US3600953A - Method and apparatus for the introduction of auxiliary separating fluid in fluid sample analyses means - Google Patents

Method and apparatus for the introduction of auxiliary separating fluid in fluid sample analyses means Download PDF

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US3600953A
US3600953A US854337A US3600953DA US3600953A US 3600953 A US3600953 A US 3600953A US 854337 A US854337 A US 854337A US 3600953D A US3600953D A US 3600953DA US 3600953 A US3600953 A US 3600953A
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fluid
separating
separating fluid
analysis means
another
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Jack Isreeli
Aaron Kassel
Richard H Heimann
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Technicon Corp
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Technicon Corp
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/08—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis

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  • e an comprise me o m r uce series 0 spaced bubbles of said separating fluid to a stream of successive- [52] [1.8.61 73/423 A, sive fl id sampk portions fl i in a fl id Samp
  • Such prior art analysis means additionally include means formed by said pump means to add a separating fluid such as air to a fluid sample portion stream to segmentize the same and promote essential fluid sample analysis means cleansing and fluid sample color producing reagent mixing, as well as debubbler means which are effective to remove all of said separating fluid from said fluid sample portion stream prior to the flow thereof through said flow cell.
  • a separating fluid such as air
  • debubbler means which are effective to remove all of said separating fluid from said fluid sample portion stream prior to the flow thereof through said flow cell.
  • an object of this invention to provide new and improved method and apparatus for the introduction of an auxiliary separating fluid into the fluid sample streams of automatic colorimetric fluid sample analysis means, and the flow of a portion, at least, of said auxiliary separating fluid through the flow cell of such analysis means to effect satisfactory, intersample cleansing of said flow cell.
  • Another object of this invention is the provision of method and apparatus as above which are operative to introduce said auxiliary separating fluid into discrete flow paths of such analysis means in substantially perfect phase relationship.
  • Another object of this invention is the provision of apparatus as above which requires the use of only readily available components of proven dependability in the fabrication thereof and insures long periods of satisfactory, maintenancefree operation thereof.
  • a further object of this invention is the provision of method and apparatus as above which are particularly adaptable for use in conjunction with advanced versions of automatic analysis means as shown and described in US. Pat. Nos. 3, l 34,263 and 3,241,432.
  • the new and improved method and apparatus for the introduction of auxiliary separating fluid are useful in conjunction with fluid sample analysis means which provide for the concomitant flow of a series of fluid-segmented fluid sample portions through one analysis means conduit, and a fluid-segmented liquid in the nature of a recipient stream through another analysis means conduit.
  • the method and apparatus of the invention provide for the introduction of an auxiliary separation fluid bubble at the beginning and end of each of said fluid sample portions, the detection of each of said bubbles, and the subsequent introduction of a substantially correspondingly sized and located auxiliary separating fluid bubble in said recipient stream.
  • debubbler means which are effective to remove all of said segmenting fluid and parts, only, of said auxiliary separating fluids, leaving the remainders of the latter to flow through the fluid sample analysis means flow cells for the requisite intersample cleansing thereof.
  • the method and apparatus provide for the substantially concomitant introduction of said auxiliary separating fluids at corresponding locations in said fluid sample analysis means conduits.
  • FIGS. IA and IB show a generally schematic flow diagram of fluid sample analysis means incorporating a first form of the new and improved auxiliary separating fluid introduction means of the invention.
  • FIG. 2 is a generally schematic flow diagram of the same fluid sample analysis means incorporating a second form of the new and improved auxiliary separating fluid introduction means of the invention.
  • fluid analysis means incorporating a first form of the new and improved auxiliary separating fluid introduction apparatus constructed and operative in accordance with the teachings of this invention may, for example, take the general form of those shown and described in US. Pat. No. 3,134,263 issued May 26, I964 to E. B. M. DeJong, and US. Pat. 3,24l,432 issued Mar. 22, I966 to Leonard T. Skeggs et al., respectively, and, as depicted in FIGS. IA and 18 may be understood to be somewhat simplified in that only those portions thereof which are considered necessary to the full disclosure of this invention are specifically shown and described.
  • the fluid sample analysis means comprise a sample supply device I2 which, as disclosed in said US. Pat. No. 3,134,263, includes a turntable 14 upon which are disposed a plurality of fluid sample containers l6, and adjacent to which is disposed a wash liquid receptacle 18.
  • Sample offtake means are indicated at 20 and comprise a sample offiake tube 22 which is movable from the depicted position thereof wherein the tube inlet end is immersed in a sample container 16, to another position thereof wherein the said inlet end is immersed in the wash liquid receptacle 18.
  • the turntable I4 is intermittently rotatable, under the control of nonillustrated sample supply device drive means, to successively present each of the fluid sample containers 16 to the sample offtake means 20, while the latter are operable, under the control of said sample supply device drive means, to alternately position the inlet end of the ofltake tube 22 in a thusly presented fluid sample container 16 and the wash liquid receptacle 18.
