【発明の詳細な説明】本発明は液体精製等に用いる透析法に関する。[Detailed description of the invention]The present invention relates to a dialysis method used for liquid purification and the like.
この方法は特に実験分析の反復用途に有用である。This method is particularly useful for repeated applications in experimental analysis.
透析法は蛋白質やペプチド類の様な溶液中の透析出来る
塩類又は高分子量成分から低分子量成分を分離すること
によって蛋白質、ペプチド類を測定するか又はその場で
分析目的を達することが必要である場合の血液の様な生
物学的液体の分析にしばしば用いる操作である。The dialysis method is necessary to measure proteins and peptides by separating low molecular weight components from dialyzable salts or high molecular weight components in solutions such as proteins and peptides, or to achieve the analytical purpose on the spot. This is a procedure often used in the analysis of biological fluids such as blood.
広（使われている透析法の１実験分析用途は癌の処置お
よび診断の助けとなる試験管テストである癌胚芽抗原分
析においてである。この試験で血液蛋白質類を過塩素酸
で血漿試料から沈澱させ次いで放射免疫分析を用いて上
澄液中の癌胚芽抗原の測定をする。これを行う前に大事
なことは血漿試料のオスモラリチー（ＯＳ■ｏｌａｌｉ
ｔｙ）を低い水準に保ちながら脱蛋白質化した血漿試料
から過剰の酸度を除去する工程である。透析法はこれら
の目的に使われるもので本発明は従来法の改良法である
。One experimental analytical use for dialysis is in cancer germ antigen analysis, a test tube test that aids in the treatment and diagnosis of cancer. In this test, blood proteins are extracted from plasma samples with perchloric acid. After precipitation, carcinoembryonic antigens in the supernatant are measured using radioimmunoassay.Before doing this, it is important to determine the osmolality of the plasma sample.
ty) to remove excess acidity from a deproteinized plasma sample while maintaining a low level of acidity. The dialysis method is used for these purposes, and the present invention is an improvement on the conventional method.
現在行われている癌胚芽抗原分析の１方法は次の工程に
よろ：（１） 血ＩＩ 試１） ０．５ｍ ｌ ＋ ０．８
５％塩化ナトリウム２１ｍ１で稀釈する。One currently used method for cancer germ antigen analysis involves the following steps: (1) Blood II Test 1) 0.5 ml + 0.8
Dilute with 21 ml of 5% sodium chloride.
（２） １．２Ｍ過塩素酸２５ｍｊを加える。(2) Add 25mj of 1.2M perchloric acid.
（３） １００ＯＸ ｇで２０分間遠心分離する。(3) Centrifuge at 100OXg for 20 minutes.
（４）上澄液を透析袋に移す。(4) Transfer the supernatant to a dialysis bag.
（５）脱イオン水に対し透析し終わりに０． ＯＩＭｊ
酢酸アンモニウムに対し最終ｐＨ６，５±０．２迄透析
する。(5) At the end of dialysis against deionized water, 0. OIMj
Dialyze against ammonium acetate to a final pH of 6.5±0.2.
（６）精製した溶液を次の特徴をもつ放射免疫分析法で
分析する。(6) Analyze the purified solution using a radioimmunoassay method with the following characteristics.
（ａ） 溶液に癌胚芽抗原抗血清を過剰に加える。(a) Add an excess of carcinoembryonic antigen antiserum to the solution.
（ｂ） 培養して抗原−抗体複合体を生成させる。(b) Cultivate to produce an antigen-antibody complex.
（ｃ） １１２１１−癌胚芽抗原を過剰に加えて過剰
の抗体と反応させる。(c) 11211-Carcinoembryonic antigen is added in excess and reacted with excess antibody.
（ｄ） 抗原−抗体複合体をりん酸ジルコニルゲル上
に吸着させて除去する。(d) The antigen-antibody complex is removed by adsorption onto zirconyl phosphate gel.
（ｅｌ ゲルを回収しその！ 含有量をガンマシン
チレーシ璽ン分光計で測定する。(Recover the gel and measure its content using a gamma scintilage spectrometer.
本発明の方法をたとえば上記の分析に利用する場合その
対象は工程５に関する。これは過剰の過塩素酸と血漿試
料からの他の低分子量成分を透析によって除去してｐＨ
６，５±０．２でイオン性強度０． ＯＩＭの非蛋白質
血漿成分と癌胚芽抗原の溶液をつくるのである。ｐ）［
とイオン強度に関するこの基準は放射免疫分析をうまく
使うには大切なことである。When the method of the invention is used, for example, in the above-mentioned analysis, its object relates to step 5. This is done by removing excess perchlorate and other low molecular weight components from the plasma sample by dialysis and adjusting the pH
6,5±0.2 and ionic strength 0. A solution of OIM's non-protein plasma components and carcinoembryonic antigens is created. p) [
This criterion of ionic strength and ionic strength is important for the successful use of radioimmunoassay.
この従来法を行うには脱蛋白質化した血漿試料を透析袋
に入れて血漿試料容量当たりｓｏ倍量の水を含む静止浴
に対し透析する方式を用いている。This conventional method uses a method in which a deproteinized plasma sample is placed in a dialysis bag and dialyzed against a static bath containing so many times the amount of water per volume of the plasma sample.
