TR201910569A2 - DESIGN AND PRODUCTION OF PARTIAL GRAVITY PLATFORM USING MAGNETIC FORCES FOR CELLULAR APPLICATIONS - Google Patents

DESIGN AND PRODUCTION OF PARTIAL GRAVITY PLATFORM USING MAGNETIC FORCES FOR CELLULAR APPLICATIONS Download PDF

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TR201910569A2
TR201910569A2 TR2019/10569A TR201910569A TR201910569A2 TR 201910569 A2 TR201910569 A2 TR 201910569A2 TR 2019/10569 A TR2019/10569 A TR 2019/10569A TR 201910569 A TR201910569 A TR 201910569A TR 201910569 A2 TR201910569 A2 TR 201910569A2
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cell culture
cells
platform
magnetic
culture platform
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Yilmaz Esra
Anil İnevi̇ Müge
Meşe Özçi̇vi̇ci̇ Güli̇stan
Cumhur Teki̇n Hüseyi̇n
Özçi̇vi̇ci̇ Engi̇n
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Izmir Yueksek Teknoloji Enstituesue
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Priority to PCT/TR2020/050536 priority patent/WO2021010917A1/en
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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M35/00Means for application of stress for stimulating the growth of microorganisms or the generation of fermentation or metabolic products; Means for electroporation or cell fusion
    • C12M35/06Magnetic means
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/02Form or structure of the vessel
    • C12M23/12Well or multiwell plates

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Abstract

Buluş, uzay biyolojisi alanında bilgi üretmek amacıyla manyetik prensiplerden yararlanarak tasarlanmış canlı hücrelerin üzerindeki ağırlık kuvvetlerini azaltarak, farklı gezegen ve uydulardaki kütle çekimine maruz kalan hücrelerin morfolojik ve fonksiyonel adaptasyonlarını test edebilecek bir hücre kültürü platformu ile ilgilidir.The invention relates to a cell culture platform that can test the morphological and functional adaptations of cells subjected to gravity in different planets and satellites by reducing the weight forces on living cells designed using magnetic principles to generate information in the field of space biology.

Description

TARIFNAME HÜCRESEL UYGULAMALAR IÇIN MANYETIK KUWETLERI KULLANAN KISMI YERÇEKIMI PLATFORMU TASARIM VE ÜRETIMI Bulusun Ilgili Oldugu Teknik Alan Bulus, uzay biyolojisi alanIa bilgi üretmek amaclsîla manyetik prensipler kullanüârak tasarlanmlgl hücre kültürüne olanak saglayan biyoteknolojik bir platform ile ilgilidir. DESCRIPTION THE PART USING MAGNETIC FORCES FOR CELL APPLICATIONS GRAVITY PLATFORM DESIGN AND MANUFACTURING Technical Field of the Invention The invention is carried out using magnetic principles to generate knowledge for the field of space biology. It is about a biotechnological platform that enables engineered cell culture.

Bulusla Ilgili Teknigin Bilinen Durumu (Önceki Teknik) Mekanik kuwetler canlüdokularia saglllZllZlform ve fonksiyonun olusmasIa rol oynayan temel parametrelerin arasIia yer almaktadIEve bu mekanik kuvvetlerin ortadan kalktlgllîlkosullar, canllZldokular için yllZlElZletki meydana getirebilmektedir. Bu yllZIEEletki, insanlar. uzun süreli olarak uzayda kalmalarII önündeki en büyük engel olarak görülmektedir. Insan hücre, doku ve organlarII aglEIIEIleE ortama adaptasyonunu anlamak amacljîla hücre ya da organizma tabanlEl birçok biyoteknolojik metod yaygI olarak kullanllüiaktadlü Fakat uzay yolculuklarII uzun vadedeki en önemli hedeflerinden birisi bu yolculuklar sonunda bir uydu ya da gezegenin kolonize edilmesidir. Örnegin Ay (g=1.6 m/sz) ya da Mars (g=3.7 m/sz) gibi astronomik cisimler üzerinde Dünya'ya oranla daha küçük fakat sülîljan farklElkütle çekimleri bulunmaktadE Teknigin bilinen durumunda bu cisimlerin yüzeylerinde kolonizasyon baslad [gllia oraya adapte olacak ya da orada dogacak insanlarül geçirecegi biyolojik adaptasyonlar ile ilgili öngörü yapmaya yarayacak teknolojiler oldukça limitlidir. State of the Art of the Invention (Prior Art) Mechanical forces play a role in the formation of living tissue and saglllZllZl form and function. It is located between the basic parameters that play and these mechanical forces are eliminated. Kaltlgllîl conditions can create a yearly Handle Effect for living Zlldtissues. This year ZIEE effect, people. as the biggest obstacle to long-term stays in spaceII. is seen. Understanding the adaptation of human cells, tissues and organsII aglEIIEIleE to the environment For this purpose, many cell- or organism-based biotechnological methods are widely used. However, this is one of the most important long-term goals of space travelII. colonization of a satellite or planet at the end of a voyage. For example Moon (g=1.6 m/sz) or on astronomical objects such as Mars (g=3.7 m/sz) sulîljan has different gravitational attraction. In the state of the art, these objects colonization began on their surface [the glilia are people who will adapt or be born there. Technologies that will help to make predictions about the biological adaptations it will undergo are quite is limited.