  • Peristaltic pump means are indicated generally at 24 and, as disclosed in said U.S. Pat. No. 3,241,432, may be understood to comprise a series of nonillustrated pump rollers which are operable as indicated by pump drive means 25 to compress or occlude compressible pump tubes 26, 28, 29, 30, 31 and 32 longitudinally thereof in the direction from left to right as seen in H6. 1 to pump fluids therethrough in the said direction.
  • sample supply means 12 and the peristaltic pump means 24 will be efiective to supply a series of different sample portions, as indicated at 5,, S, and S from successive ones of the sample containers 16 to a connected conduit 34', and that the said sample portions will be spaced, as shown, at both the upstream and downstream ends thereof by a segment of air, indicated as A, which is aspirated through offtake tube 20 as the latter is moved through the ambient air from a sample container 16 to the wash liquid receptacle 18, a segment of wash liquid, indicated as W, which is aspirated through offiake tube 22 when the inlet end thereof is immersed in the said wash liquid receptacle, and another segment of air A which is aspirated through said offtake tube as the latter is again moved through the ambient air from the said wash liquid receptacle to the next presented sample container 16.
  • A segment of air
  • W wash liquid
  • a conduit 36 connects the outlet end of compressible pump tube 26 to the inlet port of a remotely controllable, two-way valve 38, while a branch conduit 40 connects one outlet port of the said valve to conduit 34.
  • the other outlet port of the two-way valve 38 communicates as indicated with the atmosphere.
  • a conduit 42 is connected to the outlet end of compressible pump tube 30, while the inlet end of said compressible pump tube is immersed, as indicated, in a container 124 of a suitable fluid, whereby may be understood that operation of the peristaltic pump means 24 results in supply of a stream of said fluid, indicated as R, to conduit 42.
  • a conduit 44 connects the outlet end of compressible pump tube 32 to the inlet port of a remotely controllable, two-way valve 46, while a branch conduit 48 connects one outlet port of valve 46 to conduit 42.
  • the other outlet port of valve 46 communicates as indicated, with the atmosphere.
  • Valve 38 is arranged so that, in one position the same is effective to connect conduits 36 and 40 and, in the other position, to disconnect these conduits and vent conduit 36, to atmosphere. ln like manner, valve 46 is arranged so that, in one position conduits 44 and 48 are connected while, in the other position these conduits will be disconnected and conduit 44, is vented to atmosphere.
  • a branch conduit connects the outlet end of compressible pump tube 29 to the conduit 34 upstream of the connection of conduit therewith.
  • a branch conduit 37 connects the outlet end of compressible pump tube 31 to the conduit 42 upstream of the connection of conduit 48 therewith.
  • conduits 34 and 42 operation of the peristaltic pump means will be eflective to continually supply pressurized air to each of conduits 34 and 42. More specifically, and with regard to conduit 34, it may be understood that this pressurized air will be effective to segmentize the respective fluid sample portions and wash liquid segments flowing therethrough by the formation of segmenting air bubbles AS and AW, as indicated. In like manner and with regard to conduit 37, it may be understood that this pressurized air will be effective to segmentize the fluid stream R flowing therethrough by the formation of segmenting air bubbles AR, as indicated.
  • a dialyzer which may, for example, take the form of that shown and described in said U.S. Pat. No. 3,241,432, is indicated at 50 and may be understood to comprise a donor stream side 52 and a recipient stream side 54.
  • the conduit 34 is connected, as shown, to the inlet of the donor stream side 52 and the conduit 42 is connected as shown to the inlet of the recipient stream side 54 of the dialyzer 50.
  • Debubbler means which may, for example, take the form of those shown and described in said U.S. Pat. No. 3,24l,432,
  • conduit 58 extends as shown to connect the outlet of the donor stream side 52 to the inlet of the said debubbler means.
  • Debubbler means of like construction are indicated at 60, and a conduit 62 extends as shown to connect the outlet of the recipient stream side 54 to the inlet of the debubbler means 60.
  • Colorimeters which may, for example, take the form of those shown and described in said U.S. Pat. No. 3,24l,432 are indicated in dashed lines at 64 and 66, respectively, and include flow cells 68 and 70 having respective sight passages 72 and 74 formed therein.
  • a conduit 76 connects the outlet of debubbler means 56 to the inlet of flow cell 68, while a conduit 78 connects the outlet of debubbler means 60 to the inlet offlow cell 70.
  • colorimeter 64 Further included in colorimeter 64 are a light source 80 and photoelectric detector means 82 disposed as shown adjacent opposite extremities of the flow cell sight passage 72 to enable the colorimetric analysis of fluids flowing therethrough in a manner known to be well understood by those skilled in the art.
  • colorimeter 66 includes a light source 84 and photoelectric detector means 86 disposed and operative, as described above, with regard to sight passage 74 of flow cell 70.
  • Stepping switch means 88, and strip chart recorder means 90 are connected as shown to the respective photoelectric detector means outputs by leads 92 and 94, respectively to provide for the sequential recording on recorder chart 98 of the results of the colorimetric analyses performed by colorimeters 64 and 66, again in a manner known to be well understood by those skilled in this art.