血漿試料中の最終ｐＨとイオン強度についての要請を充
足する為には透析浴を３時間おきに３回変えた後０．０
１Ｍ酢酸アンモニウム溶液に対して最終透析することが
必要としている。自動装置使用にも拘らずこの透析法は
時間がか−り馴れた人の注意が必要でありかつ装置は実
験室の広い場所を占領する。本発明はこれらの点につい
て改良法を提供するものである。0.0 after changing the dialysis bath 3 times at 3 hour intervals to meet the requirements regarding the final pH and ionic strength in the plasma sample.
A final dialysis against 1M ammonium acetate solution is required. Despite the use of automated equipment, this dialysis method is time consuming and requires the attention of an experienced person, and the equipment occupies a large amount of laboratory space. The present invention provides an improved method in these respects.
透析されるべき液が入っている半透膜を浸漬する液体透
析媒質を入れる容器を使い上記容器の入口をとおして新
透析媒質を連続して流し込み上記容器の出口をとおして
透析物を含む透析媒質を連続して除去する透析法におい
て、本発明は上記入口および出口の間の上記媒質全体中
に層流状態を保つ改良法を提供するものである。Dialysis using a container containing a liquid dialysis medium in which a semipermeable membrane containing the liquid to be dialysed is immersed, and fresh dialysis medium continuously flowing through the inlet of said container and containing dialysate through the outlet of said container. In dialysis processes where media is continuously removed, the present invention provides an improved method of maintaining laminar flow conditions throughout the media between the inlet and outlet.
上記の透析法に有効な透析槽は両端と両側面と底をもっ
た長い容器より成り、両側面は形が実質的に同じで、両
端と両側の上部端はふちになっており下端は槽の底につ
けられて水が漏れない様になっており、側面にそった容
器の長さに比べて端における容器の巾は比較的せまい：
この容器内の垂直横の隔板は平面図で容器の一端に平行
にすぐ接近してしかし間隔をおいて固定し容器の底と両
側面につけられて上部が開放した区画室をなしその板の
上端は水平で容器の最上端より低い：透析媒質の入口は
上部開放区画室の最下端にあり容器の外部と通じている
；容器内の透析媒質の唯一の出口は容器の上記板から最
も遠い端の下端にある；溢流口は上記出口と連絡してお
り透析操作中上記容器中の透析媒質が過剰となった場合
透析媒質が上記容器から排出されて上記容器内の上記媒
質の水位が上記隔板の最上端と実質的に同一に保たれる
様な位置にある。The dialysis tank useful for the dialysis method described above consists of a long container with ends, sides and a bottom, the sides being substantially the same in shape, the ends and upper ends of both sides being rimmed, and the lower end of the container being a tank. The width of the container at the end is relatively narrow compared to the length of the container along the sides:
Vertical transverse partitions in this container are fastened parallel to one end of the container in plan, close together but spaced apart, and are attached to the bottom and sides of the container to form compartments open at the top. The top edge is horizontal and lower than the top edge of the container: the inlet for the dialysis medium is at the lowest end of the open top compartment and communicates with the exterior of the container; the only outlet for the dialysis medium in the container is furthest from the above plate of the container. at the lower end of the end; an overflow port communicates with the outlet so that during dialysis operation, if there is an excess of dialysis medium in the container, the dialysis medium is drained from the container and the level of the medium in the container is increased. The position is such that it remains substantially the same as the uppermost edge of the diaphragm.
上記した癌胚芽抗原分析における血清試料透析において
従来の装置が槽容積５１当たり約２０試料の能力をもっ
ているのに対して本発明を用いると容積約６１で透析能
力約５０試料である。本発明の方法は試料が透析される
液媒質の層流を用いるものでありこれはより小さな槽の
使用を可能にし実験者の必要する注意を軽減する。同時
に血漿試料の精製度も改良する。この特長の結果当然−
走度の精製に要する時間の減少ともなる。In the dialysis of serum samples in the cancer germ antigen analysis described above, the conventional apparatus has a capacity of about 20 samples per tank volume of 51, whereas the present invention has a capacity of about 50 samples per tank volume of about 61. The method of the present invention uses laminar flow of the liquid medium in which the sample is dialyzed, which allows the use of smaller vessels and reduces the required attention of the experimenter. At the same time, the degree of purification of plasma samples is also improved. Naturally, the result of this feature is -
This also reduces the time required to refine the running speed.
出願者の知る限り透析媒質を層流に保持する属性は未ｔ
！認められていないので本発明の基礎となっている。To the applicant's knowledge, there is no attribute that maintains the dialysis medium in laminar flow.
! This is the basis of the present invention.
本発明を付図について説明する。The present invention will be explained with reference to the accompanying drawings.
図Ｉは本発明方法で用いる透析容器の倒立面図である。Figure I is an inverted view of a dialysis container used in the method of the invention.
図■は図Ｘの線２−２にそってとった断面図で図■に示
した容器の入口と隔板を示すものである。Figure ■ is a cross-sectional view taken along line 2--2 in Figure X, showing the inlet and septum of the container shown in Figure ■.