Uzay biyoteknolojisi konusu yaygI olarak çallgEhamakla beraber, stratejik önem tasIiaktadlE Uzay ile ilgili faaliyetler, haberlesme, gözlem, kesif ve savunma gibi insanslîl olarak yapllâbilecegi gibi, artan bir oranda uzayda insan varl[g]Il10runlu kllâcak gelismelerin de yasanacag Elîbeklenmektedir. Although the subject of space biotechnology is widely discussed, it is of strategic importance. tasliaktadlE Humanitarian activities such as space-related activities, communication, observation, exploration and defense As it can be done, the human existence in space at an increasing rate[g]Il10 It is expected to live in Elî.

Uzay biyolojisi üzerine çallglan bilim insanlari. ortak motivasyonu yerçekiminin degistigi uzay farkllîilioktalara canll]]1g]I gelismesinin mümkün olup olmadlgllüinlamaktlü Bu çerçevede gerçeklestirilen güncel bilimsel çallgmalar etki degeri oldukça yüksek bilimsel çllîtllâr sunabilmektedir. Buna ragmen, uzay biyolojisi konusunda yapllân çallghîalar ya tamamen aglElllllelîl ortam üzerine ya da kütle çekim etkilerini tamamen göz ardlîlederek kimyasal ve termodinamik kompozisyonlar üzerinden yürütülmektedir. Scientists working on space biology. common motivation of gravity whether it is possible to develop the space differentiilioktalara canll]]1g]I change The current scientific studies carried out in this context are scientific studies with a very high impact value. çllîtlllar can present. Despite this, the work done on space biology or completely on the aglElllllelîl environment or completely ignoring the gravitational effects carried out over chemical and thermodynamic compositions.

Prensipte, cisim üzerine etki eden kütle çekim kuvvetlerine ters yönde uygulanan manyetik kuwet aracUJgEIIIe cismin agElliglII klgmî olarak azaltilâbilecegi (manyetik hafiftetme) ve bu sayede uydu ve gezegenlerdeki farklElkütle çekiminlerinin modellenebilecegi bilinmektedir. Teknigin bilinen durumunda manyetik kuwetler cisimlerin Ievitasyonunu saglamak amaclîla kullanilIhlgl ve azaltilüilgl kütle çekimi olusturulmasElamaclýla manyetik kuwetlerin dereceli kontrolünü saglayan bir manyetik hafifletme teknigi daha önce tanIilanmamlStE Bahsi geçen önceki teknikte, CN106471370 numaralEbatent dokümanü heterojen bir hücre toplulugunu manyetik olarak duyarlElbir ortam içerisinde ve manyetik alan gradyende manyetik kuvvet ve yerçekimi kuvvetlerinin dengelendigi pozisyonlari farklHJgllEldan yararlanarak ayßbilen bir sistemi tanIilamaktadE Söz konusu bulus sisteminde hücreler ayrlStEllüiakta ve tamamen aglElllllelîlolarak süspanse bükiüiaktadlü Bu nedenle yer çekiminin klginî olarak azaltIJEiasElve farklEbstronomik ortamlarda etkili olan degisken yer çekiminin biyolojik etkilerinin arastlîlüiasl imkan vermemektedir. In principle, the gravitational forces acting on the object are applied in the opposite direction. With the magnetic force toolUJgEIII, the object's weight can be significantly reduced (magnetic lightening) so that different gravitational pulls on moons and planets can be modeled. known. In the state of the art, magnetic forces are the Ievitation of bodies. It is used to provide the relevant gravitational pull, which is used and reduced A magnetic attenuation technique that provides graduated control of forces has previously been In the aforementioned prior art, Ebatent document number CN106471370 a heterogeneous population of cells in a magnetically sensitive environment and magnetic field positions in the gradient where the magnetic force and gravitational forces are balanced The invention in question describes a system that can know the moon by making use of different hands. In this system, the cells are separated and fully suspended, bent and folded. Therefore, gravity decreases clinically, which is effective in different Epstronomic environments. It does not allow the interrelationship of the biological effects of variable gravity.