  • Auxiliary separating fluid detecting means are indicated generally at 100 and, as depicted, take the form of an infrared energy source 102 and infrared filter means 104 disposed as shown to one side of conduit 34-h being understood that conduit 34 is constructed from a material with good infrared energy transmission characteristics in the nature of clear glass-and infrared detector means 106 disposed as shown to the opposite side of said conduit in substantial alignment with infrared energy source 102.
  • a differential amplifier is indicated at 108 and is connected as shown to the output side of the detector means 106 by lead 110, while a lead 112 connects the output side of said dif ferential amplifier to delay timer means 114.
  • Valve operating means which may, for example, take the form of a valve operating solenoid, to operate valve means 46, are indicated at 116 and are connected as shown to the output side ofthe delay timer means 114 by lead 118.
  • the auxiliary separating fluid detecting means 100 are operative upon detection of an auxiliary separating fluid or air bubble ASD to start delay timer means 114 which, after the expiration of a predetermined time period, operates valve 46, through valve operating solenoid 116, to connect conduits 44 and 48, so as to supply an auxiliary separating fluid into the recipient stream along conduit 42 for a time period sufiicient to form an air bubble ASR therein of substantially the same extent as the detected air bubble ASD.
  • differential amplifier means 108 are operative to provide an output on lead 112 effective to activate or start delay timer means 114 only when the output on lead from detector means 106 exceeds a predetermined threshold, and said detecting means are in turn arranged to provide such threshold exceeding output only upon the sensing thereby of an auxiliary separating fluid or air bubble of the extent of the auxiliary air bubble ASD.
  • valve operating means 120 which may, for example, take the form of a valve operating solenoid, and that the latter are connected as indicated by lead 122 to the pump drive means 25, to provide for the operation of the said valve means in substantial synchronization with the operation of the said pump drive means. More specifically, it may be understood that pump drive means 25 and valve operating means 120 are arranged and the latter programmed to operate valve 38, so as to connect conduits 36 and 40 for a predetermined time period and supply an auxiliary separating fluid or air bubble ASD, of predetermined extent as determined by said time period, to the donor stream flowing along conduit 34 as each of the downstream and upstream ends of the fluid sample portions 5,, 8,, 8,, etc. reach the juncture of conduit 40 and conduit 34.
  • auxiliary separating fluid introduction system of the invention depicted in FIG. 2, it may be seen that the same is substantially similar to that of FIGS. 1A and 1B and like reference numerals are utilized to identify like system components.
  • the auxiliary separating fluid or air bubble detection means 100 are eliminated and that the valve 46 is operated, as indicated by lead 124, from the same pump drive means source 25 as is the valve 38, and in synchronism therewith.
  • conduit 48 and conduit 42 is moved into substantial alignment with the juncture of conduit 40 and conduit 34 whereby the auxiliary separating fluid or air bubbles ASD and ASR will be introduced to said donor and recipient stream conduits 42 and 34 at substantially corresponding locations in the respective donor and recipient streams flowing therethrough.
  • FIGS. 1A and 1B OPERATION in operation of the invention form of FIGS. 1A and 1B for use, for example, in the automatic sequential analysis of blood serum samples in advanced versions of the fluid sample analysis means as disclosed in said US. Pat. No. 3,134,263 and 3,24I,432, wherein extremely small blood serum sample portions in the order of 0.1 or 1.2 ml. are supplied to the analysis means at extremely high sampling rates in the order of 300 per hour.
  • each of fluid sample containers 16 would be filled with a different blood serum sample
  • flask 124 would be filled with a liquid in the nature of water of clinical purity for the aspiration thereof through compressible pump tube 30 to form a recipient stream
  • the respective inlet ends of compressible pump tubes 26, 29, 31 and 32 would be left open to atmosphere-although suitable, nonillustrated air filter means could, of course, be operatively disposed therein-to provide for the aspiration of air therethrough upon operation of the peristaltic pump means 24.
  • auxiliary air bubbles ASR and ASD- which are, of course, of greater volume than the respective segmenting air bubbles AW
  • AS and ARthe respective internal diameters of the compressible pump tubes 26 and 32 may be made larger than the respective internal diameters of the compressible pump tubes 28, 29, 30 and 31, so as to increase the fluid-flow rate through the former upon operation of the peristaltic pump means 24 and insure the provision of sufficient pressurized air to valve means 38 and 46 for the formation, on demand, of the said auxiliary air bubbles in the respective donor stream conduit 34 and recipient stream conduit 42.
  • pump drive means 25, or suitable timer means which may be operatively associated therewith would be programmed to operate valve means 38 to connect conduits 36 and 40 for a time period predetermined to provide an auxiliary air bubble ASD of predetermined extent to the donor stream every time a leading or trailing edge of a fluid sample portion S arrives at the juncture of conduits 40 and 34, while delay timer means 1l4 would be programmed to provide, through operation of valve means 46, an auxiliary air bubble ASR of substantially the same predetermined extent in response to each starting or activation thereof.
  • the width of the transmission path of infrared energy between energy source 102 and detector means 106 will be established so that only an auxiliary air bubble ASD or, more significantly, not an intrawash liquid segment air bubble AW or an intrasample air bubble AS, will be effective to enable an output from detector I06 on lead exceeding the threshold level of differential amplifier 108.
