WO1985005459A1

WO1985005459A1 - Apparatus for optical quench of a sample

Info

Publication number: WO1985005459A1
Application number: PCT/US1985/000915
Authority: WO
Inventors: Charles A. Keenan; Donald L. Horrocks
Original assignee: Beckman Instruments, Inc.
Priority date: 1984-05-21
Filing date: 1985-05-15
Publication date: 1985-12-05
Also published as: FI860290A; FI860290A0; JPS61502217A; EP0189438A1

Abstract

Apparatus for the optical quench of a sample (10) including a photodetector (12, 14), means for positioning the sample in an operative relationship with the photodetector, and a liquid crystal light valve (15) disposed between the sample and the photodetector when the sample is in the operative relationship. The light transmission characteristics of the liquid crystal light valve are varied in response to an attenuation signal generated by a power supply. The apparatus may further include means responsive to the photodetector means for generating a control signal and the power supply means may further be responsive to the control signal for varying the attenuation signal with respect thereto.

Description

APPARATUS FOR OPTICAL QUENCH OF A SAMPLE

Background of the Invention The present invention relates generally to liquid scintillation counting and, more particularly, to an appa¬ ratus for the optical quench of a sample.

The present application is related to copending app¬ lication Serial No. 61₂.1₈₂. entitled "Single Sample Quench Determination", filed concurrently herewith in the names of Donald L. Horrocks and Alfred J. Kolb, and assigned to the same assignee as the present application.

Liquid scintillation techniques are well known for measuring the activity of samples containing radionuc- lides. Such a radioactive sample, typically a beta emit¬ ter, is dissolved or suspended in a _*liquid scintillation medium. Nuclear disintegrations occurring in the sample produce visible light flashes or scintillations in the scintillation medium with the amount of light emitted from a scintillation being proportional to the energy of the corresponding disintegration.

A liquid scintillation counter measures the relative intensities of scintillations occurring ^■ in the liquid scintillation medium. Typically, scintillations occurring within the scintillating medium are detected ^'by a suitable photodetector which produces output pulses having pulse heights proportional to the intensity of the detected scintillations. The liquid scintillation counter counts the pulses in a plurality of pulse height channels or "windows" having, upper and lower pulse height limits that together span a predetermined range of pulse heights. The counts accumulated in each window may then be plotted with respect to corresponding pulse heights to provide a pulse

suEsτ; _M<^ *-*j **» ( * height spectrum representing the energy spectrum of the nuclear radiation emitted by the radioactive sample.

It is well known in the liquid scintillation art that materials present in the liquid scintillation medium can decrease the number of photons reaching the photodetector for a given nuclear disintegration in the liquid scintil¬ lation medium. For example, the production of photons in the scintillation medium may be decreased or emitted photons may be absorbed. Such effects are commonly re¬ ferred to as "quenching" and in each case result in the reduction of the number of photons which reach the photo¬ detector. In particular, some scintillation events which would be detected in an unquenched sample will fall below the photodetector detection threshold in a quenched sample and thus go undetected. The result is that the number of counts per unit time detected by the photodetector for a quenched sample is decreased as compared with an otherwise identical unquenched sample. The scintillation count rate detected in a quenched sample as compared with the disin- tegration...rate occurring within the sample is commonly referred to as "counting efficiency".

Quenching acts equally on all events produced by the same type of excitation particle, for example, electron (beta), alpha, proton, and so on. Thus, if quenching is sufficient to reduce the measured response for one disin¬ tegration by a given percentage, it will reduce all res¬ ponses by the same percentage. In a liquid scintillation counter, quenching results in a shift of the pulse height spectrum detected by the counter to lower pulse height values, which is commonly referred to as "pulse height shift".

Continuing efforts in the liquid scintillation art have been directed to measuring quench and relating quench to counting efficiency by means of a "quench curve" which plots counting efficiency with respect to the amount or degree of quench. The quench curve may then be used to correct the count rate of a sample for the effects of quench. In determining a quench curve, the quench of one or more samples is varied. For each degree of quench, the sample counts per unit time is measured for some predeter¬ mined portion of the pulse height spectrum. By dividing the counts per unit time for such portion of the pulse height spectrum by the disintegrations per unit time occurring in the sample, the efficiency for each degree of quench is determined. A quench curve is then constructed by plotting efficiencies determined as just described versus the measured degree of quench.

It is known in the art to vary the degree of quench by means external to the sample. As examples, U.S. Patent 3,688,120 discloses externally varying sample quench by either moving the photodetectors away from the sample or introducing mechanically driven variable aperture iris type lenses, between the sample and the photodetectors. The former technique, however, requires that shielding surrounding the counting chamber be enlarged to accom¬ modate the movement of the photodetectors, an important drawback where a compact, light-weight liquid scintilla¬ tion counter is desired. The latter technique also suffers from an important disadvantage, namely, the iris lenses mechanically obscure portions of the sample from the photodetectors, thereby optically quenching the sample in a nonuniform fashion.