図■は図Ｘの＄３−３にそってとった断面図で図Ｉに示
した容器の出口と溢出口を示すものである。Figure 2 is a sectional view taken along line $3--3 in Figure X, showing the outlet and overflow port of the container shown in Figure I.
図■は図Ｉに示した容器に使う支持枠の側面図である。Figure ■ is a side view of a support frame used for the container shown in Figure I.
図■は図■に示した支持枠の平面図である。Figure ■ is a plan view of the support frame shown in Figure ■.
図■と■は図■に示した支持枠の両端立面図である。Figures ■ and ■ are elevational views of both ends of the support frame shown in figure ■.
図■は図Ｉに示した容器の入口端立面図である。Figure ■ is an elevational view of the inlet end of the container shown in Figure I.
図■は図Ｉに示した容器の出口端立面図である。Figure ■ is an elevational view of the outlet end of the container shown in Figure I.
図Ｘは図■に示した容器の平面図である。Figure X is a plan view of the container shown in Figure ■.
図ＸＩは図工の容器内の図■の支持枠の配置を示す分解
配列透視図である。FIG. XI is an exploded arrangement perspective view showing the arrangement of the support frame of FIG.
図Ｉは本発明方法で用いる型の１例の透析槽１０の倒立
面図である。図■は図工に示した槽の入口端１５の立面
図で、図■は出口端１６の立面図でまた図Ｘは同じ槽の
平面図である。槽１０は長く形が樋型で両ｇＩＪ１５と
１６、両端面２０と２１があり底２５がある。Figure I is an inverted view of a dialysis cell 10 of the type used in the method of the present invention. Figure 2 is an elevation view of the inlet end 15 of the tank shown in the drawing, Figure 2 is an elevation view of the outlet end 16, and Figure X is a plan view of the same tank. The tank 10 is long and has a gutter-like shape, and has both gIJs 15 and 16, both end faces 20 and 21, and a bottom 25.
両端１５と１６は容器の巾をあられし側面２０と２１の
長さより比較的せまい。端１６における槽の深さは端１
５における深さより幾分深い方が好ましい。側面２０と
２１は実質的に同じ形である。図工に示した本発明の詳
細な説明すれば槽１０の底２５は端１Ｂに向かって下に
傾斜しているがこれは本質的な特徴ではない。端１Ｂに
向かって下へ傾斜していることは単に槽の排水に便利な
為である。槽１０の上端はムち３０を形成し蓋（図示さ
れていない）をするに適しているが蓋の必要はなく室温
操作の場合蓋を使わぬことが好ましい。室温より実質的
に高いか又は低い温度で操作する場合は槽に蓋をするこ
とが望ましい。The ends 15 and 16 extend the width of the container and are relatively narrower than the length of the sides 20 and 21. The depth of the tank at end 16 is end 1
It is preferable that the depth be somewhat deeper than that in 5. Side faces 20 and 21 are of substantially the same shape. In the detailed description of the invention shown in the drawings, the bottom 25 of the tank 10 slopes downwardly toward the end 1B, but this is not an essential feature. The downward slope toward the end 1B is simply for convenience in draining the tank. The upper end of the tank 10 forms a whip 30 and is suitable for a lid (not shown), but a lid is not necessary and is preferably not used for room temperature operation. It is desirable to cover the vessel when operating at temperatures substantially above or below room temperature.
本発明の方法で操作中の槽内透析媒質の液水位は３５に
よって示され槽内の媒質自体は槽１０のＤｓ１５にある
孔４０によって表わされろ入口から新しい媒質を連続供
給することにより層流に保つことが出来る。同様に過剰
の透析媒質は槽１０の端１６における孔５５によって表
わされる出口から槽の内部と外部の間の水９５０をとお
り孔４５であられされろ溢流口をとおって出る。示され
た好ましい実施態様における隔板６０は上記槽の中に両
側面２０と２１および底２５との間に垂直に横に位置し
て水の漏れぬ様固定されており平面図で入口孔４０をも
っ端１５と接近して平行につけてあり透析媒質３６の表
面水位３５より僅かに下で実質的に殆ど同じ深さから槽
の底２５迄延びて槽中に上の開放した区画室６５を形成
する。The liquid level of the dialysis medium in the tank during operation in the method of the invention is indicated by 35, and the medium in the tank itself is maintained in laminar flow by continuous supply of fresh medium from the inlet, represented by the hole 40 in Ds 15 of tank 10. can be kept. Similarly, excess dialysis medium exits through the outlet represented by hole 55 at end 16 of cell 10 through the water 950 between the interior and exterior of the cell and through hole 45 and the overflow port. In the preferred embodiment shown, a diaphragm 60 is fixed in the tank vertically and laterally between the sides 20 and 21 and the bottom 25 in a water-tight manner, and is connected to the inlet hole 40 in plan view. is placed close to and parallel to the end 15 and extends from a depth slightly below and substantially the same depth as the surface water level 35 of the dialysis medium 36 to the bottom 25 of the bath to form an upper open compartment 65 into the bath. Form.
入口孔４０の近く、透析媒質３Ｂ内、出口孔５５の近く
および排水管４６内に図示した矢印は本発明の方法実施
の際の透析媒質の流れ方向を示している。The arrows illustrated near the inlet hole 40, in the dialysis medium 3B, near the outlet hole 55 and in the drain tube 46 indicate the direction of flow of the dialysis medium during implementation of the method of the invention.