  • the pump drive means 25 will be operative to operate valve means 38 to connect conduits 36 and 40 for a predetermined period of time to introduce an auxiliary air bubble to the recipient stream for combination with the air bubble A to form the auxiliary air bubble as indicated at ASD,.
  • valve means 38 will be operated to disconnect conduits 36 and 40 and vent conduit 36 to atmosphere, so as to discontinue the supply of air to conduit 34 while enabling the necessary venting to atmosphere of the compressed air being constantly supplied thereto by operation of pump means 24 and attendant compression of pump tube
  • Each auxiliary air bubble, thus formed, will be flowed by the flow of the donor stream to the position thereof indicated at ASD, in FIG. 1A whereby the same will occupy that portion of the donor stream conduit 34 which lies in the transmission path of the infrared energy source 102 to detector means 106.
  • the level of infrared energy transmitted between said source and detector will be sharply increased-the infrared energy transmission characteristics of air being, of course, much greater than those of either the blood serum samples or wash liquid-whereby the output from detector means 106 on lead 110 will exceed the predetermined threshold level of differential amplifier 108 to result in the starting or activation of the delay timer means l 14 thereby.
  • delay timer means 114 will be effective to operate valve means 46 to connect conduits 44 and 48 for a period of time sufficient to introduce an auxiliary air bubble ASR into the recipient stream flowing in conduit 44, and it is made particularly clear that the said auxiliary air bubble ASR will be of substantially the same extent as the relevant auxiliary air bubble ASD, and will be disposed in the recipient stream at substantially the same location as the auxiliary air bubble ASD is disposed in the donor stream. This is to say, the said auxiliary air bubbles will be in substantially perfect phase relationship.
  • valve means 38 will be effective to introduce an auxiliary air bubble ASD at the respective downstream and upstream sides of each of the blood serum sample portions 5,, S 8;, etc. as the same are pumped past the juncture of conduits 40 and 34.
  • auxiliary air bubbles ASD As each of the said auxiliary air bubbles ASD passes in donor stream conduit 34 through the transmission path of detector means 100, the same will be operable, through delay timer means 114, and after the expiration of a time period predetermined to enable the said auxiliary air bubble ASD to reach the location indicated at ASD -,to control valve 46 to introduce a correspondingly sized and located auxiliary air bubble ASR to the recipient stream in conduit 42.
  • the donor stream will flow through conduit 58 to and through the debubbler means 56, while the recipient stream will flow through conduit 62 to and through the debubbler means 60.
  • the said donor stream will be constituted by the respective blood serum sample portions 5,, 8,, 8,, etc. as segmented by the intrasample air bubbles AS and as separated by the auxiliary air bubbles ASD, the wash liquid segments W, as segmented by the intraportion air bubbles AW.
  • the recipient stream Upon entry into debubbler means 62, the recipient stream will be constituted by the portions of the recipient stream liquid as separated, one from the other, by the auxiliary air bubbles ASR and as segmented by the intraportion air bubbles AR.
  • the gas removal capacity of the latter is predetermined to be sufficient to remove to atmosphere all of the intrasample air bubbles AS and all of the wash liquid segment air bubbles AW therefrom while removing a portion, only, of the auxiliary air bubbles ASD therefrom, whereby the donor stream which flows from the debubbler means 56 through conduit 76 to and through the flow cell 68 of colorimeter 64 will be constituted, as shown, by the continuous blood serum sample portions separated, each from the other, by the remaining portions of the auxiliary air bubbles ASD as separated by the recombined wash liquid segment W.
  • the total volume of the sight passage 72 of flow cell 68 is made less than the total volume of each of the continuous sample portions 8,, 8,, 8,, etc. whereby may be understood that a predetennined period of colorimetric analysis time will be provided during which the entire sight passage is filled, as depicted, with the said sample portion. It is, of course, during this period of time that the output of photoelectric detector means 82 will be fed, through stepping switching means 88, and along lead 96 to operate strip chart recorder means 90 to provide a permanent record of such colorimetric analysis on the recorder strip chart 98.
  • an auxiliary air bubble ASD will be flowed through the flow cell 68 immediately prior to and immediately after the flow of each of said sample portions therethrough, and that the cleansing effect of this auxiliary air bubble flow, as enhanced by the flow of the wash liquid segment W through the said flow cell, will be effective to cleanse the flow cell 68 to the extent that contamination of successive sample portions will be substantially prevented to ensure the accuracy of the colorimetric analyses of all of said sample portions.
  • the gas removal capacity of the latter is predetermined to be sufficient to remove to atmosphere all of the air bubbles AR while removing a portion, only, of the auxiliary air bubbles ASR therefrom.
  • the recipient stream which flows from the debubbler means 60 through conduit 78 to and through the flow cell 70 of colorimeter 66 will be constituted, as shown, by the continuous recipient stream portions RD containing the dialyzed constituent of interest and separated, each from the other, by the remaining portions of the auxiliary air bubbles ASR, as separated by the substantially pure segments of the recipient stream R which passed through the dialyzer means 50 concomitantly with the wash liquid segments W and the air bubbles AW.
