The time change of the FRET signals received by placing the probe on the FRET chip is the biosensor. The diagnosis is made regarding the presence of pathogens by monitoring with the device (10). If FRET occurs If the name increase is above a certain value, the result is positive (130), if the resulting FRET name If the increase is below a certain value, it is accepted that the result is negative (135).
Bulus konusu patojen tespit yöntemine iliskin elde edilen sonucun kontrol edilmesiyle ilgili bir akis semasi Sekil 6`de gösterilmektedir. Biyosensör cihazinda (10) tespit edilen FRET isimasi artisinin optik fiberden (20) çikan lazer isigin açilmasindan itibaren birinci asamada alinan deger baslangiç degerine (105) göre önceden belirlenmis belirli bir deger araligindaki artisa karsilik geliyor ise sonucun ekranda (11) pozitif olarak gösterilmesi (200) saglanmaktadir. Bu artis, pozitif sonuçlar için birinci asamaya ayrilan süre içerisinde olusmaktadir. Ancak, biyosensör cihazi tarafindan elde edilen pozitif sonucun teyit edilmesi için ikinci asamada biyosensör cihazi (10) tarafindan tekrar veri alinmaktadir (205). Eger artis ikinci asamada sabit olarak kalir veya düserse biyosensör cihazina (10) iliskin ekranda (11) sonuç pozitif olarak gösterilmektedir (210). Biyosensör cihazi belirlenen her süre içerisinde topladigi verileri bir önceki veriler ile kiyaslamaktadir (215). Alinan verilerde birinci asamadan itibaren floresan sinyal artisi (FRET isimasi artisi) devam ederse biyosensör cihazi 1 dakika boyunca tekrarlayan sürelerde veri almaya devam etmektedir ve sabitlenmezse biyosensör cihazina iliskin ekran vasitasiyla testin tekrarlanmasinin istenmektedir (220). Ekran (11) üzerinde sonuç belirlenemedi testi tekrarlayin seklinde bir yazi gösterilmektedir. Ilk 1 dakika içerisindeki herhangi zaman diliminde artis esik degerinin üzerine çiktigi durumda ise sonuç ekranda pozitif olarak gösterilmektedir (225). Artis birinci asamada esik degere yakin bir deger arasinda kalmasi durumunda olusabilecek hatayi önlemek üzere biyosensör cihazi 1 dakika boyunca her tekrarlayan sürelerle veri toplamaktadir (230). 1 dakika sonunda FRET isimasi artisi esik degerin altinda kalirsa biyosensör cihazi ekrani vasitasiyla testin tekrarlanmasinin istenmektedir (235). Test sonucu belirlenemedi seklinde bir uyarinin biyosensör cihazina (10) iliskin ekranda (11) gösterilmesi saglanarak, örnegin hastadan tekrar alinip testin tekrarlanmasi istenmektedir. Hatali sonuçlar, genel olarak örnegin dogru olarak alinamadigi zamanlarda ortaya çikmaktadir. Ancak negatif sonuçlarda genellikle floresan miktarinda azalma gözlenmektedir. Birinci asamada floresan azalmasi gerçeklesmesi halinde sonuç biyosensör cihazina (10) iliskin ekranda (11) negatif olarak gösterilmektedir (240). Olusan sinyallerin kritik degerin üzerinde olmasi floresan proteinlerin kontaminasyon sonucu baska molekül veya maddeler (yanak ve agiz mukozasinda istenmeyen artiklarin varligi veya uygun olmayan eküvyon çubuklari ile örnegin alinmasi durumunda ortaya çikan maddeler) ile etkilesmesi sonucu nedeniyle olusabilmektedir. Biyosensör cihazinin yanlis pozitif sonuçlari önlemek üzere kritik deger ve üzerindeki FRET isimasi artisi oldugu taktirde ekranda vasitasiyla örnegin tekrar alinmasini istemektedir (245).A flow for checking the result obtained regarding the pathogen detection method of the invention The diagram is shown in Figure 6. The increase in FRET nomenclature detected in the biosensor device (10) The value taken in the first step after the laser light coming out of the optical fiber (20) is turned on is the initial value. corresponds to an increase in a predetermined value range according to the value (105) it is provided (200) that the result is displayed as positive on the screen (11). This increase is for positive results. occurs within the time allotted to the first stage. However, the results obtained by the biosensor device To confirm the positive result, the data is repeated by the biosensor device (10) in the second step. are taken (205). If the increase remains stable or falls in the second stage, it is returned to the biosensor device. On the screen (11) for (10), the result is shown as positive (210). Each biosensor device determined compares the data collected over time with the previous data (215). The first in the received data If fluorescent signal increase (FRET name increase) continues from step 1, biosensor device 1 continues to receive data at repetitive times for minutes and if not fixed, the biosensor It is requested to repeat the test via the screen of the device (220). On screen (11) no result determined repeat test is displayed. within the first 1 minute If the increase exceeds the threshold value in any time period, the result is positive on the screen. is shown as (225). The increase remains between a value close to the threshold value in the first stage. In order to prevent the error that may occur in the case of collects data over time (230). If the FRET name increase remains below the threshold value after 1 minute it is requested to repeat the test via the biosensor device screen (235). test result Displaying a warning on the screen (11) related to the biosensor device (10) stating that it could not be detected For example, the patient is asked to take the test again and repeat the test. Incorrect results, general It occurs when the sample cannot be taken correctly. However, in negative results Generally, a decrease in the amount of fluorescence is observed. Fluorescence reduction in the first stage if it happens, the result will be negative on the screen (11) of the biosensor device (10). is shown (240). If the resulting signals are above the critical value, fluorescent proteins other molecules or substances as a result of contamination (undesirable in the cheek and mouth mucosa) the presence of residues or sample collection with unsuitable swab sticks. may occur as a result of interaction with substances). False positive of the biosensor device If there is an increase in the critical value and the FRET name above it, in order to prevent the results, it will appear on the screen. He wants the sample to be taken again via (245).
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| PCT/TR2020/051424 WO2022139707A1 (en) | 2020-12-26 | 2020-12-28 | A specialized biosensor device and pathogen detection method for fret technique |
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