本発明の方法の操作中に典型的になされるとおり透析袋
７０が透析媒質３６内に吊り下げられているのが示され
ている。槽は７０と同様に多数の透析袋を吊り下げて操
作するに適している。透析袋７０は半透膜で出来ており
透析されるべき溶質を含む液体が入っている。この液体
は図中７５で示されている。透析操作中溶質は液７５か
ら袋７０をとおって媒質３６中に拡散し次いで除去され
る。媒質３６中に袋７０を吊り下げる方法はどれでも使
用出来ろ。袋は少なくも袋中に入っているｗ１７５の水
位に相当した深さに吊り下げろ必要がある。図Ｉにおい
て袋７０は充分に浸漬されておりまた完全に液７５で満
たされている。A dialysis bag 70 is shown suspended within the dialysis medium 36 as is typically done during operation of the method of the present invention. The tank, like 70, is suitable for suspending and operating a large number of dialysis bags. The dialysis bag 70 is made of a semipermeable membrane and contains a liquid containing the solute to be dialyzed. This liquid is indicated at 75 in the figure. During the dialysis operation, solutes diffuse from fluid 75 through bag 70 into medium 36 and are then removed. Any method of suspending bag 70 in medium 36 may be used. The bag must be hung at a depth that is at least equivalent to the water level of the W175 contained in the bag. In Figure I, bag 70 is fully immersed and completely filled with liquid 75.
図■は図Ｘの線２−２にそって矢印方向に見た透析槽１
０の端１５と隔板６０の断面図である。図■は端１５に
接近しているがそれから離れて上部開放区画室６５を形
成する隔板６０を示している。透析媒質３６は入口孔４
０から槽１０内に流れ上部開放区画室６５中を上昇し隔
板６０の最上端を越えろ。透析媒質３Ｂの層流は供給速
度が正常にｌ整されていれば右下方向に槽の反対端底方
向に向かう。相当程度の調整が可能である。Figure ■ shows the dialysis tank 1 seen in the direction of the arrow along line 2-2 in Figure X.
FIG. Figure ■ shows a diaphragm 60 close to the end 15 but away from it to form an open top compartment 65. The dialysis medium 36 is connected to the inlet hole 4
0 into the tank 10 and rise through the open top compartment 65 and over the top of the septum 60. The laminar flow of the dialysis medium 3B will flow downward to the right and toward the bottom of the opposite end of the tank if the feed rate is properly adjusted. A considerable degree of adjustment is possible.
図■は図Ｘの線３−３にそって矢印方向に見た透析槽１
０の出口＠１６の断面図である。透析媒質３６は槽１Ｇ
から槽１０の端１６にある水路５０で互いに通じている
出口孔５５と溢流口４５をとおって出ろ。透析媒質３Ｂ
の表面水位３５は溢流口４５の水位で決まる。Dialysis tank 1 is shown in the direction of the arrow along line 3-3 in Figure X.
0 is a cross-sectional view of outlet @16. Dialysis medium 36 is tank 1G
from the tank 10 through an outlet hole 55 and an overflow opening 45 which communicate with each other in a water channel 50 at the end 16 of the tank 10. Dialysis medium 3B
The surface water level 35 is determined by the water level at the overflow port 45.
出口５５は槽１Ｇの下端にある。横ｌＯの底２５の平坦
傾斜面と底２５に接した出口５５の位置は操作終了時に
槽の排水を可能にする。The outlet 55 is at the lower end of the tank 1G. The flat sloped surface of the bottom 25 of the lateral lO and the location of the outlet 55 on the bottom 25 allow draining of the tank at the end of the operation.
図Ｉにおいて溢流口４５は排水管４６に連結しておりそ
れは槽１０からの透析された溶質を含む過剰透析媒質の
溢流を汚水溜、下水又は受槽の様な適当な排水場所に送
る。水路５０ばその上端にこの方法操作中、透析媒質３
６の表面３５より高い位置に空気孔５１をもつ。図■の
装置中空気孔５１は単に水路５０と透析媒質３Ｂの表面
３５よ＾上の位置で大気との間をつなぐ孔である。In Figure I, overflow port 45 is connected to drain pipe 46 which directs the overflow of excess dialysis media containing dialysed solutes from tank 10 to a suitable drainage location, such as a sump, sewer or receiving tank. During operation of this method, the dialysis medium 3 is placed at the upper end of the water conduit 50.
6 has an air hole 51 at a higher position than the surface 35. The air hole 51 in the device shown in FIG.
この方法の終了時又は透析媒質３６を換える為のいずれ
かで槽１０から透析媒質３６を除去するに便利の為、入
口４０からの新透析媒質の供給はバルブ（図示していな
い）を閉じて入口４０からの透析媒質３６の流れを調節
し空気孔５１を閉じて止める。槽１０の排水管４６の末
端が槽１０の底２５より図Ｉに示すとおり下位の位置に
ある場合は空気孔５１を閉じることによって水路５０、
溢流口４５および排水管４６内にサイホンが形成される
。図工において空気孔５１を閉じる為の栓５２を示して
おり孔５１中にかたくつければ水路５０と大気との流通
は断たれる。To conveniently remove dialysis medium 36 from bath 10 either at the end of the process or to change dialysis medium 36, fresh dialysis medium is supplied through inlet 40 by closing a valve (not shown). The flow of dialysis medium 36 from inlet 40 is regulated and stopped by closing air hole 51. If the end of the drain pipe 46 of the tank 10 is located at a lower position than the bottom 25 of the tank 10 as shown in FIG.