  • the total volume of sight passage 74 of flow cell 70 is made less than the total volume of each of the continuous recipient stream portions RD, whereby the depicted flow cell condition will, of necessity, occur to enable meaningful colorimetric analyses of the RD portions.
  • an auxiliary air bubble ASR will be flowed through the flow cell 70 immediately prior to and after the flow of each of said continuous recipient stream portions RD therethrough, and that the cleansing effect of this auxiliary air bubble flow, as enhanced by the flow of the substantially pure recipient stream portion R through the said flow cell, will be effective to cleanse the flow cell 70 to the extent that contamination of successive recipient stream portions RD will be substantially prevented to ensure the accuracy of the colorimetric analyses of all of said recipient stream portions RD.
  • auxiliary air bubbles Of additional significance and advantage with regard to the passage of auxiliary air bubbles through the analysis means flow cells 68 and 70 is the fact that the same will provide for the clear delineation on the recorder strip chart 98 of the successively recorded results of the colorimetric analyses of the respective sample and recipient stream portions. Since an auxiliary air bubble both immediately precedes and follows the flow of each of said stream portions and since the light transmission characteristics of air are substantially difierent than those of the liquids ofinterest, passage of the auxiliary air bubble through the flow cells 68 and 70 will result in the provision on the recorder strip chart 98 of clearly discernible indicia to mark the beginning and end of the passage of each of said stream portions through said flow cells.
  • the form of FIG. 2 offers the advantage of system simplicity in that detecting means 100, along with delay timer means 114, are eliminated therein.
  • a problem which may, however, arise in the operation of the apparatus form of FIG. 2 resides in the fact that, although the respective auxiliary air bubbles ASD and ASR are simultaneously introduced at substantially corresponding locations in the respective donor and recipient stream conduits 34 and 42, the nature and/or extent of the conduits between these corresponding locations of auxiliary air bubble introduction and the respective entries thereof into the dialyzer means 50 may result in the degradation of the essential phase relationship between the auxiliary air bubbles, with the probably intolerable result that the essential phase relationship for the passage of the respective donor and recipient stream portions through the said dialyzer means will be likewise degraded.
  • the system of the invention has been disclosed for use in analysis systems wherein both the donor and recipient streams are colorimetrically analyzed, it may be understood that the invention system could equally well be utilized in analysis systems wherein the donor stream is flowed to waste upon exit from the dialyzer. Notwithstanding, the introduction of the auxiliary air bubbles ASD would provide the advantageous cleansing and discrete sample portion delineation functions during the flow thereof through the donor conduit and dialyzer means.
  • conduit 40 and possibly valve means 38 for use in fluid sample analysis means as discussed hereinabove wherein the aspirated fluid sample is divided into a plurality of fluid sample portions for flow in individual conduits immediately downstream of the peristaltic pump means 24.
  • valve-controlled conduit 40 being connected to recipient stream conduit 42 at a corresponding location therein and operative, under the control of the pump drive means 25, to periodically introduce an auxiliary air bubble ASR therein to delineate the segmented recipient stream into the stream portions R.
  • the detecting means 100 rearranged to detect the flow of said auxiliary air bubbles ASR at a corresponding location in the said recipient stream conduit, while the valve-controlled conduit 48 is connected to donor stream conduit 34 at a corresponding location and is operative appropriately introduce the auxiliary air bubbles ASD thereto at the leading and trailing edge of the respective segmented sample portions 8,, S, S etc., in response to the detection of the appropriately phased auxiliary air bubbles ASR in the recipient stream conduit by the detecting means 100.
  • Apparatus for the introduction of separating fluid to fluid sample analysis means comprising: means for directing a first liquid stream of successive samples along a fluid analysis flow path and a second liquid stream along a fluid analysis flow path, means for intermittently introducing a separating fluid portion into said fluid sample analysis means flow path and between successive ones of said samples in said first liquid stream, means for intermittently introducing another separating fluid portion into said another fluid sample analysis means flow path and into said second liquid stream, said separating fluid portion and said another separating fluid portion being immiscible with respect to said first and second liquid streams, respectively, said introducing means being operative to introduce said separating fluid portion and said another separating fluid portion into said first and second liquid streams, respectively, in particular phase relationship, such that said separating fluid portion and said another separating fluid portion flow through respective one of said fluid sample analysis means flow paths in said particular phase relationship.
  • said separating fluid portion and said another separating fluid portion are respectively introduced into said fluid sample analysis means flow paths at different locations therein, said means to introduce another separating fluid portion being operatively associated with said another fluid sample analysis means flow path at location therein corresponding to a location in said fluid sample analysis means flow path which is downstream of the location at which said separating fluid portion is introduced thereto, and said means to introduce said another separating fluid portion being operable only when said separating fluid portion has reached said downstream location in said fluid analysis means flow path, whereby said separating fluid portion and said another separating fluid portion will be in substantial phase relationship.
  • said fluid analysis means includes a flow cell having a sight passageway, and a part, at least, of at least one of said separating fluid portions is effective to flow through the sight passage of said fluid analysis means flow cell.
