IL32652A - Fluid processing apparatus and method - Google Patents

Description

WW ID PROCESSING APPABATUS AND METHOD This invention is concerned with apparatus and method for performing various processes with fluids as, for example, in analytical or preparative chemistry and in which the fluids being processed are divided into isolated units and are processed while confined in a conduit.

The prior art concerned with process methods and apparatus of the kind with which the invention is concerned broadly divides itself into "batch processing" and "continuous processing". An example of batch processing is found in the practice of putting separate samples, e.g. blood, urine, water, gas or any fluid sample, in separate containers and treating such samples with separate portions of reagents while the samples are maintained out of contact with each other during processing. In a known form of continuous processing, the samples separated by air bubbles flow in a stream in a conduit or tube and are introduced in a predetermined sequence. The air bubbles which form part of the stream greatly inhibit longitudinal mixing. For this reason, they appear to wash the , walls of the conduit or tube as they move and such action is, of course, of great assistance in maintaining the samples as discrete entities. In both batch and continuous processing various approaches have been taken in the prior art with respect to adding and subtracting from the samples and for treating and analyzing the samples including steps such as heating, cooling, dialysis, mixing, or colorimetry.

Both batch and continuous apparatus and methods as presently developed inherently exhibit both desirable and undesirable characteristics. For example, the batch process insures absolute isolation between samples, whereas in a continuous process, isolation is not absolute and, in fact, difi- an advantage in that the process steps are generally independent of time between steps, whereas with a continuous process, if the flow rate changes or if processing is actually stopped, the results being sought are directly affected. The methods and apparatus employed with the continuous process, on the other hand, offer an advantage in that processing can be completed very rapidly on large numbers of samples. Another advantage in the continuous type processing is that analysis operations may be performed employing incomplete reactions since timing is an inherent part of the process whereas with batch processing it is generally essential for reactions to be complete before the analysis work can be properly undertaken or else time must be controlled as an additional factor. Steps such as filtration and addition are discontinuous in the case of batch processing but are necessarily continuous in the case of continuous processing. Furthermore, the batch and continuous processing are different in that in batch processing the samples move in the same or different receptacles to the various processing sites whereas in continuous processing the samples and related materials move but their container, i.e. the conduit in which the sample, stream is flowing, remains stationary. While individual samples may be processed in batch processes without disturbing adjoining samples, there is no known practical way in continuous processes, for example, to add to or subtract from selected samples forming part of a continuous stream without disturbing adjoining samples. While. other comparisons might be made, it is believed the. above _is .-sufficient to appreciate the significance of the present invention.

According to the present invention, the better features of both batch and continuous processing can be obtained first conduit for containing fluid, said conduit having opposed portions capable of retractable movement relative to each other; a plurality of releasable, hydraulic sealers spaced apart across said conduit to form hydraulically isolated chambers and each of said sealers being movable along said conduit; and one or more second conduit communicating with and located at selected points along said first conduit for selectively admitting or removing fluid from said chambers.

The fundamental character of the invention depends upon employment of a liquid container which is preferably in the form of an elongated tube or conduit, and which is further characterized by having a substantial portion of the wall of the conduit formed of a material which can be deformed by movement lateral to the longitudinal axis of the conduit to form a series of spaced hydraulic seals internally of the conduit and thereby form the conduit itself into a series of hydraulically isolated chambers Essentially, the invention is directed to establishing and maintaining a plurality of spaced deformation or pressure points in a conduit such as a flexible plastic tube having a resilient or retractable type wall such that at each pressure point there is a substantially perfect hydraulic seal to prevent any transfer of liquid through the seal; a sufficient number of the pressure points are established at predetermined intervals along the length of the conduit in which the liquid is to be processed to insure that at all stages of processing in such length the seals remain effective and such length is substantially continuously divided at all times into a series of voids or chambers capable of confining increments of liquid such that the increment of liquid in each void or chamber is held hydraul- a l is l ed fr m ll ther incremen s of li uids the fluid maintained hydraulically isolated and are caused to move along the tube or relative to the tube by reason of the pressure points being maintained and moved relative to the tube. That is, while the invention can be operated on a continuous basis in the sense of the increments of liquid moving in a substantially uninterrupted sequence along the length of tubing used in processing the liquid, the liquid is processed in a batch-like manner in that the liquid is introduced and transported as increments and these increments do not form part of a stream as in prior art continuous processes.