A siphon is formed within the overflow port 45 and drain pipe 46. The drawing shows a plug 52 for closing the air hole 51, and if it is firmly inserted into the hole 51, the communication between the water channel 50 and the atmosphere will be cut off.
更に図Ｉに付属装置として透析媒質３６内の種々の深さ
においた検出器１１５．１２０および１２５を示してい
る。除去される特定透析物溶質の為に適当する検出器を
選ぶ。例えば透析袋７０中に含まれる液７５から癌胚芽
抗原分析における様に水素イオンが除去されろならば検
出器１１５．１２０および１２５はｐＨメーターの電極
でよい。透析媒質３６の下方向き層流の為透析された溶
質のより高い濃度が槽の下位で発見され、これは示した
検出器によって監視出来る。FIG. 1 also shows detectors 115, 120 and 125 at various depths within the dialysis medium 36 as ancillary equipment. Select the appropriate detector for the particular dialysate solute being removed. For example, if hydrogen ions are to be removed from the fluid 75 contained in the dialysis bag 70, as in carcinoembryonic antigen analysis, the detectors 115, 120 and 125 may be pH meter electrodes. Due to the downward laminar flow of the dialysis medium 36, a higher concentration of dialysed solute is found in the lower part of the bath, which can be monitored by the detector shown.
操作が終了に近ずくにつれて最も浅い検出＠１２５と最
も深い検出器１１５の間の読みの差が最小となるであろ
う。As the operation nears completion, the difference in readings between the shallowest detection@125 and the deepest detector 115 will be minimal.
本発明の本質的部分を構成するものではないが図■に槽
１０内透析媒質３６内の浸漬位置に多数の透析袋７０を
懸垂する手段として役立つ枠を示す。枠は一般に番号８
０で示す。図Ｖば枠８０の平面図で図■と■はその立面
図である。枠８０は脚９０．９１．９２および９３の上
にのっている下板８５と板８５の両側の間の中心に位置
する支持垂直板９５より成る。垂直板９５は枠８０が断
面“■”形となり４本脚９０〜９３の上にのる樟に上板
ＩＱＱを支える。支持枠８０の寸法は槽ｌＯの両側面２
０と２１および隔板６０と出口端１６の間に図ＸＩに示
すとおり丁度合う寸法とする。検出器１１５．１２０お
よび１２５を使用する場合そのすき間をつくっておく。Although not constituting an essential part of the invention, FIG. The frame is generally numbered 8
Indicated by 0. Figure V is a plan view of the frame 80, and Figures ■ and ■ are elevation views thereof. Frame 80 consists of a lower plate 85 resting on legs 90, 91, 92 and 93 and a supporting vertical plate 95 centrally located between the sides of plate 85. The frame 80 of the vertical plate 95 has a "■"-shaped cross section and supports the upper plate IQQ on a camphor tree that rests on four legs 90 to 93. The dimensions of the support frame 80 are as follows:
0 and 21 and between the diaphragm 60 and the outlet end 16 as shown in FIG. If detectors 115, 120 and 125 are used, a gap should be provided.
支持枠８０の上板１００と下板８５は１０５と１１０で
示す様に互いに垂直に整合する一連のスロットをもって
いる。スロットは透析袋７０の上端と下端の結び目を差
し込むに適している。透析袋は適当な長さのセロファン
管の下端を結び透析されるべき溶質を含む液を袋に満た
した後管の上端を結んで便利につ（ろ。結び目の内側の
袋の上と下のくびれな部分を互いに合ったスロット１０
５と１１０内に差し込んで上の結び目が板１００の上に
支えられ下の結び目が板８５の下に保たれる様にする。The upper plate 100 and lower plate 85 of the support frame 80 have a series of slots shown at 105 and 110 that are vertically aligned with each other. The slots are suitable for inserting the knots at the top and bottom ends of the dialysis bag 70. To make a dialysis bag, tie the bottom end of an appropriate length of cellophane tube, fill the bag with the solution containing the solute to be dialyzed, and then tie the top end of the tube. Slot 10 with parts aligned with each other
5 and 110 so that the upper knot is supported on the plate 100 and the lower knot is kept under the plate 85.
枠８０は適当に間隔をもっｔコ多数のスロットが７０と
同じ多数の透析袋を懸垂状態で支える様な構造になって
いる。Frame 80 is constructed such that a number of suitably spaced slots support the same number of dialysis bags as 70 in suspension.
本発明で用いうろ別の余り好ましくない透析容器は図Ｉ
に示すものと同じであるが隔板６０がなく上部開放区画
室６５がなくて入口孔４０が直接槽内部と通じているも
のである。この場合入口孔４０が透析媒質３６の表面３
５に近い端１５の上端に位置しており成るべ（出口孔４
５と実質的同じ深さが好ましい。Another less preferred dialysis container for use in the present invention is shown in Figure I.