Bulusun Klâla Açililamasljlie Amaçlarü Bulusun öncelikli amacElkolonizasyonu planlanan uydu ya da gezegenin kütle çekimini dünyada modelleyebilmektir. Purposes of the Invention The primary purpose of the invention is to detect the gravity of the satellite or planet whose colonization is planned. to model in the world.

Bulus ile canllZhücrelerin üzerindeki aglEllllZ] kuvvetlerini azaltarak, farklEgezegen ve uydulardaki kütle çekimine maruz kalan hücrelerin morfolojik ve fonksiyonel adaptasyonlarll] test edebilecek bir hücre kültürü platformu olusturulmustur. With the invention, by reducing the aglEllllZ] forces on canllZ cells, different planets and planets can be formed. Morphological and functional adaptations of gravitational cells in satellitesll] A cell culture platform has been created to test it.

Bulus konusu olan hücre kültürü platformu, degisen kütle çekim kosullarültlda farkllZl dokular. davran Elarliile ilgili hipotezlerin hücresel seviyede analiz imkânlZile test edilmesine olanak saglamaktadlB Bulus ile Dünya'da yer çekimine maruz kalan tüm kütleler üzerinde olusan aglEllüZl kuwetinin ters yönde ve siddeti ayarlanabilen manyetik kuvvetler araclügllýla istenen oranda azaltliîhasßaglanmaktadm Bulus platformu günes sisteminde kolonizasyon ihtimali bulunan gezegen ve uydularda canllZlhücrelerin gösterecegi mekanik adaptasyonlarEl modellenmesi aç-an tasarlanan ilk ürün olma özelligine sahiptir. The cell culture platform, which is the subject of the invention, differs under changing gravitational conditions. textures. Behave to the testing of hypotheses about Elarliness with the possibility of analysis at the cellular level. enablingdlB With the invention, the pain formed on all the masses exposed to gravity on Earth in the opposite direction of the force and at the desired rate by means of magnetic forces whose intensity can be adjusted. i am underestimating Invention platform is the planet and planet with the possibility of colonization in the solar system. Mechanical adaptations of living cells on satellitesHand modeling on-an It has the feature of being the first product designed.

Bulus uzayda gerçeklestirilen deneylere klýbsla çok daha kolay ve ucuz bir platform sunmakta, uzay biyolojisi konusu ile ilgili bilgi üretimini kolaylastlîlnaylîlve hlîlandünaylîl hedeflemektedir. Invention is a much easier and cheaper platform for experiments carried out in space. presents, facilitates the production of knowledge on the subject of space biology, and facilitates the production of information on the subject of space biology aims.

Bulus aynElzamanda farklEluygulamalarda kullanIi potansiyeli de tasIiaktadlE Diyamanyetik bir cisim üzerindeki kuvvetleri manipüle edebilen bu sistem ve metot dizisi uzay biyolojisi çallgfnalarEl/e mekanik kuvvetlerin biyolojik etkisini inceleyen çalismalar. yanElslß mikro-manipülasyonu bir araç olarak kullanan diger arastlElnalara da etki saglama potansiyeli tasIiaktadIB Örnegin, biyolojik yapllârla temas edecek ve doku ile bütünlük saglamaslîl beklenen biyomateryallerin gelistirilmesinde son derece kritik olan biyomateryal-hücre etkilesim gücü, biyolojik test sistemleri gibi birçok saglllg uygulamasIa önemli olan biyo- molekül afinitesi bu bulusta tan lanacak prensip ile incelenebilmektedir. The invention also carries the potential to be used in different applications at the same time. This set of systems and methods that can manipulate forces on a diamagnetic body biology studiesStudies examining the biological effects of hand/e mechanical forces. sideElslß Potential to influence other research using micro-manipulation as a tool For example, it should come into contact with biological structures and provide integrity with tissue. biomaterial-cell, which is extremely critical in the development of expected biomaterials It is important for many health applications such as interaction strength, biological test systems. molecular affinity can be studied by the principle to be defined in this invention.