  • said means to introduce said another separating fluid portion comprise means to detect the flow of said separating fluid portion in said fluid sample analysis means flow path, and means responsive to said detecting means to operate said means to introduce said another separating fluid portion.
  • said detecting means are operative to detect said separating fluid portion at a loca tion in said fluid sample analysis means flow path intermediate said portion introduction location and said downstream location, and said operating means comprise delay means which are operable to delay operation of said means to introduce said another separating fluid portion until said fluid separating portion has been flowed from said intermediate location to said downstream location.
  • said separating fluid portion and said another separating fluid portion are substantially concomitantly introduced into said fluid sample analysis means flow paths at substantially corresponding locations therein, whereby said separating fluid portion and said another separating fluid portion will be in substantial phase relationship.
  • said fluid analysis means includes a flow cell having a sight passageway, and a part, at least, of at least one of said separating fluid portions is effective to flow through the sight passage of said fluid analysis means flow cell.
  • said fluid analysis means includes a flow cell having a sight passageway, and a part, at least, of at least one of said separating fluid portions is effective to flow through the sight passage of said fluid analysis means flow cell.
  • said fluid analysis means includes a flow cell having a sight passageway, and a part, at least, of at least one of said separating fluid portions is effective to flow through the sight passage of said fluid analysis means flow cell.
  • said fluid sample analysis means comprise pump means and dialyzer means
  • said fluid sample analysis means flow path comprises a conduit connecting said pump means and the donor side of said dialyzer means
  • said another fluid sample analysis means flow path comprises another conduit connecting said pump means and the recipient side of said dialyzer means
  • said means to introduce said separating fluid portion comprise valve controlled conduit means connecting said pump means and one of said conduits at a location intermediate said pump means and said dialyzer means
  • said means to introduce said another separating fluid portion comprise other valve controlled conduit means connecting said pump means and the other of said conduits at a corresponding location intermediate said pump means and said dialyzer means.
  • said fluid sample analysis means comprise pump means and dialyzer means
  • said fluid sample analysis means flow path comprises a conduit connecting said pump means and the donor side of said dialyzer means
  • said another fluid sample analysis means flow path comprises another conduit connecting said pump means and the recipient side of said dialyzer means
  • said means to introduce said separating fluid portion comprise valve controlled conduit means connecting said pump means and one of said conduits at a location intermediate said pump means and said dialyzer means
  • said means to introduce said another separating fluid portion comprise other valve controlled conduit means connecting said pump means and the other of said conduits at a location intermediate said pump means and said dialyzer means but closer to said dialyzer means than the connection location of said valve controlled conduit means.
  • said fluid sample analysis means are operative to flow a stream of successive portions of different fluid samples through said fluid analysis means flow path, and said means to introduce said separating fluid portion into said flow path are operative to introduce the same thereinto substantially at the beginning and end of each of said different fluid sample portions during the flow of the latter therethrough.
  • said fluid sample analysis means are operative to flow a stream of successive portions of different fluid samples through said fluid analysis means flow path, and said means to introduce said separating fluid portion into said flow path are operative to introduce the same thereinto substantially at the beginning and end of each of said different fluid sample portions during the flow of the latter therethrouph.
  • a method or introducing a separating fluid to fluid sample analysis means the steps of, intermittently introducing a separating fluid portion into a fluid sample analysis means flow path directing a first liquid stream of successive samples, so as to be disposed between successive ones of said samples, intermittently introducing another fluid sample analysis means flow path directing a second liquid stream and in particular phase relationship with said separating fluid portion introduced between successive samples in said first liquid stream, said separating fluid portion and said another separating fluid portion being immiscible with respect to said first and second liquid streams, respectively.