Another aspect of the present invention is directed to employment of the just described hydraulically isolated chambers or voids for steps or stages of processing of liquids confined in such chambers. By "processing" at this point in the description is meant the performance of any typical process step such as adding or subtracting from the liquid, observing or measuring, or filtering. Processing according to the invention is effected on the liquids while the liquids are confined in the mentioned chambers. That is, the hydraulically isolated chambers are formed, the liquids are admitted to the chambers, the chambers are maintained in existence throughout processing of such liquids, and even though a chamber, in effect, moves along the length of conduit or tube used in processing such liquid, the liquid in each chamber is maintained in hydraulic isolation from the liquid in all other chambers. Furthermore, according to the invention the chambers are treated as batch type containers in that liquids in each chamber are admitted, withdrawn and reacted or otherwise treated independently of what operations are performed on liquids in any other chamber.

Figure 1 is a perspective, cut away, view of an apparatus embodying the invention; Figure 2 is a perspective view of another apparatus which may be cylindrical but which for illustration is shown laid out; Figure 3 is a partial section view illustrating employment of a resilient roller; Figure 4 is a partial section view illustrating employment of a rigid roller; Figures 5 through 10 illustrate schematically various stages of movement of a unit of fluid relative to the conduit; Figure 11 illustrates a type of internal seal that may be employed for draining the conduit at a location; Figure 12 illustrates a type of permanent internal seal that may be employed to effect division of units of fluid; Figure 12A illustrates a type of internal sealing that may be employed as a network to effect both division and recom-bining of units of fluid; Figure 13 illustrates how a chamber may be filled with a known quantity of fluid at a station; Figure 14 illustrates how a constant volume of fluid may be introduced independent of specific timing; Figure 15 illustrates how a unit or sample of fluid may be diluted to a known volume; Figure 16 illustrates an auxiliary roller to accelerate mixing of fluid in a chamber; Figure 17 illustrates use of permanent internal seals to effect mixing; Figure 18 and Figure 19 illustrate in elevation and lan res ectivel em lo ment of an internal membrane and er Figure 20 illustrates employment of electrodes for pH measurements; Figure 21 illustrates employment of an optical cuvet with the apparatus of the invention; Figure 22 illustrates a comprehensive system following the invention.

Referring to the drawings, Figure 1 illustrates somewhat schematically one basic form of the invention and in which represents a cylindrical body of rigid material such as metal, hard plastic or the like. A flexible tube 26 which may be plastic or the like is secured to the inside wall 28 of the body 25. Tube 26 is a continuous tube of uniform internal diameter and the length of tube 26 is assumed to represent the length of tube required to complete some desired process such as determining the hemoglobin content of blood. A tube 30 mounts in the wall of the body and is arranged to communicate with tube 26 such that a liquid source such as a source of blood generally represented at 31, may be admitted to tube 26. Another tube 32 which is peripherally spaced from tube 26 is also mounted in the wall of body 25 and like tube 30 communicates with tube 26 such that a source of reagents or the like designated generally at 33 may be communicated to the liquid in tube 26 or the liquid in tube 26 communicated to the reagent source 33 dependent on the nature of the process. An additional tube 34 is mounted in the wall of body 25 and serves the purpose of removing the liquid after completion of processing as well as providing a means for admitting washing solutions or the like as generally designated at 35. Valves 29 may be employed to block the tubes 30, 32, 34 as desired. provided by the apparatus which includes the three rollers 40, 41, 42 mounted on the respective arms 43 (not shown), 44 and 45. Arms 43, 44 and 45 are spring loaded as schematically represented by the springs 46 which are selected so that they will provide sufficient tension to effect substantially perfect hydraulic seals at those points where rollers 40, 41 and 42 compress the tube 26.