This is the same as that shown in Fig. 1, but without the partition plate 60 and the open top compartment 65, so that the inlet hole 40 directly communicates with the inside of the tank. In this case, the inlet hole 40 is located at the surface 3 of the dialysis medium 36.
5 is located at the upper end of the end 15 (outlet hole 4
5 is preferred.
本発明の層流透析方法の利点を例証する為ｙ！ＪＩに示
しｔコと同じ透析槽を使って３回実験を行った。To illustrate the advantages of the laminar flow dialysis method of the present invention! Experiments were conducted three times using the same dialysis tank as shown in JI.
図１の７５で示される透析されるべき溶質を含む液とし
て硫酸鋼溶液を使用し透析の進行を透析媒質３６中に蓄
積される銅塩としての溶液を青色から肉眼で推定しｔコ
。透析は透析媒質として水に対して行った。この操作の
効率の定量的測定は試験終了時袋７０中の透析された液
７５の分析によって行っな。Using a steel sulfate solution as a solution containing the solute to be dialyzed, shown at 75 in FIG. 1, the progress of dialysis is visually estimated from the blue color of the solution as a copper salt accumulated in the dialysis medium 36. Dialysis was performed against water as the dialysis medium. A quantitative measure of the efficiency of this operation is made by analysis of dialysed fluid 75 in bag 70 at the end of the test.
第３試験（本発明）においては図Ｉに示したと同じ容量
６１の槽を使った。第１試験（バッチ）及び第２試験（
乱流）においては図■に示したと同じ横であるが隔板６
０がな（入口孔４０が端１５の上端にあり容′ｊ＃、６
１の槽を使った。透析袋２４個に０、７５Ｍ硫酸鋼各Ｓ
ｒａｇを入れ５．８８１の水を入れた槽内に吊るした。In the third test (invention), the same 61 volume vessel as shown in Figure I was used. First test (batch) and second test (
In case of turbulent flow), the same horizontal as shown in Figure ■, but the partition plate 6
0 (the inlet hole 40 is at the upper end of the end 15 and the capacity is 'j#, 6
I used tank 1. 24 dialysis bags each made of 0 and 75M sulfuric acid steel
rag and hung it in a tank filled with 5.881 g of water.
最初の試験は従来法によって行い透析媒質は静止させて
おいたが９時間の試験中３時間おきに除去して入れかえ
た。かくて透析媒質として水金量１７６４を使ってそれ
ｔこ対し透析液０．１２オが透析された。この比は１４
７で透析された液１容量当たり透析媒質１４７容量が使
われたことを示している。第２および第３試験において
透析槽１０をとおる透析媒質の連続乱流および連続層流
の両条件で同じ装置を使用した。この両試験では各５ｍ
ｌのＱ、 ７５Ｍ硫酸銅を入れたセロファン透析袋４６
個を用い（透析されるべき全液量０．２１）９時間の量
水全量３４．５１に対し透析した。この両試験において
透析媒質の透析された液に対する比率１５０でこれは従
来法の静止透析におけるものと実質的に同率であった。The first test was carried out conventionally, with the dialysis medium kept stationary but removed and replaced every 3 hours during the 9-hour test. Thus, 1,764 liters of water and gold were used as the dialysis medium, and 0.12 liters of dialysate was dialyzed. This ratio is 14
7, indicating that 147 volumes of dialysis medium were used per volume of dialysed fluid. The same equipment was used in the second and third tests with both continuous turbulent and continuous laminar flow conditions of the dialysis medium through the dialysis cell 10. In both tests, each 5m
Q of l, cellophane dialysis bag containing 75M copper sulfate 46
Dialysis was carried out against a total volume of 34.51 liters of water for 9 hours (total volume of fluid to be dialyzed: 0.21). In both tests, the ratio of dialysis medium to dialysed fluid was 150, which was essentially the same as in conventional static dialysis.
試験の結果透析袋中の残留液の硫酸銅含量を分析して次
の結果を得た。As a result of the test, the copper sulfate content of the residual liquid in the dialysis bag was analyzed and the following results were obtained.
１ バッチ １．８７ ４５００２
乱 流 ３．５９
２１００３ 層流 ０．９０ ８４００希釈係数Ｒに関して層流は従来のバッチ方式で可能な効
率の約２倍となることは明らかである。1 batch 1.87 45002
Turbulence 3.59
21003 Laminar Flow 0.90 8400 It is clear that with respect to the dilution factor R, laminar flow is approximately twice as efficient as possible in conventional batch mode.
必要とする透析媒質（水）３６の容量を減少する為のこ
の増加効率の応用は上記３試験に対応する他の試験で例
証した。その場合層流によって使用した水量は２０１に
減らし透析袋中の量を８７倍としかつ時間を２４時間に
増加した。前どおり硫酸鋼溶波谷５ｍｌを含む透析袋４
６個を用いた場合０、７５Ｍ硫酸銅溶液の濃度は０．４
７Ｘ １０−’ Ｍに減少した。The application of this increased efficiency to reduce the volume of dialysis medium (water) 36 required was illustrated in other tests corresponding to the three tests above. In that case, the amount of water used by laminar flow was reduced to 201 times, the amount in the dialysis bag was increased by 87 times, and the time was increased to 24 hours. As before, 4 dialysis bags containing 5ml of sulfuric acid steel
When using 6 pieces, the concentration of 0.75M copper sulfate solution is 0.4
It was reduced to 7X 10-'M.