Bulusu Aç[liilayan Sekillerin TanlBilarEl Bu bulusla gelistirilen, hücre kültür platformunun daha iyi anlasüâbilmesi için hazlîlianan sekiller asagi açllîlanmaktadE Sekil 1: Paramanyetik ortam içerisinde küresel bir parçacigiE dengelenme öncesi ve sonrasEl üzerine etkiyen kuwetler (Önceki Teknik). The Gods of Figures Opening the Invention Prepared for better understanding of the cell culture platform developed by this invention. Figures are opened below Figure 1: Before and after equilibration of a spherical particle in a paramagnetic environment forces acting on it (Prior Art).

Sekil 2: Manyetik kuvvet vektörü (FM) ve yerçekimi vektörünün (F9) etkisi ile; manyetik Sekil 3: Silindirik ve delikli tip neodimiyum mIIZhatlglar arasIa konumlandlElBwEl hücre kültürü platformundan olusan, hücreler üzerinde kismi aglîllilîl yüklemesi saglayan bulus Sekil 4: Silindirik ve delikli tip neodimiyum m[lZhat|5lar arasIa konumlandEllBilSl hücre kültürü platformundan olusan bulus sistemi içerisinde, (A) 30, (B) 45 ve (C) 60 mM Gd3+ konsantrasyonu içeren ortamda süspanse edilmis 1.05 g/mL yogunluga sahip hücrelere alt mllZhatE yüzeyinde ve alt mllZhatEtan belirli uzaklllîlarda (a: mlEhatE yüzeyi, b: 0.5 mm uzaklllg c: 1 mm uzakl[lZl d: 1.5 mm uzakl[lZl) etki eden toplam ivmeyi gösterir grafikler. Figure 2: With the effect of magnetic force vector (FM) and gravity vector (F9); magnetic Figure 3: Cylindrical and perforated type neodymium wirelines positioned between the ElBwEl cell Invention consisting of a culture platform providing partial loading of aglillilyl on cells Figure 4: The cylindrical and perforated type neodymium m[lZline|5 cells positioned between EllBilSl (A) 30, (B) 45 and (C) 60 mM Gd3+ cells with a density of 1.05 g/mL suspended in medium containing On the mlLZhatE surface and at certain distances from the lower mlLZhatEtan (a: mlEhatE surface, b: 0.5 mm Distance c: Graphics showing the total acceleration acting at a distance of 1 mm [lZl d: at a distance of 1.5 mm [lZl].

Hücreler üzerindeki ivme degisimi COMSOL Multiphysics modelleme yaz[l]]îiil:l ile çözümlenmistir. Change in acceleration on cells with COMSOL Multiphysics modeling yaz[l]]iiil:l has not been resolved.

Sekil 5: Silindirik ve delikli tip neomydium mllZhatlglar arasIa konumlandlEIIBiE hücre kültürü platformundan olusan bulus sistemi içerisinde, (A) 30, (B) 45 ve (C) 60 mM Gd3+ konsantrasyonu içeren ortamda süspanse edilmis 1.1 g/mL yogunluga sahip hücrelere alt mllZhatlîl yüzeyinde ve alt milZhatEtan belirli uzakliEIarda (a: m[lZhatlg yüzeyi, b: 0.5 mm uzakltlg, c: 1 mm uzaklilîl d: 1.5 mm uzakllKD etki eden toplam ivmeyi gösterir grafikler. Figure 5: Cylindrical and perforated type neomydium mllZhatlglar positioned EIIBiE cell (A) 30, (B) 45 and (C) 60 mM Gd3+ cells with a density of 1.1 g/mL suspended in medium containing mllZhatlîl surface and lower milZhatEtan at certain distances (a: m[lZhatlg surface, b: 0.5 mm Graphs showing the total acceleration acting at a distance of c: 1 mm at a distance of d: 1.5 mm at a distance of KD.

Hücreler üzerindeki ivme degisimi COMSOL Multiphysics modelleme yazlüElilîl ile çözümlenmistir. Acceleration change on cells with COMSOL Multiphysics modeling software Elilîl has not been resolved.