The roller structure is powered through a shaft 50 which is connected to a suitable source of low speed power, not shown. For example, assuming Figure 1 is essentially full scale such a source of power might operate shaft 50 at two to three revolutions per minute. As shaft 50 turns it can be seen that the hydraulic seals indicated at 51, 52 and 53 will progressively move along the length of tube 26 while maintaining their relative intervals or spacing fixed. Thus a "chamber" will be formed between rollers 41 and 42, a second chamber will appear between rollers 42 and 43, and a third chamber will appear between rollers 43 and 41 and each of these chambers will be hydraulically isolated one from the other by reason of the hydraulic seals established and continuously maintained by rollers 41, 42 and 43 and irrespective of whether or not rollers 41, 42 and 43 are moving. That is, unlike prior art continuous processes, the present invention apparatus and methods do not depend on continuous motion or flow of the liquid to maintain segmentation of the liquids into isolated units since shaft 50, for example, or its counterpart in other embodiments of the invention may be physically stopped and this will not affect the presence of the chambers which cause the various units of liquid to be hydraulically isolated. In the air bubble type of seg or alter their dynamic relationship, and undesirable longitudinal mixing is experienced.

As shaft 50 slowly rotates, it can be seen that the three chambers which are formed within the tube 26 between each pair of rollers and which gradually progress around the length of the tube remain hydraulically isolated one from the other such that fluids can be admitted, removed or treated in one chamber without disturbing the remaining chambers and even while other operations are being performed in the other chambers.

Furthermore, all such operations may be conducted on a continuous basis in the sense that shaft 50 may be rotated relatively slowly which enables each chamber to remain isolated while it progressively changes position and for processing in such chamber to be completed during the course of such movement. At three revolutions per minute, for example, nine samples can be completely processed each minute.

Another somewhat generalized explanation of the invention is illustrated in Figure 2 in which the basis structure is developed as a planar rather than a cylindrical structure to show that the invention may be embodied in many of various structural forms. In Figure 2, the body 60 corresponds to the body 25 of Figure 1 and the rollers 61, 62, 63, 64, 65, 66 and 67 correspond to the rollers 40, 41 and 42. The numeral 70 designates a sheet of material which may be flexible or relatively inflexible as for example rubber, or any of various plastic sheet materials such as those sold under the trademarks Tygon, Teflon or the like. Sheet 70 is secured to the edges of body member 60 by means of a suitable adhesive applied along the edge adhesive lines 71, 72 such that the space or void between itself to being formed from any of various materials such as metal, any of the rigid plastics, hard rubber or the like.

Likewise rollers 61 through 67 may be formed of various materials such as metal, hard rubber or the like. As indicated in Figures 3 and 4, the specific character of the body 60 and rollers 61 through 67 may vary in having the body represented by 60' in Figure 3 of a rigid material, the sheet represented by 70' of a non-elastic material and the rollers indicated by 61' of a resilient material. As illustrated in Figure 4, the base 60" may be of a resilient material, the sheet 70" of a non-elastic material and the roller 61" of a rigid material, the purpose being to establish and maintain substantially perfect hydraulic seals at the various points of contact indicated at 61a, 62a, 63a, 64a, 65a, 66a and 67a.

To further illustrate the versatility of the invention, it will be noted that liquid inlet and outlet tubes are indicated at 75, 76, 77, 78, 79 and 80 each of which may be controlled by a valve 81. In operation, rollers 61 through 67 generally represent means for compressing or deforming the conduit path established by body member 60 and an envelope or sheet 70 such that substantially perfect hydraulic seals are established and maintained at each of the points 61a through 67a as such points move progressively along the length of such conduit path. Thus, as in Figure 1, there is established in Figure 2 between each pair of rollers such as rollers 61 and 62 a chamber or void at 85 which is and remains hydraulically isolated from all of the remaining chambers indicated at 86, 87, 88, 89 and 90. Assuming body member 60 and sheet 70 to be fixed, as rollers 61 through 67 move progressively at a relav: contents also progressively move due to the progressive movement of the hydraulic seals established at 61a through 67a. Now as this progressive or relative movement between body 60 and rollers 61 through 67 is taking place, whatever liquids are involved in the particular process may be admitted, withdrawn, mixed or otherwise processed in the various chambers by means of the tubes 75 through 80 and such operations may be performed in chamber 85, for example, completely independent of operations performed in, say, chamber 86. Taking chamber 85 as a further example, it can be seen that when chamber 85 is at the position shown in Figure 2, liquids can be admitted, withdrawn or mixed by means of tube 75 without disturbing the contents of any of the remaining chambers. As chamber 85 progressively moves and assumes the position which chamber 86 occupies in Figure 2, the contents of chamber 85 can again be operated on through tube 76 and again this can be done independently of whatever operations are being performed in any of the remaining chambers.