これは希釈係数１６．０００又は大量の透析水を使って
パッチ操作から得た係数の約４倍に相当する。This corresponds to a dilution factor of 16.000 or about 4 times the factor obtained from patch operation using large volumes of dialysis water.
この様に透析されるべき液を操作中連続層シん中に保っ
た透析媒質中に浸漬した半透膜中に入れておく透析方法
は効率において実質的に改苦されろことは明らかであり
、この方法は次の１又は２以上の場合に使用して有利で
ある：１１１ 半透膜内に入れた透析可能成分を更に完全に
除去したい場合；（２）一定純度を得るに要する時間を短縮したい場合；（３） 要する透析媒質の量を減少したい場合：（４
） 透析を行うに要する装置を単純化したい場合；（５）透析装置に要する場所を小さくしたい場合；（６
）一定積製を行う手間を省略したい場き。It is clear that a dialysis process in which the fluid to be dialysed is placed in a semipermeable membrane immersed in a dialysis medium kept in a continuous bed during operation would suffer substantially in efficiency. , this method is advantageously used in one or more of the following cases: 111 When it is desired to more completely remove the dialyzable component contained within the semipermeable membrane; (2) when the time required to obtain a constant purity is If you want to shorten the time; (3) If you want to reduce the amount of dialysis medium required: (4
) When you want to simplify the equipment required for dialysis; (5) When you want to reduce the space required for the dialysis equipment; (6)
) When you want to omit the hassle of making a fixed volume.
図■・は本発明の透析容器の側車面図である。図■は図Ｘの腺２−２にそってとった断面図である。図■は図Ｘの腺３−３にそってとった断面図である。図■は本発明の透析容器に使用する支持枠の側面図であ
る。図Ｖは本発明の透析容器に使用する支持枠の平面図であ
る。図■と■は本発明の透析容器に使用する支持枠の両端立
直図である。図■は本発明の透析容器の入口端立面図である。図■は本発明の透析容器の出口端立直図である。図Ｘは本発明の透析容器の平面図である。図ＸＩは本発明の透析容器内に支持枠の配置を示す分解
配列透視図である。１０・・・・・透析槽、 １５．１６・・・・・・槽の
両端、 ２０．２１・・・・・・槽の両側面、 ２５・
・・・・・槽の底、 ４０・・・・・・入口孔、 ４５
・・・・・・溢流口、 ５０・・・・・・水路、 ５１
・・・・・・空気孔、 ５５・・・・・・出口孔、 ６
０・・・・隔板、 ６５・・・・・・区画室、 ７０・
・・・透析袋、 ８０・・・・・支持枠、 １１５゜１
２０、１２５・・・・・・検出器。ＲＧＵＥＥ １７手続補正書（方式）％式％１事件の表示昭和６２年特許願第１９２７６９号２、発明の名称透析法３補正をする者事件との関係 特許出願人名称 ブリストル マイヤーズ カンパニー４、代理人氏名 弁理士 （６３２３） 川 瀬 良 治′５、
補正命令の日付昭和６３年１月２６日６、補正の対象７、補正の内容（１）明細書１６頁１７行〜１７頁１２行の全文を次の
とおり補正する。「 図１は本発明の透析容器の倒立面図である。図２は図１０の線２−２にそってとった断面図である。図３は図１０の＄３−３にそってとった断面図である。図４は本発明の透析容器に使用する支持枠の側面図であ
る。図５は本発明の透析容器に使用する支持枠の平面図であ
る。図６と７：ま本発明の透析容器に使用する支持枠の両端
立面図である。図８は本発明の透析容器の入口端立面図である。図９は本発明の透析容器の出口端室面図である。図１０１ま本発明の透析容器の平面図である。図１１は本発明の透析容器内に支持枠の配置を示す分解
配列透視図である。」（２） 別紙のとおり図面の図番号を補正する。Figure ■ is a side view of the dialysis container of the present invention. Figure ■ is a sectional view taken along gland 2-2 in Figure X. Figure ■ is a sectional view taken along gland 3-3 in Figure X. Figure 3 is a side view of the support frame used in the dialysis container of the present invention. Figure V is a plan view of the support frame used in the dialysis container of the present invention. Figures 1 and 2 are vertical views of both ends of the support frame used in the dialysis container of the present invention. Figure 3 is an elevational view of the inlet end of the dialysis container of the present invention. Figure 3 is an upright view of the outlet end of the dialysis container of the present invention. Figure X is a plan view of the dialysis container of the present invention. FIG. XI is an exploded array perspective view showing the placement of a support frame within a dialysis container of the present invention. 10...Dialysis tank, 15.16...Both ends of the tank, 20.21...Both sides of the tank, 25.
... Bottom of tank, 40 ... Inlet hole, 45
...Overflow port, 50 ... Waterway, 51
...Air hole, 55...Outlet hole, 6
0... Partition plate, 65... Compartment, 70.