Bulusu Olusturan UnsurlarIII/KIEIIE'iIar[Parçalar TanlB'ilarEl Bu bulusla gelistirilen canlEhücrelerin üzerindeki aglEllilg kuvvetlerini azaltarak, farklEI gezegen ve uydulardaki kütle çekimine maruz kalan hücrelerin morfolojik ve fonksiyonel adaptasyonlarIiZtest edebilecek hücre kültürü platformunun daha iyi açiElanabilmesi için hazlîibnan sekillerde yer alan parçalar/k-ilar/unsurlar ayrEayrEhumaralandIElBiEI olup her bir numaranE açiElamasßsag- verilmektedir. 1: Delikli Neodimiyum (N52) M[Ehatlîl 2: Hücre Kültür Platformu 3: Hücre Kültür LamEi 4: YapEkan Band : Delinmis Polimer Kuyu D: Denge Pozisyonu Z: Hücre Kültürü Haznesinin Zemini Bulusun AyrItfülIAçüilamasEl Manyetik prensipler: Siîlîiçerisinde hücre kültürü haznesinin zemini (Z) üzerinde bulunan ve manyetik kuwet etkisindeki bir parçacüZl (ya da hücre) üzerine sistemde denge pozisyonuna (D) gelene kadar etki eden net kuvvet (FA/et): manyetik kuvvet (FM), sürüklenme kuweti (FD) ve yerçekimi kuwetinin (FG) bileskesidir (denklem 1 seti) (Sekil 1). Bu sistemde, eylemsizlik kuvveti (inertial force, F,) mikroaklgkan manyetoferizindeki düsük Reynolds sayEEl sebebiyle, Brownian kuwetin (F5) ise sadece yeterince küçük parçaciEIarI (yaklasiEl olarak 510 nm) hareketini anlamllîdlerecede etkilemesi sebebiyle göz ardlîdilebilmektedir. Invention ElementsIII/KIEIIE[Parts GodsHand By reducing the network forces on living cells developed with this invention, different morphological and functional cells of gravitational cells on planets and moons In order to better explain the cell culture platform that can test the adaptations The parts/things/elements in the hazliibnan figures are AyrEayrEhumaralandIElBiEI and each A number is given to the Elamasßsag-. 1: Perforated Neodymium (N52) M[Ehatlîl 2: Cell Culture Platform 3: Cell Culture LamEi 4: YapEkan Band : Drilled Polymer Well D: Balance Position Z: Cell Culture Chamber Base Detailing the Invention Magnetic principles: On the floor (Z) of the cell culture chamber inside the silica Equilibrium in the system on a particle (or cell) located under the influence of magnetic force net force (FA/et) until position (D): magnetic force (FM), drift force (FD) and gravitational force (FG) (set of equation 1) (Figure 1). In this system, inertial force (F,) low Reynolds sayEEl in microfluidic magnetophoresis Because of this, the Brownian force (F5) only contains sufficiently small particles (approximately) 510 nm) can be ignored because it significantly affects the motion.

FNet=îd+F7+F7 ise ma=îj+îJ+Fî Bir parçacllîl üzerine etki eden FM; B: manyetik aklîlyogunlugu (Tesla, T), V: del operatörü, ü : manyetik dipol degerlerine bagIIE (denklem 2). B milZhat- yüzeyinden uzaklastllîça azalmaktadlE Buradan paramanyetik tuz solüsyonunda ya da ferro slîllçerisinde düsük manyetik alanda üretilen manyetik dipole ulasilâbilmektedir (denklem 3). If FNet=îd+F7+F7 then ma=îj+îJ+Fi FM acting on a particle; B: magnetic intelligence density (Tesla, T), V: del operator, ü : depending on the magnetic dipole valuesIIE (equation 2). B milZhat- from the surface It decreases with distance. From here in paramagnetic salt solution or in ferrous The magnetic dipole produced in the low magnetic field can be reached (equation 3).

H,“:mvß (2) ve magi (3) Bu denklemde; i/E parçac[g]I hacmi, po: boslugun geçirgenligi (1.2566 x10'6 kg'm'A'Z's'z), Ax: parçacllZl ile onu çevreleyen ortamI manyetik duygunluk (magnetic susceptibility) farklîüxp-xm) olarak düzenlenerek FM degeri ifade edilebilmektedir (denklem 4). H,“:mvß (2) and magi (3) In this equation; i/E particle[g]I volume, po: permeability of space (1.2566 x10'6 kg'm'A'Z's'z), Ax: the magnetic susceptibility (magnetic susceptibility) of the particlecllZl and the surrounding environment FM value can be expressed by arranging susceptibility as different (equation 4).