The movement of an individual chamber formation or void is further illustrated in Figures 5 through 10 in which what is regarded as chamber 35 is shown in various progressive stages of movement. It will, of course, be understood that in the embodiment of the invention being explained in reference to Figures 2 and Figures 5 through 10 the sheet or envelope 70 is integrally secured to the body member 60 and both sheet 70 and body 60 remain stationary while rollers 61 through 67 are progressively moved by means not shown. Thus, the word "chamber" is intended to mean the space established between a particular pair of rollers and, as such pair of rollers moves, the space between the rollers is necessarily moved or relocated even thou h the sheet 70 does not move conse uentl an li uid pair of rollers will be progressively moved as the chamber in which it is confined moves. Comparing Figures 5 through 10, it will be seen that chamber 85 in Figure 5 is in communication with tube 75, in Figure 6 with tube 76, in Figure 7 with tube 77, in Figure 8 with tube 78, in Figure 9 with tube 79, in Figure 10 with tube 80. Such action enables chamber 85 to successively come into communication with the tubes 75 through 80 and at each undergo any desired type of fluid exchange involved in the particular process being followed. The liquid that is confined in chamber 85 in Figure 5 could be, say, liquid X and to this a new liquid Y could be admitted in the position of, say, Figure 7. It should also be understood that chambers ahead and behind chamber 85 could at any time contain the same or dissimilar units of fluid.

Other aspects of the invention will be discussed with reference to generalized diagrams. Figure 11 is a planar view in which the rollers used for developing the hydraulic seals are indicated at 99, 91, 92 and 93. The sheet 94 corresponds to the sheet 70 and the lines of adhesion of sheet 94 to the body member which is hidden from view are represented at 95, 96, these edge lines of adhesion corresponding to adhesions 71, 72 in Figure 2. In Figure 11, a further area or line of adhesion is indicated at 98 and this represents a permanent seal which may be developed either mechanically or by an appropriate adhesive so as to provide a permanent hydraulic seal just ahead of an outlet tube 100. That is, Figure 11 illustrates a positive means by which every chamber can be emptied through outlet 100. For example, assuming roller 92 is moving in the direction of the arrow, any fluid confined in the space between Another requirement which is faced in processing apparatus is that of being able to divide and combine samples and the manner in which the invention lends itself to this requirement is illustrated by Figures 12 and 12A. In Figures 12 and 12A the edge adhesions 105, 106 correspond to the edge adhesions 71, 72. For purpose of splitting the fluid as it is moved, an additional bent adhesion line is employed as indicated at 107 such that as the rollers progress the fluid is divided and forced to pass on either side of line 107 as indicated by the arrows. By providing an outlet as indicated at 109 it can also be seen that some predetermined portion of the liquid can be withdrawn from each chamber as such chamber arrives at and moves past line 107 and outlet 109. In Figure 12A the adhesion lines 104 and 108 illustrate triple dividing by forming multiple sub-chambers, followed by recombining of the contents of two sub-chambers and followed by recombining of the contents of all sub-chambers . This same concept may be utilized in establishing parallel or series or various other flow networks as is sometimes found useful in analytical and preparative chemistry.

While the invention lends itself to various means of introducing liquids to the chambers, Figure 13 illustrates an arrangement wherein the rollers are assumed to be moving at a constant speed past an inlet tube 110 which is connected to a constant volume pump 111 which pumps from the sample source 112. Such an arrangement provides continuous introduction of the samples in equal volume per chamber which is equivalent to the conventional continuous processing apparatus and method but with the important exception that with the present invention there is zero interaction and zero longitudinal mixing between In Figure 14, the volume of sample is controlled by an outside device, a syringe being indicated at 115 as an example, and which is connected to a barrel valve 116 which can be turned to draw from the sample 112 or force fluid into the inlet tube 117. Of particular significance here is that the sample can be injected without regard to timing as long as the port 118 is between the rollers as, for example, rollers 119, 150 and such injection can be rapid or slow. In fact, as previously mentioned, it has been .found that....the. rollers can actually be stopped or operated by a program of indexing without introduing any intermixing between samples. This advantage gives the apparatus and methods of the invention the characteristic of batch processing but with the ability to operate as a continuous or semi-continuous process. Precise procedures according to the Figure 14 will vary with specific processes. For example, if desired each sample injection can be followed by injection of some known amount of wash solution such as water or air or a mixture of these in order to clear out the dead space in the injection port Reagents or the like can also, of course, be added and removed by the techniques previously described.