...Dialysis bag, 80...Support frame, 115゜1
20, 125...Detector. RGUEE 17 Procedural amendment (method) % formula % 1 Display of the case 1986 Patent Application No. 192769 2 Name of the invention Dialysis method 3 Relationship with the person making the amendment Name of the patent applicant Bristol Myers Company 4, Agent Name Patent Attorney (6323) Ryoji Kawase'5,
Date of amendment order: January 26, 1986 6. Subject of amendment 7: Contents of amendment (1) The entire text of page 16, line 17 to page 17, line 12 of the specification is amended as follows. 1 is an inverted top view of the dialysis container of the present invention. FIG. 2 is a cross-sectional view taken along line 2-2 in FIG. 10. FIG. 3 is a cross-sectional view taken along line 2-2 in FIG. FIG. 4 is a side view of the support frame used in the dialysis container of the present invention. FIG. 5 is a plan view of the support frame used in the dialysis container of the present invention. FIG. 8 is an elevational view of both ends of a support frame used in the dialysis container of the present invention. FIG. 8 is an elevational view of the inlet end of the dialysis container of the present invention. FIG. 9 is a chamber view of the outlet end of the dialysis container of the present invention. Fig. 101 is a plan view of the dialysis container of the present invention. Fig. 11 is an exploded arrangement perspective view showing the arrangement of the support frame within the dialysis container of the present invention. Correct.
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US55078975A | 1975-02-18 | 1975-02-18 | |
| US550789 | 1975-02-18 |
| Publication Number | Publication Date |
|---|---|
| JPS63185408Atrue JPS63185408A (en) | 1988-08-01 |
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP51016074AGrantedJPS51106684A (en) | 1975-02-18 | 1976-02-18 | Soryutosekihooyobisonosochi |
| JP62192769APendingJPS63185408A (en) | 1975-02-18 | 1987-08-03 | Dialytic method |
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP51016074AGrantedJPS51106684A (en) | 1975-02-18 | 1976-02-18 | Soryutosekihooyobisonosochi |
| Country | Link |
|---|---|
| JP (2) | JPS51106684A (en) |
| FR (1) | FR2301282A1 (en) |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003534547A (en)* | 2000-05-25 | 2003-11-18 | ジーン、バイオ‐アプリケーション、リミテッド | Processing chamber with opening for pipette access |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60119901U (en)* | 1984-01-23 | 1985-08-13 | 株式会社トクヤマ | Diffusion dialysis device |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB492609A (en)* | 1936-04-29 | 1938-09-22 | Ig Farbenindustrie Ag | Apparatus for dialysing liquids |
| US2720879A (en)* | 1950-08-01 | 1955-10-18 | Gasca Albin | Dialysis apparatus |
| US3108066A (en)* | 1959-10-02 | 1963-10-22 | Chantooni Arsen Miran | Means for processing fluids |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003534547A (en)* | 2000-05-25 | 2003-11-18 | ジーン、バイオ‐アプリケーション、リミテッド | Processing chamber with opening for pipette access |
| Publication number | Publication date |
|---|---|
| FR2301282B1 (en) | 1979-04-06 |
| JPS6327043B2 (en) | 1988-06-01 |
| JPS51106684A (en) | 1976-09-21 |
| FR2301282A1 (en) | 1976-09-17 |
| Publication | Publication Date | Title |
|---|---|---|
| US3211645A (en) | Method and apparatus for filtering sanguineous liquid streams | |
| Gros et al. | The diffusion of carbon dioxide in erythrocytes and hemoglobin solutions | |
| EP0402611B1 (en) | Process for performing a dialysis operation using a magnetic weighted clamp | |
| US4844871A (en) | Method of determining the partial pressure of gases in blood and an apparatus for performing the method | |
| US4284491A (en) | Apparatus for electrophoresis | |
| US3855111A (en) | Electrophoresis apparatus | |
| US4844097A (en) | Apparatus and method for testing liquids | |
| US3616456A (en) | Device for isoelectric separation of ampholytes | |
| EP0018375A1 (en) | DEVICE AND METHOD FOR CONTINUOUS FLOW OF ISOELECTRIC FOCUSING. | |
| US3888758A (en) | Apparatus for large scale gel electrophoresis | |
| US4911816A (en) | Process for conducting electrophoresis and transfer | |
| JPH10507960A (en) | Apparatus and method for sample dialysis | |
| EP0489602A2 (en) | Filtration arrangement | |
| JPS63185408A (en) | Dialytic method | |
| EP0300924B1 (en) | Process for conducting electrophoresis and transfer | |
| US3827304A (en) | Sample handling method | |
| US3847785A (en) | Electrophoresis aparatus | |
| Chalmers et al. | Evaluation of a new thin film tonometer | |
| EP0190188A1 (en) | Cell growth | |
| Winsten et al. | Large-volume continuous-flow electrophoresis of serum proteins with glass microbeads | |
| US11249056B1 (en) | Dialysis based invitro drug release study method | |
| JPS6049865B2 (en) | Method and apparatus for determining cell penetration resistance of cell-containing samples | |
| CN223010246U (en) | A dialysis concentration device in a new purification process of red blood cell membrane monoclonal antibody | |
| JPH0247960Y2 (en) | ||
| JPS5953827B2 (en) | Automatic sampling device and method |