(E. @E kartezyen koordinat sisteminde genisletilerek: (B. V)B= kßxaîwyîyw'î_y) (5) üç boyutta manyetik aklZIdegerIerine ulasllâbilmektedir. Belirtilen kosullarda küresel bir parçaclgll üzerine etki eden bir diger kuvvet olan süekme kuweti (drag force) FD; R (parçaclglE çapm n (dinamik viskozite), @(5ürüklenme katsaymve vpj/e (parçaciglliîl hlîm baglüilarak degisecektir (denklem 6). = 6nRnfd(vp) (6) ParçaclEl üzerine etki eden diger kuvvet FG ise; I/: parçaclgll hacmi, Ap : parçaclEl ile onu çevreleyen ortamI hacimsel yogunluk farkllûp- pm), g. yerçekimi ivmesi (9.8 m's'z) baglEl olarak hesaplanabilmektedir (denklem 7). (Expanding E. @E in the Cartesian coordinate system: (B. V)B= kßxaîwyîyw'î_y) (5) magnetic intelligence values can be reached in three dimensions. under specified conditions, a global Drag force FD, which is another force acting on particles; R (particle diameter n (dynamic viscosity), @(5 drag coefficient and vpj/e (particiglliîl hlîm) will vary depending on (equation 6). = 6nRnfd(vp) (6) If the other force acting on the particle is FG; I/: piececlgll volume, Ap : piececlGll with it volumetric density difference in the surrounding environment, g. gravitational acceleration (9.8 m'z) relative can be calculated as (equation 7).

F7 = Vûpg (7) Bu durumda, parçacgl denge noktasi (D) ulasana kadar Üzerine etki eden kuwet düzenlenerek (denklem 8) denge noktasi (D) ulasI[g]Ia parçacigll hElElÜEolacagEiçin (FD: 0) FNetküresel parçaclgll denge haline göre düzenlenebilmektedir (denklem 9). F7 = Vûpg (7) In this case, the force acting on it, until the particle equilibrium point (D) is reached. (Equation 8) to reach the equilibrium point (D) (FD: 0) FNet can be arranged according to the global particle equilibrium state (equation 9).

FNet - +m)(B V)B + 6uRnfd(vp) + V(pp- :w )9 (8) ve Hücreler gibi diyamanyetik olan parçacilîlar manyetik alan uygulandigiia manyetik alana antiparalel sekilde hizalanmlgl bir manyetik dipol olusturmakta ve bu sebeple manyetik alanlEl minimum oldugu alana dogru bir manyetik kuvvet olusmaktadlEl Olusan bu manyetik dipol ise parçacllîl ile onu çevreleyen ortamI manyetik duygunluk degerine göre degismektedir. Bulusta, yukarüia ayrütllârüa açllZlanan fiziksel olaylardan yararlanüârak platform içerisindeki hücrelerin üzerine etki eden manyetik kuvvetin ve dolayisiyla net kuwetin azaltllE'iaslsîl besi ortamII manyetik duygunluk degeri (xm) ve manyetik akEl yogunlugu (B) degistirilerek saglanmaktadE Hücreleri çevreleyen besi ortamin manyetik duygunluk degeri, besi ortam. farkIElkonsantrasyonIarda paramanyetik iyon ilave edilerek, hücrelerin bulundugu ortam& manyetik akEIyogunIugu ve dagilIEliElise mllZhatlîI ya da mllZhatElarI farkIESekillerde yerlestirilmesi ile elde edilmektedir. Sonuç olarak hücrelerin üzerine etki eden yerçekimi kuvveti istenen ölçüde azaltllârak bu degisikligin biyolojik etkilerinin arastlElIhasElçin kullanllâbilecek bir platform ortaya konmaktadE(Sekil 2).Bulus hücresel uygulamalar için manyetik kuvvetleri kullanan yer çekimi platformu olup, silindirik ve delikli tip neodimiyum mllZhatlîl (1) üzerinde konumlandlEllEilgl hücrelerin üzerine etki eden net kuweti yerçekimine ters yönde magnetik kuwet olusturarak azaltan, hücre kültürü lamII ürerinde yer alan , delinmis bir polimer kuyu (5) içeren bir hücre kültürü platformu(2) olarak karakterize edilmektedir. FNet - +m)(B V)B + 6uRnfd(vp) + V(pp- :w )9 (8) and Particles that are diamagnetic like cells are magnetic when a magnetic field is applied. It creates a magnetic dipole aligned antiparallel to the field, and therefore the magnetic dipole A magnetic force is formed towards the area where the area is minimum. The dipole, on the other hand, is based on the magnetic susceptibility value of the particles and the surrounding environment. is changing. In the invention, by making use of the physical events explained in detail above, the magnetic force acting on the cells in the platform and therefore the net magnetic susceptibility value (xm) and magnetic flux It is provided by changing the density (B) of the magnetic medium surrounding the cells. emotional value, nutrient medium. By adding paramagnetic ions at different concentrations, the environment & magnetic flux density and distribution in which cells are found mllZhatElarI is obtained by placing them in different shapes. As a result, cells By reducing the gravitational force acting on it to the desired extent, this change is biologically A platform that can be used for researching its effects is presented (Figure 2). It is a gravity platform that uses magnetic forces for cellular applications. perforated type neodymium located on mllZhatlîl (1) acting on the cells Cell culture, which reduces the net force by creating a magnetic force in the opposite direction to gravity A cell culture platform (2) with a punctured polymer well (5) located on lamII is characterized as.

