1a. A Zener diode D2a is coupled between source and gate terminals of the transistor Q1a and a biasing resistor R₀a is coupled between the gate electrode and ground potential.

The controller 24 develops a control signal that is supplied in non-inverted form to an enable/disable device or circuit 30a. In one embodiment, the enable/disable device or circuit 30a comprises a phototransistor or other opto-coupler that isolates the controller 24 from the high voltage of the DC power source 22a.

The switching circuit 28b includes transistor Q1b, diode D1b, Zener diode D2b, biasing resistor Rob, and enable/disable device or circuit 30b, wherein the element 30b receives the control signal developed by the controller 24 in inverted form.

Referring to FIG. 3, in the simplified illustrated embodiment, the PMT circuit 26 comprises a PMT 31, a voltage divider circuit 32 comprising a plurality of resistors R₁, R₂, . . . , R_Ncoupled to one another and further coupled across adjacent dynodes 34 of the PMT 30, capacitors C₁, C₂, . . . , C_Mcoupled across some of the resistors R₁, R₂, . . . , R_Nof the voltage divider circuit 32 and a load resistor R_Loadcoupled between an anode 36 of the PMT 31 and ends of the resistor R_Nand capacitor C_M. It may be noted that R_Loadmay instead be realized by electronic circuitry, such as an integrator or a transimpedance amplifier, if desired. An output of the PMT circuit 26 is developed across the load resistor R_Load. A photocathode 38 of the PMT 31 and the load resistor R_Loadare coupled to negative and positive voltage potentials, −HV and ground, respectively, of one of the high voltage DC power sources 22a, 22b, as described in greater detail hereinafter.

The controller 24 is preferably a programmable device of any suitable type that executes programming, for example, as shown in FIG. 4 or 6, responsive to the output signal of the PMT circuit 26. Specifically, FIG. 4 illustrates a flowchart of programming for operating the measurement system 20 of FIG. 2 whereas the flowchart of FIG. 6 represents programming for operating the circuit of FIG. 5 as described in greater detail hereinafter.

Referring to FIG. 4, following system energization, a block 100 senses the outputs of the DC power sources 22a, 22b and delays further execution of programming until the outputs of the power sources 22a, 22b have sufficiently stabilized. In some embodiments, the block 100 may wait until a particular period of time has elapsed for the outputs to sufficiently stabilize. Once the DC power source outputs have stabilized, a block 102 energizes the illuminant source (e.g., a flash lamp) and moves the measurement head to a position proximate a first measurement well. Thereafter, a block 104 couples a first selected one of the DC power sources 22, in this case the DC power source 22a, to the PMT circuit 26. This is accomplished by providing, for example, a high state control signal to the enable/disable device or circuit 30a, thereby turning the transistor Q1a on at a first time. This, in turn, couples the −500 volt DC power source 22a to the PMT circuit 26. Also, the supply of the inverted control signal to the enable/disable device or circuit 30b turns the transistor Q1b off also at the first time so that the DC power source 22b is decoupled from the PMT circuit 26.

A block 106 then operates the PMT circuit 26 to obtain a first measurement voltage magnitude resulting from sensing of the product sample following the first time. The first measurement may comprise a partial or full measurement operation, as desired. A block 108 evaluates the first measurement voltage magnitude to determine whether a characteristic of the first measurement is within a selected threshold range (in the description herein, descriptions of measurements and ranges reference the absolute magnitudes of signals and ranges). For example, the block 108 may compare the first measurement voltage magnitude across the load resistor R_Loadto a selected threshold range between zero and a selected threshold limit. The threshold limit may be selected in dependence upon a sensitivity versus supply voltage characteristic or other characteristic of the PMT 31. In a particular embodiment the selected threshold limit is approximately 0.9% of the full-scale measurement range of the PMT circuit 26. The full-scale measurement range may be of any suitable magnitude, for example, four orders of magnitude.

If the block 108 determines that the first measurement voltage magnitude is within the selected threshold range a block 110 switches the state of the control signal to selectively couple the DC power source 22b to the PMT circuit 26 and selectively decouple the DC power source 22a from the circuit 26, wherein the block 110 is operable at a second time subsequent to the first time. This combined function of the blocks 108, 110 permits a subsequent second measurement to be obtained with the −1000 volt DC power source 22b coupled to the PMT circuit 26 while ensuring that the PMT circuit 26 is set to a higher sensitivity in order to generate a more precise signal across R_Load. Further, because the output voltage of the −1000-volt DC power source 22b is already stable, switching from the −500-volt DC power source 22a to the −1000-volt DC power source 22b does not require any wait time for the voltage generated by the −1000-volt DC power source to stabilize. On the other hand, if the block 108 determines that the first measurement voltage magnitude is not within the selected threshold range the state of the control signal remains unchanged such that the DC power source 22a remains coupled to the PMT circuit 26 and the DC power source 22b is decoupled therefrom at the second time. The decoupling of the DC power source prevents an overflow condition of the ADC 21.

Following the blocks 108 and 110, control passes to a block 114, which operates the PMT circuit 26 to obtain a second measurement voltage magnitude resulting from sensing of the product sample at a time after the second time. Alternatively, the block 114 may obtain any number of third, fourth, fifth, etc. additional measurements of each sample using the same DC power source used for the second measurement and the measurements may be averaged to increase measurement accuracy.

Referring again to FIG. 4, in the illustrated embodiment the second measurement voltage magnitude is stored in a table by the block 114 and a block 118 then checks to determine whether product samples in all of the wells have been sensed (the second measurement of each product sample may be undertaken a single time or multiple times). If not, control returns to the block 104 so that the DC power source 22a is again coupled to the PMT circuit 26 so that additional first and second measurements are obtained. Once first and second measurements of product samples in all wells have been obtained, a block 120 causes the second measurement voltage magnitudes to be tabulated and/or displayed and the process ends. Alternatively, control may return to the block 102 for additional measurements if kinetic measurements are to be obtained.