Diluting to a known fixed volume according to the invention may be practiced in various ways. Figure 15, for example, illustrates a vacuum mold 120 which can be lowered from a raised position indicated at 120' to engage the sheet or envelope 122, corresponding to sheet 70 in Figure 2, so as to form the chamber below mold 120 into a void of known volume. That is;, mold 120 is made with a known volume and shape and its engagement with the envelope 122 is arranged such that the chamber as indicated at 123 is established with a predetermined volume. In this con to a known fixed volume. Other means may be employed for the same purpose such as relating volume to some predetermined pressure which has been calibrated to a particular volume. It should also be noted here that Figure 15 illustrates one means of accomplishing a pipetting type process operation in that if a known volume of liquid is in chamber 123, for example, the bringing of the volume of liquid in chamber 123 to some new known volume is effectively adding a volume equal to the difference.

Lateral mixing of process samples being transported longitudinally in a tube or conduit often is desirable and the invention lends itself to various ways of mixing. Figure 16 illustrates, for example, a mechanical form of mixing and in which roller 130 represents a roller of somewhat shorter length than the other rollers indicated at 131, 132, 133 and 134. The rollers 131, 132, 133 and 134 move in a common direction as indicated by the arrow 135. Roller 130 is mounted on means, not shown but whose general structure will be apparent to those skilled in the art, which causes it to move back and forth relative to selected pairs of rollers which causes the liquid confined in the chamber established between, for example, rollers 132 and 133 to be squirted through the narrow area indicated at 136 between the end of roller 130 and the adhesion line 137.

Roller 130 lifts by means not shown and returns to its mixing position as the next chamber reaches the mixing position.

Mixing may also be effected by use of adhesion lines which disturb the movement of the liquid in the chambers sufficient to cause mixing. An example of this is illustrated in Figure 17 in which the stippled areas 140, 141 represent areas in which the sheet or envelope corresponding to sheet 70 in formed by the rollers 143 and as the rollers and the chambers progressively move in the direction of the arrow shown in Figure 17, the fluid confined in the chambers will be caused to move back and forth and thus mixing will be effected, as with the structure of Figure 16, by turbulent flow through the narrow passages .

The invention also readily lends itself to process steps of heating and cooling. While not shown, it will be obvious to those skilled in the art that heating of liquids confined in the chambers may be accomplished by bringing the chambers proximate a source of controlled heat or, if cooling is desired, by bringing the chambers proximate a coolant liquid or other heat extraction means. The invention also readily adapts itself to the step of volatilization in that the methods and apparatus of the invention are able to handle gases as well as liquids and therefore any means of volatilization of one or more constituents in a chamber can be used such as addition of a reagent which frees a gas, e.g. carbon dioxide, or heating to vaporize.

Employment of the invention for separation of fluids may be carried out in various ways. For example, if the apparatu of Figure 2 is oriented in a vertical plane and the separation step involves separation of gases and liquids, it can be seen that the gases can be extracted from the top of chambers by mounting certain of the tubes on top of the conduit. While not shown, by adopting conical gasometry for the structure employed to practice the invention so that the body member takes the form of an inverted cone and the rollers or other compression devices are mounted on the wall of the cone, centrifuging may be and is powered to rotate around its principal axis, rapid rotation of the entire apparatus will cause two dissimilar liquids to separate with one being forced to one edge and the other to the opposite edge of the conduit. Solvent extraction, another typical process step, is also readily practiced by use of the invention since reagents may be added, mixed and separation accomplished by the means already described.