Another example of an external quench device is illustrated in U.S. Patent 4,205,231 which discloses a controllably compressible cylindrical spring surrounding the sample vial. The spring acts as an adjustable light diaphragm according to the amount of spring compression. -4-

However, such a device again does not uniformly attenuate the scintillations occurring within the sample, resulting in nonuniform sample quench.

Summary of the Invention The apparatus of the present invention overcomes the disadvantages and drawbacks of the prior art and provides an apparatus for optical quench which is compact, easily placed between the sample and the photodetectors, which provides uniform attenuation and thus uniform quench, and which provides repeatable quench levels.

Toward the foregoing ends, an apparatus in accordance with the present invention includes a photodetector, means for positioning a sample in an operative relationship with respect to the photodetector, and a liquid crystal light valve disposed between the sample and the photodetector when the sample is in the operative relationship. The liquid crystal light valve, in response to an attenuation signal, varies its light transmission characteristic. A power supply provides the attenuation signal to the liquid crystal light valve.

The apparatus may further include means responsive to the photodetector for generating a control signal. The power supply is responsive to the control signal to there¬ by vary the attenuation signal and thus vary the attenua¬ tion of the liquid crystal light valve.

Brief Description of the Drawings Fig. 1 is a block diagram of a liquid scintillation counting system for practicing the method of the present invention. Fig. 2 is a graphical plot of pulse height distribu¬ tion spectra of a liquid scintillation sample at three varying levels of quench.

Fig. 3 is a graphical plot of log CP versus normal¬ ized values (R) of pulse height values PH.

Fig. 4 is a graphical plot of a quench curve deter¬ mined in accordance with the present invention.

Fig. 5 is a graphical plot of a pulse height spectrum for a radionuclide contained in an unknown sample wherein the DP of such sample for various portions of the pulse height spectrum are determined in accordance with the present invention.

Description of a Preferred Embodiment With reference now to Fig. 1, there is shown a liquid scintillation counting system in accordance with the pre¬ sent invention. The scintillation counting system is arranged ..to. measure radioactivity issuing from a sample generally indicated at 10 and comprising a vial disposed within a shielded counting chamber and containing a liquid scintillation medium and sample. A pair of photomulti- plier tubes (PMTs) 12 and 14 is arranged to detect and convert the scintillations of the sample 10 to correspond¬ ing output voltage pulses, each such pulse haying an amp¬ litude proportional to the photon intensity of the corres¬ ponding scintillation detected. The PMTs 12 and 14 pro¬ duce a pair of coincident output pulses for each detected scintillation.

Disposed between the sample 10 and the PMTs 12 and 14 is a sample optical quenching means 15. The quenching means 15 includes means for optically varying the apparent quench of the sample 10 as detected by the PMTs 12 and -6-

14. Advantageously, the sample optical quenching means 15 includes two liquid crystal light valves 15a and 15b dis¬ posed between the sample 10 and the PMTs 12 and 14, res¬ pectively. The light valves 15a and 15b variably attenu¬ ate the light from scintillations occuring within the sample 10 in response to an adjustable AC voltage from a controllable voltage source 15c of conventional design. In the embodiment disclosed herein, the adjustable voltage may be adjustable over a range of about 3 volts to 30 volts AC (rms), and may have a frequency in the range of about 30 Hz to 1000 Hz. The controllable voltage source 15c is in turn controlled by means of a control signal generated as is described hereinbelow. The liquid crystal light valves may be, for example, of a type CIN available from UCE, Inc., Norwalk, Connecticut. An example of a suitable commercially available power supply usable as the controllable voltage source 15c is a Model 3310A available 'from Hewlett-Packard Company.

With continued reference to Fig. 1, the output of each of-the- PMTs 12 and 14 is coupled as an input to a combined pulse summation circuit and amplifier 16, the output of which is an analog pulse. By summing coincident output pulses from the pair of PMTs 12 and 14, and thereby detecting a larger combined pulse than either output pulse alone, the system signal-to-noise ratio is improved. Moreover, the system resolution is improved, that is, the uniformity of response between two equal-energy events is improved.