In some embodiments, the illuminant source may be energized before the second measurement is undertaken by the block 114. Further, in some cases the energization of the illuminant source may be undertaken concurrently with or shortly after coupling of the DC power source 22b by the block 110.

The system 20 couples a second selected one of the DC power sources 22a, 22b to the PMT circuit 26 based upon a first sample measurement, which can be detected and evaluated in a brief period of time much shorter than the time required by a single high voltage DC power source 22a, 22b to settle when switching between levels. Further, selection of one of the DC power sources 22a, 22b to couple to the PMT circuit 26 based on an evaluation of the first sample measurement allows second measurement of wide dynamic range signals in an efficient manner that permits maximum measurement sensitivity, and/or resolution, and/or accuracy.

FIG. 5 illustrates a further embodiment similar to the foregoing embodiment in which one of three (or more) high voltage DC power sources, such as DC power sources 22a, 22b, 22c, are selectively coupled by switching circuits 28a, 28b, 28c to the PMT circuit 26 under the control of the controller 24 based upon a first product sample measurement. In the illustrated embodiment of FIG. 5, the DC power sources 22a and 22b develop voltage levels of −500 and −1000 volts, respectively, and the DC power source 22c develops an intermediate voltage level of −750 volts. Also, in the embodiment illustrated in FIG. 5, each of the switching circuits 28 is identical to the switching circuits 28a and 28b of FIG. 2, and the controller 24 and the PMT circuit 26 of FIG. 5 are identical to the controller 24 and PMT circuit 26, respectively, of FIG. 2, except for the programming described below.

FIG. 6 illustrates programming executed by the controller 24 in connection with the embodiment of FIG. 5. The flowchart of FIG. 6 includes the blocks 100, 102, 106, 114, 118, and 120 of FIG. 4. The block 104 is replaced by a block 204 that is operable at the first time to couple a first selected one of the DC power sources 22, in this case the −500 volt DC power source 22a, to the PMT circuit 26 and decouple the −1000 volt and −750 volt DC power sources 22b, 22c from the PMT circuit 26. Once the first measurement voltage magnitude is obtained by the block 106 after the first time control passes to a block 208, which evaluates the first measurement voltage magnitude to determine whether such measurement magnitude is at within a first selected threshold range T1. If this is the case, control passes to a block 210 operable at the second time to couple a second selected one of the power sources 22, in the illustrated embodiment, the −1000 volt DC power source 22b, to the PMT circuit 26. On the other hand, if the block 208 determines that the voltage magnitude of the first measurement is outside the threshold range T1, then a block 211 checks to determine whether the voltage magnitude of the first measurement is within a second selected threshold range T2. If this is found to be the case, a block 213 instead couples the PMT circuit 26 to a different second selected one of the power sources 22, specifically, in the illustrated embodiment, the −750 volt DC power source 22c, and decouples the PMT circuit from the −500 volt and −1000 volt DC power sources 22a, 22b, respectively.

Control from the blocks 210 and 213, and from the block 211 if such block determines that the first measurement voltage magnitude is outside the second selected threshold range T2, passes to the block 114.

Like in the previous embodiment, the selected threshold ranges T1 and T2 may be selected in dependence upon a sensitivity versus supply voltage characteristic or other characteristic of the PMT 31. In a specific embodiment the threshold range T1 may comprise zero to approximately 0.9% of the full-scale voltage magnitude of the PMT circuit 26 and the threshold range T2 may comprise zero to approximately 9.0% of the full-scale voltage magnitude of the PMT circuit 26. As in the previous embodiment, the threshold ranges T1 and T2 are selected so that overflow of the analog-to-digital converter 21 of the controller 24 as a result of the second measurement is avoided.

In terms of settling speed it may instead be advantageous in the embodiment of FIGS. 5 and 6 to obtain the first measurement by coupling the intermediate voltage (i.e., −750 volts) to the PMT circuit 26 and to transition to −1000V or −500V or remain at −750 volts for the second measurement. Still further, in other embodiments, one could alternatively obtain the first measurement using another of the DC power sources, such as the −1000 volt DC power source 22b, compare the first measurement to appropriate range(s), and either transition to another of the DC power sources or use the same DC power source based upon the comparison to obtain the second measurement.

In general, as should be evident from the foregoing, any number of DC power sources 22a, 22b, . . . , 22Z and switching circuits 28a, 28b, . . . , 28Z could be provided and operated by the controller 24 to couple selectively one of the DC power sources 22 to the PMT circuit 26. The choice of which DC power source 22 to couple to the PMT circuit is dependent upon one or more first measurement(s) and the characteristic(s) of the PMT 31 and/or the circuit 26, such as measurement sensitivity and/or measurement resolution and/or measurement accuracy, and/or a desirable balance thereof, as a function of detected magnitude of the first measurement. A fast, real-time acquisition of product sample measurements over an extended dynamic detector range can be achieved. Thus, in certain embodiments, for example, a settled voltage change between maximum and minimum voltage levels may be achieved within a few milliseconds (e.g., 5 milliseconds) or less, which may result in a desirable increase in an illuminant flash rate of the light source. This solution reduces the measurement time by 50% in relation to currently used methodology. This is desirable also for long term kinetic measurements of multiple samples and enables high throughput screening methods within the microplate reader range. Measurements can be obtained at constant time intervals independent of sample concentration. Any number of third, fourth, fifth, etc. additional measurements may be taken for each sample using the same DC power source used for the second measurement and the measurements may be averaged and tabulated to increase measurement accuracy.