The process step of dialysis is one of the considerable importance and may be effected in various ways within the scope of the invention. Figures 18 and 19 illustrate somewhat schematically a method and apparatus by which crystalloids may be transferred across a membrane internally of a chamber. In Figure 18 there is shown a schematic view in elevation of a dialysis arrangement and Figure 19 shows the same in a plan view. This arrangement employs an outer sheet 160 corresponding to sheet 70 of Figure 2, and an inner permeable membrane sheet 161. The X cross hatching illustrates where both sheets are adhered to the body member 162, the slanted line hatching indicates where only the outer sheet 160 is adhered to the body member 162, and the dashed hatching indicates where only the inner sheet 161 is adhered to the body member 162. A tube 164 is adapted to admit the recipient fluid and a tube 165 admits the donor fluid. A tube 166 is adapted to discharge the donor fluid. As illustrated by Figures 18 and 19, as each pair of rollers, such as rollers 168, 169, move in the direction of the arrows shown in Figures 18 and 19 and arrive over tube 164, the recipient fluid is admitted to the chamber which is formed solely by the outer sheet or envelope 160 between rollers 168, 169. Continuing to use rollers 168 and 169 for reference, At this stage, the donor fluid is admitted through tube 165 and is confined in the chamber formed by the inner sheet 161. That is, by securing the two sheets 160 and 161 along the lines of adhesion indicated in Figures 18 and 19, it becomes possible to effectively have two chambers between each pair of rollers.

Thus, in Figure 18, chamber 170 which is formed between sheets 160 and 161 and above tube 165 is shown holding the recipient fluid and chamber 171 which is formed between sheet 161 and the body member 162 and above tube 165 is shown holding the donor fluid. Now, as the rollers 168, 169 move from left to right in Figures 18 and 19, it can be seen that dialysis can be effected between the donor fluid and the recipient fluid and the donor fluid will be forced out of tube 166 as the rollers move past tube 166. It may be noted that while adhesion has been mentioned as a securing means for the lines of adhesion such as, for example, those indicated in X cross hatching in Figure 19, a liquid proof zipper type construction or similar releasable securing means may be employed to facilitate washing the various components. That is, selected lines of adhesion may be affected in some cases by mechanical releasable securing means rather than by using permanent adhesive materials on such lines of adhesion .

The application of pressure is sometimes required and in this regard it is noted that the apparatus previously discussed may be operated under pressure in a pressure chamber if desired or portions of the apparatus may be submerged in a heavy liquid such as mercury to obtain desired amounts of pressure. With regard to observation of the liquids confined in the chambers, pH electrodes or electrodes for other purposes may be in Techniques of potentimetric, conductimetric, polargraphic and other measurements are readily applicable.

Optical observations such as colorimetry, spectrophotometry, florimetry, turbidimetry and nephelometry are important in analytical chemistry and in processing and an explanation will now be made of the application of the invention to such observations. Where qualitative information only is desired, as for example, in detecting, by the color, the end point of a titration in a given amount of liquid confined in a particular chamber, observation may simply be made by utilizing a transparent sheet as the conduit envelope. Figure 21 illustrates an optical cuvet and is assumed to show a sectional view taken through the body member and the sheet or envelope. In this case the sheet 180 is further assumed to contain a liquid of interest for optical observation and movement of the chambers is out of the page toward the reader. Built into the body member 181 is a syringe like structure 182 such that when the chamber holding the liquid of interest is over structure 182, the liquid of interest can be drawn down into the light path indicated between the light source 183 and the photocell 184. After the observation has been made the fluid is then forced back into the chamber by means of structure 182 and structure 182 is held in its raised position until it is desired to draw other liquids for optical observation. Two separate cells may be arranged to examine at two wave lengths simultaneously or a blank or standard liquid may be examined simultaneously with some unknown liquid. It is also important to recognize that it is not necessary to stop movement of the chambers to perform the desired examinations. requirements. Of course, analytical and preparative procedures other than those referred to are used but it is believed that those skilled in the art will readily appreciate the modifications required to practice any procedure which was not discussed. Reference will now be made to a specific procedure and its application to the invention, namely, that of determining the hemoglobin content of blood. In this procedure, whole blood is diluted and laked (cells broken) with a 0,37o solution of the tetrasodium salt of EDTA (ethylenediamine tetracetic acid) and oxygenated by exposure to air. The oxyhemoglobin is measured by its absorbance at 540 m ^ . In the actual procedure, 5.0 li li milliters of EDTA are measured into a cuvet. 0.020 Milliners of whole blood is then pipetted in after which the solution is stoppered and shaken several times to mix the reagents together and with air. The absorbance is measured at 540 ti xin 1 centimeter path length cuvet. The grams of hemoglobin per 100 milliliters of blood is equal to the result of multiplying the absorbance by a known constant.

