Patent GB-1424823-A (GB)
Title: Apparaut sor measuring constituent concentrations in a sample by ab apparatus for measuring constituent concentrations in a sample  by absorption photometry
IPC: G01N21/25
Filed: 1973-02-06
Abstract: 1424823 Measuring concentration photo-electrically KIESS INSTRUMENTS Inc 6 Feb 1973 [8 Feb 1972 30 Nov 1972] 5743/73 Heading G1A [Also in Division H3] The constituent concentration of a test sample is measured by absorption photometry in a given wavelength range of applied light for each consituent analyzed, by determining the intensity of light transmitted along a path both in the absence and presence of the sample, calculating the difference in the logarithmic values of the signals to represent the concentration of the constituent of the sample, and providing a digital output representative of the difference. The invention is applied to a multi-function biochemical constituent concentration analyzer which utilizes a filter wheel to provide light of a wavelength suitable for a particular test. The light is passed through a test chamber to a photo-cell the output of which is applied via a preamplifier to a logarithmic converter which interacts with a control unit to produce start and stop signals to gate clock pulses to a digital up-down counter. The analyzer is constructed so that with the chamber empty a first (up) count is made and then the sample cuvette is introduced and a second (down) count is made in the reverse direction, the resulting difference count being displayed. The filter used is selected and the parameters of the measuring circuit are controlled by means of programming components, the particular set used being selected by an array of pushbuttons, so that the displayed count is a direct reading of the component concentration. The analyzer is also arranged to provide a prothrombin test. As shown, Fig. 4, the top of the analyzer is provided with two rows of test selection buttons 122B each of which is arranged to programme the analyzer by connecting into the ciruit components mounted in plug-in modules 122A which are also provided with selectively illuminable legends to indicate the test function selected. A heated incubator 130 is provided with recesses 130A for cuvettes awaiting test and also smaller recesses 130B for prothrombin test cuvettes and a prothrombin test station 130C. Inside the casing is arranged a lamp 144 emitting light which is collimated by a lens 150 before application to an interference filter, a plurality of which are carried on a filter wheel 152. The resulting monochromatic light is focused by lens 154 through a test chamber 156 to a photo-cell 158. In the measuring circuit, Fig. 6, the output current of the photo-cell 158 is linearly converted to a voltage by a preamplifier 204 the gain of which is determined by means of programming resistors R1, R2 under control of a gain transfer switch 208. The output of the preamplifier is compared with the value of an exponential ramp generated in logarithmic converter 210. The ramp is initiated by a control signal SCS from a control circuit and when it becomes equal to the amplified photo-cell signal an output SCS2 is produced. The time interval between the start and the end of the ramp is proportional to the logarithm of the photo-cell signal and during this interval clockpulses from an oscillator 222, the frequency of which is controlled by a resistor RC, are gated to an up-down counter 214. The programme modules 122 contain resistors R1, R2 and RC which are selectively connected into the circuit by the appropriate test button switch and also a fourth resistor RS which is connected to a servo-control system which positions the filter wheel to place the correct interference filter in the radiation path. The control ciruit is provided with count-up and count-down input controls 218, 220 and also receives an input from the separate prothrombin time circuit 234. Operation. The main test chamber is provided with three micro-switches which are operated in turn by the insertion of a cuvette into the chamber, the switches providing count-up, gain-transfer and count-down functions respectively. When a test function has been selected a cuvette containing the sample mixed with a suitable reagent is inserted into the test chamber. As the end of the cuvette operates the first (count-up) micro-switch a first measurement is taken the optical channel being open at this stage. The gain of the preamplifier 204 is determined by a first resistor R the value of which is selected so that the resulting count is normalized to that which would result from a measurement using a cuvette containing a reference solution (e.g. distilled water). As the cuvette is inserted further into the chamber the second micro-switch is operated to insert resistor R2 into the circuit in place of resistor R1. When thee cuvette is fully inserted so that it fills the optical channel the third (count-down) micro-switch is operated initiating a second measurement the counter operating in the down mode so that this count is subtracted from the first the resulting difference count being a direct measure of the concentration of the component for which the test is made. The frequency of the clock 222 is controlled to give a suitable "full scale" count in the time interval provided by the particular test filter used. The counter is connected to a digital display 216 which is blanked until the end of the second measurement. The programme module may also include components (diodes) to determine the position of a decimal point in the display and to reverse the order of the up and down counts if the particular test involves a reduction in absorption with increased component concentration. Prothrombin test, Fig. 11. A separate exciter lamp and a photo-cell 134 utilizing an appropriate filter are provided for the prothrombin test cavity which has a single micro-switch 270 which is closed on insertion of a cuvette containing a thromboplastin-calcium mixture. This resets the counter and prepares the control circuit for the measurement. The photo-cell is connected via a preamplifier 234C to a differentiating circuit comprising capacitor 234F, Resistor 234E and operational amplifier 234D. Resistor 234C and capacitor 234H form a low pass filter to reject unwanted noise and spurious flunctuations in sample transmittance. The differentiated signal is compared with a reference level by means of comparator 234K which produces an output pulse when the reference level is exceeded. When a citrated blood plasma sample is added to the cuvette the sudden - change in transmissivity is detected and initiates the counting of 10Hz clockpulses obtained from the power supply. As the clot begins to form the differentiated signal exceeds the reference level and a pulse is produced to terminate the count. The display, which is not blanked during the count, gives a direct reading of the prothrombin time to the nearest tenth of a second. In order to prevent early termination of the count due to perturbations produced when the plasma sample is added to the cuvette the control circuit is inhibited for four seconds after the start of the count by a suitable logic output 214C derived from the counter 214. The main control circuit is arranged so that operation of the count-down switch before the upcount has finished produces a special display, e.g. dashes in each indicator position. This indicates that the insufficient light is being received by the photo-cell to operate the log converter e.g. due to a lamp failure or incorrect filter position. The detector may comprise a blue enhanced Si photovoltaic cell provided with an IR cut off filter.