Bahsi geçen silindirik ve delikli tip neodimiyum mllZhat- (1) hem olusturdugu manyetik kuwet vektörü düzenli ve yüksektir, hem de ortasIda bulunan delik mikroskopta dogrudan hücre görüntülemesine izin vermektedir. MilZhat- (1) üzerine yerlestirilen hücre kültürü platformu (2), hücre kültürü larnII (3) (hücre kültürü yüzeyi) üzerine yaplgkan bant (4) ile birlesen hassas olarak delinmis bir polimer kuyudan (hücre kültürü haznesi) (5) olusmaktadü Hücre kültürü yüzeyinin mllZhatlgan (1) uzakl[g]ü kültür yüzeyinde bulunan hücrelerin üzerinde olusan ters ivmelenmenin siddetini belirleyen bir faktördür. Bu ters ivmelenme mEIZhatlEtan (1) uzaklasliEça azalmaktadIE Hücreler üzerinde yer çekimine ters yönlü ivme yaratabilen ve kismi aglflllEl yüklenmesini saglayan bu sistem; hücre kültürü platformunun (2) alt. ve üstüne, aynlZl kutuplarEl birbirine dönük olacak sekilde konumlandEIJ-:hlg delikli N52 neodimiyum milihatlâlardan (1) 0lusmaktadB(Sekil 3). Bu platformda, alt mllZhatE yüzeyinde ve alt miIZhatEtan belirli uzaklllZIarda hücrelere etki eden ivme COMSOL Multiphysics modelleme yazl]]]îlil:lle çözümlenmistir. FarklEl/ogunluklara sahip hücreler üzerindeki aglEllllZl kuvvetlerinin bu bulus ile azaltüâbilecegini göstermek amaclîla, bu sistem ile yogunlugu 1.05 g/mL (Sekil 4) ve 1.1 g/mL (Sekil 5) olan hücreler üzerine etki eden ivmelenme modellenmistir. Bu modelleme yap[[[lîlken hücrelerin üç farkIEGadoIinyum (III) (Gd3+) konsantrasyonunda süspanse edildigi durumda alt mlEhatlgl yüzeyinde ve yüzeyden 0.5, 1 ve 1.5 mm uzakllElarda hücreye etki eden ivmelenme modellenmistir. The aforementioned cylindrical and perforated type neodymium mllZhat- (1) both formed The magnetic force vector is regular and high, and the hole in the middle is in the microscope. Allows direct cell viewing. Cell placed on MilZhat- (1) adhesive tape on culture platform (2), cell culture larnII (3) (cell culture surface) (4) from a precision-drilled polymer well (cell culture chamber) converging with (5) mllZhatlgan (1) distance[g] of the cell culture surface It is a factor that determines the severity of the reverse acceleration on the cells. This is reverse acceleration mEIZhatlEtan (1) decreases with distance This system, which can create directional acceleration and provides partial loading; cell culture (2) bottom of the platform. and on top of it, with the opposite poleshand facing each other. positionedEIJ-:hlg perforated N52 neodymium rods (1) consisting of 0(Fig. 3). This on the platform, on the lower mlZhatE surface and on the lower miIZhatEtan, which acts on cells at certain distances. The acceleration is analyzed with the COMSOL Multiphysics modeling software]]]ilil:ll. having different/health In order to show that aglEllllZl forces on cells can be reduced by this invention, this effect on cells with a density of 1.05 g/mL (Figure 4) and 1.1 g/mL (Figure 5) with the system. acceleration is modeled. Do this modeling[[[lîlken cells three differentIEGadoIinium (III) (Gd3+) in the sub-mlEhatlgl surface when suspended in concentration and The acceleration acting on the cell is modeled at 0.5, 1 and 1.5 mm distances from the surface.