The same procedure when performed according to the invention is explained in reference to Figure 22 which shows in a planar diagram an apparatus which could actually partake of a cylinder construction as in Figure 1. In Figure 22, the sheet or envelope 190 is assumed to be cylindrical and have five chamber spaces two centimeters by two centimeters each, the diameter of the cylinder forming the envelope being 3.2 centimeters. As shown in Figure 22, air in the required quantity is injected in tube 191 and the EDTA solution is injected in tube 192. The blood sample is injected in tube 193 and mixing is effected by the mixing roller 194. During the period of time the sample is discharged through tube 196. While there is no inherent limit to the rate of operation, a typical rate might be 10 samples per minute.

Among other advantages not previously mentioned, the invention does not require employment of a resilient, normally open, constant diameter tube as in prior art air bubble type systems, for example. While the "chambers" have been indicated for purposes of illustration as bulged areas as, for example, in Figures 5 through 10, a typical "chamber" according to the invention will normally contain either some measured volume of liquid or else will be completely empty and in a flat state devoid of air as, for example, shown in respect to chamber 198 in Figure 14. Thus, the invention, unlike the prior art apparatus, requires neither a resilient wall nor one which is normally open. Further, the diameter of the tube or conduit employed in practicing the invention can vary in size and does not need to maintain or return to some constant value. In fact, the size of the conduit according to the invention will vary according to what is put into the conduit as seen by way of example in Figure 14.

Claims (5)