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US854337A 1969-07-25 1969-07-25 Method and apparatus for the introduction of auxiliary separating fluid in fluid sample analyses means Expired - Lifetime US3600953A (en)

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AU (1) AU1737770A (enrdf_load_stackoverflow)
BE (1) BE753912A (enrdf_load_stackoverflow)
CH (1) CH514137A (enrdf_load_stackoverflow)
DE (1) DE2036262A1 (enrdf_load_stackoverflow)
FR (1) FR2055585A5 (enrdf_load_stackoverflow)
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* Cited by examiner, † Cited by third party
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US4022575A (en) * 1974-09-16 1977-05-10 Block Engineering, Inc. Automatic chemical analyzer
DE2740570A1 (de) * 1976-09-15 1978-03-16 Bifok Ab Automatische analyse von alkalimetallen, halogeniden und dergleichen durch verwendung von ionenselektiven elektroden
US4212845A (en) * 1977-07-06 1980-07-15 The Rank Organisation Limited Analytical apparatus
FR2451579A1 (fr) * 1979-03-16 1980-10-10 Technicon Instr Procede et appareil pour la determination par l'exterieur des caracteristiques d'un fluide segmente
US4253846A (en) * 1979-11-21 1981-03-03 Technicon Instruments Corporation Method and apparatus for automated analysis of fluid samples
US4300906A (en) * 1980-10-06 1981-11-17 Technicon Instruments Corp. Method for the operation of automated analysis apparatus
FR2484652A1 (fr) * 1980-06-12 1981-12-18 Kyoto Daiichi Kagaku Kk Procede et appareil de determination quantitative du degre d'agglutination de particules
WO1983003009A1 (en) * 1982-02-22 1983-09-01 Beckman Instruments Inc Method and apparatus for detecting insufficient liquid sample quantity
US4526754A (en) * 1982-07-30 1985-07-02 Technicon Instruments Corporation Sample transport system
US4798803A (en) * 1985-07-10 1989-01-17 The Dow Chemical Company Method for titration flow injection analysis
WO1989000698A1 (en) * 1985-11-08 1989-01-26 Wessex Instrumentation Ltd. Continuous flow analysis
US5094961A (en) * 1990-12-13 1992-03-10 Coulter Corporation Aspiration method for hematology analyzing apparatus
US5268147A (en) * 1992-02-26 1993-12-07 Miles, Inc. Reversible direction capsule chemistry sample liquid analysis system and method
US5380665A (en) * 1989-03-27 1995-01-10 International Technidyne Corporation Fluid sample collection and delivery system and methods particularly adapted for body fluid sampling
US5517870A (en) * 1992-12-25 1996-05-21 Hitachi, Ltd. Intra-liquid particle classification apparatus using light scattering
US5542444A (en) * 1994-11-07 1996-08-06 Abbott Laboratories Valve and method of using
US5559339A (en) * 1994-10-31 1996-09-24 Abbott Laboratories Method and apparatus for verifying dispense of a fluid from a dispense nozzle
US5743295A (en) * 1995-07-20 1998-04-28 Abbott Laboratories Valve construction and method of use
US5775371A (en) * 1995-03-08 1998-07-07 Abbott Laboratories Valve control
US5834314A (en) * 1994-11-07 1998-11-10 Abbott Laboratories Method and apparatus for metering a fluid
US5967163A (en) * 1996-01-30 1999-10-19 Abbott Laboratories Actuator and method
US6485980B1 (en) * 1998-07-06 2002-11-26 Bayer Corporation Method and apparatus for controlling a stream of liquid test packages in a capsule chemistry analysis system
US6488894B1 (en) * 1997-11-19 2002-12-03 Biognosis Gmbh Device for sequential discharge of flowable reagents
JP2004317420A (ja) * 2003-04-18 2004-11-11 Hitachi Software Eng Co Ltd キャピラリー利用測定装置
US6902938B1 (en) * 2000-10-10 2005-06-07 Jeol Usa, Inc. Chemical analysis method for multiplexed samples
WO2005084547A1 (en) * 2004-03-05 2005-09-15 Datainnovation I Lund Ab System and method for automatic taking of fluid samples
US20060195046A1 (en) * 2005-02-14 2006-08-31 Sterling Bernhard B Analyte detection system with reduced sample volume
US9863837B2 (en) 2013-12-18 2018-01-09 OptiScan Biomedical Coporation Systems and methods for detecting leaks
US11426726B2 (en) 2018-04-02 2022-08-30 Dropworks, Inc. Systems and methods for serial flow emulsion processes

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Cited By (48)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4022575A (en) * 1974-09-16 1977-05-10 Block Engineering, Inc. Automatic chemical analyzer
US4004451A (en) * 1974-12-24 1977-01-25 Technicon Instruments Corporation Automated timing of fluid delivery in sample analysis
DE2740570A1 (de) * 1976-09-15 1978-03-16 Bifok Ab Automatische analyse von alkalimetallen, halogeniden und dergleichen durch verwendung von ionenselektiven elektroden
US4227973A (en) * 1976-09-15 1980-10-14 Bifok Ab Automatic analysis of alkali metals halides etc. by means of the use of ion-selective electrodes
US4212845A (en) * 1977-07-06 1980-07-15 The Rank Organisation Limited Analytical apparatus
FR2451579A1 (fr) * 1979-03-16 1980-10-10 Technicon Instr Procede et appareil pour la determination par l'exterieur des caracteristiques d'un fluide segmente
US4253846A (en) * 1979-11-21 1981-03-03 Technicon Instruments Corporation Method and apparatus for automated analysis of fluid samples