Grafiklerdeki (Sekil 4 ve Sekil 5) pozitif ivme degerleri yerçekimi kuvveti ile aynü/öndedir ve sonuçlar seçilen yüzey ve uzakllEJarda hücreler üzerindeki agEIliKi kuvvetlerini azaltacak sekilde gerekli ivmelenmenin sistem tarafIdan saglanabilecegini göstermektedir. The positive acceleration values in the graphs (Figure 4 and Figure 5) are the same/leading with the gravitational force and The results will reduce the forces of AgEI on cells at selected surfaces and distances. The figure shows that the required acceleration can be provided by the system.

Yukarßla açlElanan ve hücreler üzerinde yer çekimine ters yönlü ivme yaratabilen sistem benzer sekilde; (I) hücre kültürü platformunun sadece altlEb delikli milZhatlîl yerlestirerek ve (ii) hücre kültürü platformunun altlEta, deliginin içerisine aynlîlkutuplarEl birbirine dönük olacak sekilde baska bir silindirik mlEhatlîI konumlandlElEiE delikli mlEhatEI yerlestirerek de olusturulabilmektedir.As explained above, which can create acceleration in the opposite direction to gravity on the cells. system in a similar way; (I) the bottom of the cell culture platform only and (ii) separation poles into the bottom, hole of the cell culture platform. mEhatEI with holes in another cylindrical position, facing each other It can also be created by placing

Claims (1)

ISTEMLER . Hücresel uygulamalar için manyetik kuvvetleri kullanan yerçekimi platformu olup Özelligi; en az bir miighatlîl (1) üzerine konumlandlElIJ-:hlgl hücrelerin üzerine etki eden net kuvveti yerçekimine ters yönde manyetik kuvvet olusturarak azaltan, hücre kültürü IamIlEl (3) üzerinde yer alan, delinmis bir polimer kuyu (5) içeren bir hücre kültür platformu (2) olarak karakterize edilmesidir. . Istem 1'e uygun hücre kültür platformu olup özelligi; hücre kültürü platformunun (2) alt. ve üstüne, ayn Ekutuplarlîiîbirbirine dönük olacak sekilde konumlandiEilIhlgi miEhatlglarI silindirik ve/veya delikli tip neodimiyum milihatlîlolmas- . Istem l'e uygun hücre kültür platformu olup özelligi; hücre kültür platformunun hücre kültür IamEiiIe söz konusu IamI üzerinde yaplgkan bant (4) ile birlestirilmesidir. . Hücre kültür platformu haziEliama yöntemi olup özelligi; platform içerisindeki hücrelerin üzerine etki eden manyetik kuvvetin arttlEIliîasDve dolayElsîla net kuwetin azaltlEhaleliEl; besi ortamiEliEl manyetik doygunluk degeri (xm) ve manyetik akiÃiogunlugu (B) degistirilerek saglanmasIEi . Istem 4 `e uygun hücre kültür platformu hazlElianma yöntemi olup özelligi; hücreleri çevreleyen besi ortamII farkIEmanyetik doygunluk degerlerinin (xm), besi ortam. farkliZIkonsantrasyonIarda paramanyetik iyon ilave edilmesi ile saglanmasIE . Istem 4 `e uygun hücre kültür platformu hazlIlianma yöntemi olup özelligi; hücrelerin bulundugu ortamI fakllîh'ianyetik akEyogunIugu ve daglIIEiiII en az bir miEhat- farklEfekilIerde yerlestirilmesi ile elde edilmesidir.REQUESTS . It is a gravity platform that uses magnetic forces for cellular applications. a cell culture platform (2) with a punctured polymer well (5) located on the cell culture glass (3), which reduces the net force acting on the cells with a magnetic force in the opposite direction to gravity, positioned on at least one miighatlil (1). ) is characterized as . It is a cell culture platform according to claim 1 and its feature is; the bottom of the cell culture platform (2). and on top of it, cylindrical and/or perforated type neodymium milia- It is a cell culture platform according to claim 1 and its feature is; is to connect the cell culture platform with the cell culture IamEi to the adhesive tape (4) on the said IamI. . The cell culture platform is the method of preparation and its feature is; The magnetic force acting on the cells in the platform is increased and therefore the net force is decreased. The nutrient medium should be provided by changing the magnetic saturation value (xm) and magnetic flux density (B) . It is the method of preparation of the cell culture platform in accordance with claim 4 and its feature is; The nutrient medium surrounding the cells II is the difference of the magnetic saturation values (xm), nutrient medium. It is provided by adding paramagnetic ions at different ZI concentrations. It is a cell culture platform preparation method in accordance with claim 4 and its feature is; The environment in which the cells are located is obtained by placing them in at least one miEhat- different effects.
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