1. WHAT IS CLAIMED IS : THE EMBODIMENTS OF THE INVENTION IN WIIIGII AN EXGLUSIVE PROPERTY OR PRIVILEGE ID GLAIMED ARE DEFINED AO FOLLOWD:1 1. Apparatus for processing of fluid in units comprising a first conduit for containing fluid, said conduit a flexible nail having /opp sed-4^ie-frirOft3--ea a ^ .rollers a plurality of releasable¾/ hydrauH-c—¾ea¾ s- spaced apart across said conduit to form hydraulically isolated rollers chambers; and each of said s-ea£e¾?e being movable along said conduit; and one or more second conduit communicating with and located at selected points along said first conduit for selectively admitting or removing fluid from said chambers.
2. 2. Apparatus according to Claim 1 which comprises, in addition, means first conduit for performing unit handling and chemistry type processes upon the contents of selected said chambers independently of all other said chambers.
3. 3. Apparatus according to Claim 1 or Claim 2 wherein said first conduit is a continuous tube having a resiliently flexible wall and said tube is mounted on a cylindrical body.
4. 4. Apparatus according to Claim 3 wherein the rollers &eale¾?6 compress the wall of said tube and on said cylindrical rollers body, said -s-ea4.-i«g means rotate around the axis of the cylindrical body.
5. 5. Apparatus according to Claim 1 or Claim 2 wherein said first conduit comprises a body member having an impervious sheet member secured to said body member at the edges of said sheet . 6 —Apparatus according to an one of Claims 1 ta -5 whoroin tho coaloro oomprioo a plurality of epaood rollers adapted to compress said conrfnit. 6.?. Apparatus according to Claim 5 wherein said impervious sheet member is adhered to said body member at a selected location to provide a non-releasable hydraulic seal blocking at such location, and said second conduit communicates with said first conduit at such location, thereby enabling the rollers s-ee-lei* to force fluid out of each successive chamber arriving at said location. 7.8·. Apparatus according to Claim 5 wherein said impervious sheet member is adhered to said body member at a selected location and in a manner effective to divide the fluid contents of any chamber arriving at such location into a plurality of portions and further being effective to establish a permanent hydraulic seal blocking said path as to certain of said portions and continuing said path as to others of said portions and said second conduit communicates with said first conduit at such location in the path of said certain portions thereby enabling said sealers to cause the fluid contents of each said successive chamber to be divided and said certain portions to be forced out of such chamber at said location while said other portions are continued past said location. 8.9·. Apparatus according to any one of Claims 1 to 5 which includes, in addition a pump communicating with said second conduit and operative to provide known constant volumes of fluid. 9« H Apparatus according to Claim 1 comprising means located proximate said first conduit at a selected location and operative on said first conduit to form a selected said chamber into a chamber of predetermined volume and additional means communicating with said first conduit at said selected location enabling the fluid contents of said selected chamber to be diluted to said known volume. 10. t"t*. Apparatus according to Claim 1 including auxiliary mixing means comprising auxiliary releasable h¾«k5e¾4ie- roll s-e-a-l-eys- partially across said first conduit and between and rollers relative to the seals established by said seo cro thereby inducing flow through constricted areas and fluid mixing within each said chamber where so established. 11J*¾-. Apparatus according to Claim 5 including for purposes of dialysis an auxiliary permeable sheet member of length less than the length of the impervious sheet member and interposed between said impervious sheet member and said body member to form a subsidiary conduit within said first conduit, the ends of said permeable sheet member having its ends sealed to said body member and its edges sealed to the body member, and wherein said second conduit means includes first subsidiary conduit communicating with said first conduit for admission of recipient fluid within a portion of said first conduit not having said permeable sheet member, second subsidiary conduit communicating with said subsidiary conduit for admission of donor fluid to be confined between said permeable sheet member and said body member and third subsidiary conduit means communicating with said subsidiary conduit for discharge of said donor fluid, said rollers ■6-eale 6 being effective in cooperation with said permeable sheet member and subsidiary conduit means to effect dialysis between said donor and recipient fluids. 12.13, Apparatus according to Claim 1 including electrode arranged within said conduit at a selected location such that any fluid confined in a chamber passing such location is placed in electrical contact therewith thereby enabling electrical measurement of such fluid. 13· Apparatus according to Claim 5 wherein said body member includes a permanent chamber formed therein, means to draw said fluid into said permanent chamber and means located proximate said permanent chamber adapted to optically examine said fluid confined therein. 14. t5-. Apparatus according to Claim 1 including means for analyzing the contents of said chambers. 15.-16. Apparatus according to Claim 1 wherein at a selected location portions of said first conduit are sealed internally thereof and longitudinally in a manner effective to divide the fluid contents of any chamber arriving at such location into a plurality of chambers. l6»-i-7. The method for establishing and processing of fluid units in a conduit the length of which corresponds to the length of sing steps are ¥-e-fc-g-a-e-fcnftfe-L--τηονβτηβττίτ- elative Lo~*gach~Dtrher and at least one opening spaced along the length thereof comprising the steps of moving a selected plurality of said portions in a manner effective to establish a plurality of spaced releasable rollers hydga¾a4 -e- scale internally of said conduit such that formation of said fluid into a stream is avoided throughout said processing path and the conduit is formed into a plural series of rollers hydraulically isolated chambers defined by said se«ie and having the conduit as a common envelope; moving the seats- relative to the conduit to cause the chambers to move along the length of said path thereby causing said chambers to be successively presented to said opening; and selectively adding, processing or removing fluid through said opening as each chamber is presented thereto according to a program of operations for the fluid unit in such chamber and independent of operations performed on the fluid unit in any other such chamber . 16 17.-IS. The method of Claim wherein said step of moving said portions comprises the step of continuously compressing said portions to form and continuously maintain the rollers spacing and hydraulic effectiveness of said seals ■ 16 18. r9. The method of Claim if including the steps of: forming a permanent non-releasable seal internally of said conduit at a selected location and arranged so that the fluid in each chamber arriving at such location is divided into a plurality of portions some of which are free to flow past said location and others of which are blocked at such location; and moving each chamber and the fluid unit contained therein past said location thereby enabling said blocked portions to be removed at such locations . 16 19. -2-Θ-. The method of Claim including the step of connecting said opening to constant volume pump and exchanging known volumes of fluid through said opening with any chamber communicating therewith. 16 20.-21. The method of Claim 4? including the step of deforming selected said chambers externally of said conduit rollers while said aea-le- are moving and maintaining the resulting deformation for sufficient time to effect internal mixing in the contents of said selected chambers. 16 21. -22. The method of Claim i wherein said conduit further includes a permeable membrane mounted internally of and sealed to said conduit in a manner directed to establishing a subsidiary permeable conduit having closed ends and in said moving step to establish said seals, moving both said membrane and said conduit such that said seals and chambers are continuously formed in both said conduit and said subsidiary conduit and including the step of admitting a recipient fluid in the chambers so formed in said conduit and a donor fluid in the chambers so formed in said subsidiary conduit and during the rollers step in which said a- a-lra- are moving effecting dialysis between said recipient and donor fluids. 22. -2 . Apparatus for processing of fluid in units substantially as described hereinbefore with reference to any of the Figures in the Drawings. COHEN <2 ZEDEK & SPISBACH P. O. Box 1169, Te!-Aviv Attorneys for Applicant