FR2484652A1 (fr) * 1980-06-12 1981-12-18 Kyoto Daiichi Kagaku Kk Procede et appareil de determination quantitative du degre d'agglutination de particules
US4398894A (en) * 1980-06-12 1983-08-16 Kabushiki Kaisha Kyoto Daiichi Kagaku Method for quantitatively determining the degree of agglutination of particles
US4300906A (en) * 1980-10-06 1981-11-17 Technicon Instruments Corp. Method for the operation of automated analysis apparatus
WO1983003009A1 (en) * 1982-02-22 1983-09-01 Beckman Instruments Inc Method and apparatus for detecting insufficient liquid sample quantity
US4419903A (en) * 1982-02-22 1983-12-13 Beckman Instruments, Inc. Method and apparatus for detecting insufficient liquid levels
US4526754A (en) * 1982-07-30 1985-07-02 Technicon Instruments Corporation Sample transport system
US4798803A (en) * 1985-07-10 1989-01-17 The Dow Chemical Company Method for titration flow injection analysis
WO1989000698A1 (en) * 1985-11-08 1989-01-26 Wessex Instrumentation Ltd. Continuous flow analysis
US5380665A (en) * 1989-03-27 1995-01-10 International Technidyne Corporation Fluid sample collection and delivery system and methods particularly adapted for body fluid sampling
US5094961A (en) * 1990-12-13 1992-03-10 Coulter Corporation Aspiration method for hematology analyzing apparatus
US5268147A (en) * 1992-02-26 1993-12-07 Miles, Inc. Reversible direction capsule chemistry sample liquid analysis system and method
US5517870A (en) * 1992-12-25 1996-05-21 Hitachi, Ltd. Intra-liquid particle classification apparatus using light scattering
US5559339A (en) * 1994-10-31 1996-09-24 Abbott Laboratories Method and apparatus for verifying dispense of a fluid from a dispense nozzle
US5542444A (en) * 1994-11-07 1996-08-06 Abbott Laboratories Valve and method of using
US5834314A (en) * 1994-11-07 1998-11-10 Abbott Laboratories Method and apparatus for metering a fluid
US5794641A (en) * 1995-03-08 1998-08-18 Abbott Laboratories Valve control
US5791375A (en) * 1995-03-08 1998-08-11 Abbott Laboratories Valve control
US5775371A (en) * 1995-03-08 1998-07-07 Abbott Laboratories Valve control
US5743295A (en) * 1995-07-20 1998-04-28 Abbott Laboratories Valve construction and method of use
US5967163A (en) * 1996-01-30 1999-10-19 Abbott Laboratories Actuator and method
US6488894B1 (en) * 1997-11-19 2002-12-03 Biognosis Gmbh Device for sequential discharge of flowable reagents
US20030039588A1 (en) * 1997-11-19 2003-02-27 Peter Miethe Device for sequential discharge of flowable reagents
US6485980B1 (en) * 1998-07-06 2002-11-26 Bayer Corporation Method and apparatus for controlling a stream of liquid test packages in a capsule chemistry analysis system
US6872571B1 (en) * 1998-07-06 2005-03-29 Bayer Corporation Method and apparatus for controlling a stream of liquid test packages in a capsule chemistry analysis system
US6902938B1 (en) * 2000-10-10 2005-06-07 Jeol Usa, Inc. Chemical analysis method for multiplexed samples
JP2004317420A (ja) * 2003-04-18 2004-11-11 Hitachi Software Eng Co Ltd キャピラリー利用測定装置
WO2005084547A1 (en) * 2004-03-05 2005-09-15 Datainnovation I Lund Ab System and method for automatic taking of fluid samples
US20070191735A1 (en) * 2004-03-05 2007-08-16 Datainnovation I Lund Ab System and method for automatic taking of fluid samples
US20060216209A1 (en) * 2005-02-14 2006-09-28 Braig James R Analyte detection system with distributed sensing
US20070083091A1 (en) * 2005-02-14 2007-04-12 Sterling Bernhard B Analyte detection system with reduced sample volume
US20060195046A1 (en) * 2005-02-14 2006-08-31 Sterling Bernhard B Analyte detection system with reduced sample volume
US7860543B2 (en) 2005-02-14 2010-12-28 Optiscan Biomedical Corporation Analyte detection system with reduced sample volume
US7860542B2 (en) 2005-02-14 2010-12-28 Optiscan Biomedical Corporation Analyte detection system with reduced sample volume
US9863837B2 (en) 2013-12-18 2018-01-09 OptiScan Biomedical Coporation Systems and methods for detecting leaks
US11426726B2 (en) 2018-04-02 2022-08-30 Dropworks, Inc. Systems and methods for serial flow emulsion processes
US11471886B2 (en) 2018-04-02 2022-10-18 Dropworks, Inc. Systems and methods for serial flow emulsion processes
US11471884B2 (en) 2018-04-02 2022-10-18 Dropworks, Inc. Systems and methods for serial flow emulsion processes
US11504710B2 (en) 2018-04-02 2022-11-22 Dropworks, Inc. Systems and methods for serial flow emulsion processes
US11833510B2 (en) 2018-04-02 2023-12-05 Dropworks, Inc. Systems and methods for serial flow emulsion processes
US11931736B2 (en) 2018-04-02 2024-03-19 Dropworks, Inc. Systems and methods for serial flow emulsion processes
US12364981B2 (en) 2018-04-02 2025-07-22 Dropworks, Inc. Systems and methods for serial flow emulsion processes

Also Published As

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DE2036262A1 (de) 1971-03-04
NL7010593A (enrdf_load_stackoverflow) 1971-01-27
FR2055585A5 (enrdf_load_stackoverflow) 1971-05-07
AU1737770A (en) 1972-01-13
CH514137A (de) 1971-10-15
GB1301556A (enrdf_load_stackoverflow) 1972-12-29
BE753912A (fr) 1971-01-25

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