Patent GB-1007224-A (GB)
Title: Method and apparatus for performing multiple analysis
IPC: G01N35/08
Filed: 1963-01-23
Abstract: 1,007,224. Photo-electric analysis. TECHNICON INSTRUMENTS CORPORATION. Jan. 23, 1963 [Jan.23, 1962; Oct. 31, 1962], No. 2846/63. Heading G1A. [Also in Division B1] . In an arrangement for the quantitative analysis of a fluid sample having a plurality of known ingredients a like plurality of sample streams is formed each being treated for analysis in respect of a different ingredient and the quantitatively analysed separately during the flow of the treated streams. The invention, which has a general application, is described in connection with the analysis of body fluids e.g. blood or blood serum, in respect of such substances as albumin, total protein, chlorides, carbon dioxide, sodium, potassium, glucose and blood-urea-nitrogen. Known colorimetric and spectral-flame photo-electric analysing techniques are employed the analysis being effected sequentially in respect of the different substances and the results recorded. Fig. 1, shows one embodiment in which a take-off device 18 connected to aspirating tubes 20, 22 of a proportioning pump 24 (preferably of the kind disclosed in Specifications 817,070) withdraws a portion of fluid from one of a number sample cups 16 held in a rotary sampler device 14 (preferably of the kind disclosed in Specification 834,635) the arrangement being such that when a desired quantity of fluid has been withdrawn the take-off device 18 is inserted in another cup 16 and supplies the apparatus with a different sample separated from the first sample by an intervening air segment. Considering any one sample the operation of the apparatus is as follows. The portion of the sample withdrawn by pump tube 20 is combined in a fitting 28 with air (or inert gas), fed to tube 30, and with a liquid stream containing acidifed lithium nitrate, fed to tube 32, the air or inert gas serving to break up each sample into a number of liquid segments spaced by air segment which help maintain the tubes of the apparatus clean and prevent contamination of one sample by a preceding sample and the acidified lithium nitrate providing an internal standard for that portion of the sample which is to undergo spectral-flame analysis. This segmented liquid stream is fed via conduit 34 to one side, the sample is side, of a dialyzer 36 (preferably of the kind disclosed in Specifications 827,925 and 827,927) comprising plates 38a, 38b separated by a membrane 40 which operates to separate portion of the diffusible substances from the non-diffusible substances the former diffusing into a recipient stream comprising water and segmentising air supplied via respective pump tubes 44, 46 and fed over conduit 42 to the recipient side of the dialyzer from which it flows via conduit 48 whilst the non-diffusible substances flow from the sample side through a conduit 50. The (crystalloid) substances which diffuse into the recipient stream in conduit 48 comprise, blood-urea-nitrogen, glucose, sodium, potassium and chlorides (as well as a portion of the lithium nitrate) and to effect the required quantitative analysis the stream in conduit 48 is divided into separate streams by means of conduits 52,54,56,58 connected to respective tubes of pump 24. In the case of conduit 52 pump tube 146 operates to supply the stream to a fitting 144 which also receives via mixing coil 156 and a fitting 154 a segmentized colour-producing reagent stream formed by introducing colour-producing reagents suitable for the quantative analysis of the blood-urea-nitrogen content into pump tubes 148, 150 and a segmentizing fluid into pump tube 152 the combined streams being fed to a further mixing coil 158 and thence via a heating bath 162 to a debubbler 76f which removes the segmentizing fluid and supplies a consolidated liquid stream to the flow cell 80e of the colorimeter 82. In similar manner the stream in conduit 54 is segmentized and treated for analysis of the glucose content and supplied via heating bath 142 to flow cell 80d, that in conduit 58 being segmentized and treated for analysis in respect of the chloride content and fed to flow cell 80b whilst the streams in conduit 56, which, because of the presence of the lithium nitrate internal standard, does not require further treatment, is fed via debubbler 76d to the spectral flame photometer 60, the latter (preferably of the kind disclosed in App. 29969/60 Serial number 946689) having provision for effecting analysis in respect of both the sodium and potassium content. The flow through the sample side of the dialyzer via conduit 50 containing the colloidal substances as well as the remaining portions of the crystalloid substances is divided into two streams in respective conduits 64, 66, that in the former being segmentized and treated for analysis in respect of its total protein content and supplied to flow cell 80a whilst that in conduit 66 is treated for analysis of its carbon dioxide content (released by the acid content of the acidified lithium nitrate) by introducing a suitable anti-foam reagent via pump tube 104 and conduit 106 and supplying the resulting stream through a mixing coil 108 to a gas-liquid separator 110 (preferably as disclosed in Specification 909,415) the output of which is combined in pump fitting 116 with a suitable colour producing reagent introduced via pump tube 118 to provide a resultant stream for flow cell 80c, any remaining carbon-dioxide being removed by debubbler 76c. For the remaining analysis, that of the albumiun content, the sample is taken via conduit 26 (to avoid the adverse effects which the lithium nitrate introduced via pump tube 32 would have on the colorimetric treatment for albumiun) and after segmentizing and suitable colorimetric treatment via respective pump tubes 70, 68 is supplied via mixing coil 74 and debubbler 76 to flow cell 80. The flow cells (two 'spares' 80f, 80g being shown) are mounted on a carriage 178 (see also Fig. 2) which moves under the control of a reversing motor 188 driving a Geneva mechanism 192 and controlled by a timer 190 such that the cells are positioned in succession and for predetermined periods of time in the path of a light beam L co-operating with a measuring photo-electric device 174 (a photovoltive or photoconductive cell) and a similar reference device 172 (shown only in Fig. 1). When all the flow cells have reached the measuring position the carriage actuates a switch 202 which causes the motor 188 to reverse direction to drive the carriage in the opposite direction until the latter actuates switch 204 operation of which again reverses the direction of the motor which then drives the carriage in the first direction until the circuit to the motor is interrupted by switch 236 controlled by the Geneva mechanism. The apparatus is now in position to commence a second cycle when switch 216 is closed. Alternatively, the flow cells may be stationary and the light source and photo-electric devices arranged to move with respect thereto. In operation, the outputs of the photo-electric devices including devices 180,184, and 182, 186 comprising the reference and measurement photoelectric devices associated respectively with the spectral-flame analysis of the sodium and potassium contents are fed sequentially to the recorder control circuit 168 by means of switches 176 operated by shaft 308 driven in step with the movement of the carriage via rack-and-pinion 302, 304 (Fig. 2) the sequence being such that the various streams are examined in the order in which the colour reaction is completed this being aided by giving appropriate lengths to the flow paths between the pump and the various flow cells. In the case of Fig. 1, the flow cells are examined in the order shown except that the measurements of the sodium and potassium contents occur in the fifth and sixth positions thus producing a recording as shown by the trace 300 (Fig. 4). The recorder 166 and its control circuit 168 (which are of the type described in Specification 874,855) are described with reference to Fig. 3 (not shown) and generally comprises a null-type current ratio-balancing system to which the outputs of the measuring and reference photo-electric devices are supplied via banks of gauged switches driven in step with the switch banks 176 (Fig. 1). Additionally, means are provided to allow the use of linear ordinate scales in the case of recordings produced by colorimetric analysis, since in the latter case a logurithmic relationship exists between the concentration of the substance and the light transmission, and in the case of substances (e.g. glucose, carbon dioxide, sodium and potassium)for which the photo-electric response increases with increase in concentration of the substance a polarity traversing means for the output of the photo-electric devices is provided. Means are also described for calibrating the apparatus using substances of known concentrations the calibrations being printed on the chart (Fig. 4) either prior to use or concurrently therewith by the provision of printing plates produced from the calibration and secured to the recorder in position for printing the chart paper as it moves through the recorder. Each printing plate may be formed as a stretchable strip having equally spaced concentration numeral values so that the maximum and minimum values may be correctly positioned for each scale. The normal ranges for the concentration of each substance may be indicated by shaded areas 392. In a modification of the embodiment of Fig. 1 the colorimeter comprises stationary flow cells each provided with a light source and a measuring and reference photoelectric device (Fig. 5, not shown). In both embodiments the recorder maybe of the type which prints the actual numerical values of the concentration instead of employing a stylus to draw a curve. The colorimeter comprises the carriage number 178 (see Figs. 6 and 7) which is movable, as described in connection