The output of each PMT 12 and 14 is also coupled as an input to a coincidence circuit 18 which produces an output pulse upon receipt of essentially coincident input pulses. The outputs from the pulse summation and ampli¬ fier 16 and the coincidence circuit 18 are both applied to an analog gate 20 which passes the analog output from the - 7- pulse summation and amplifier 16 when the output pulse from the coincidence circuit 18 is also received by the gate 20. Thus, when a scintillation event within the sample 10 is detected by the PMTs 12 and 14, the coinci¬ dent pulses from such PMTs 12 and 14 are summed by the pulse summation and amplifier 16 and are applied to the gate 20. The coincident pulses from the PMTs 12 and 14 are also detected by the coincidence circuit 18 which applies a pulse to the gate 20. In the presence of the output pulse from the coincidence circuit 18, the analog output pulse from the pulse summation and amplifier 16 is passed by the gate 20.

The output of the gate 20 is applied to an analog-to- digital (ADC) logarithmic pulse height converter 22 which provides a digital output logarithmically proportional to the height of the analog pulse applied thereto. The digi¬ tal output of the ADC pulse height converter 22 is applied to a microprocessor-based control unit 24. The control unit 24 is of conventional design and includes a micro¬ processor--and related memory and input-output interface units, all well known in the art. The control unit 24 compares the value of the digial output from the ADC pulse height converter 24 to a ^"plurality of predetermined values which define a plurality of energy ranges or windows to¬ gether spanning a predetermined energy or pulse height range. According to the value represented by, the digital output from the ADC pulse height converter 22, the control unit 24 determines which window the digital value falls within and accordingly increments one storage location within a pulse height distribution storage area 26. The pulse height distribution storage area 26 includes a plur¬ ality of storage locations corresponding to the windows established by the control unit 24. As the liquid scin¬ tillation counting process is performed, the values stored in the various storage locations within the storage area -8-

26 together represent a pulse height distribution curve. The storage area 26 may comprise, for example, a portion of the memory accessible to and controlled by the micro¬ processor within the control unit 24, each storage loca¬ tion within such storage area 26 being cleared or reset prior to the start of a liquid scintillation counting procedure.

The control unit 24 also directs the positioning of the sample 10 within a counting chamber by a conventional sample positioning means 28. The control unit 24 further actuates conventional external standard positioning means 30 for selectively positioning an external standard source, such as a cesium-137 gamma source, in an operative position for irradiating the sample 10 to generate a Comp- ton pulse height spectrum. The control unit 24 also provides the control signal to the sample quenching means 15 and in the embodiment of Fig. 1 in particular to the controllable voltage source 15c. As described above, the degree of optical quenching of the sample 10 is varied in response -to_ the control signal from the control unit 24. As will be recognized by those skilled in the art, the control signal may be either analog or digital depending upon the particular circuitry within the variable voltage source 15c, all of which may be accomplished using conven¬ tional means.

The liquid scintillation counting system of Fig. 1 further includes a conventional display unit 32 such as a cathode ray tube (CRT) and a suitable input device such as a keyboard 34. The display unit 32 can display the count rate derived in a particular window or may display a curve graphically showing the pulse height distribution spec¬ trum. The display unit 32 also displays a pulse height value PH corresponding to an inflection point I on the Compton edge automatically located and determined as des- -9- cribed hereinbelow and as also described in U.S. Pat. 4,075,480 referenced above.

It will be recognized by those skilled in the art that the system of Fig. 1 is essentially a conventional multichannel liquid scintillation counting system or ana¬ lyzer modified in accordance with the teachings of the present invention. Such conventional multichannel analyz¬ ers are well known in the art such as, for example, the 5800 and 9800 series liquid scintillation counters avail¬ able from Beckman Instruments, Inc.

Turning now to a description of the operation of the apparatus of Fig. 1, such operation will first be briefly set forth. A more detailed description of such operation is then made with reference to Figs. 1-5.

Briefly, the apparatus of Fig. 1 optically varies the quench of the single sample 10. At various quench levels, the system measures the CPM of the sample within a window wide enough, to include all detected pulses produced by the sample, the CPM of the sample occurring within a predeter¬ mined window, sometimes referred to hereinafter as a "cal¬ ibration window", and the pulse height of a unique point on the pulse height spectrum when the sample is exposed to the standard source. The DPM of the single sample is then determined using the method of U.S. Patent 4,060,728 which is assigned to the assignee of the present application and which is incorpoated by reference herein. For each CPM measurement within the calibration window, the efficiency is determined by dividing such CPM by DPM. A quench rela¬ tionship may then be generated by relating efficiency of each such CPM measurement to an indication of quench for each such measurement. As just described, a single sample in accordance with the method of the present invention uniquely yields a quench relationship or curve from a single sample without destroying the sample or relying upon DPM determined by pipetting a calibration standard into the sample. Furthermore, the DPM for an unknown sample may be determined using the quench relationship uniquely developed as just described. To do so, the CPM within the calibration window and quench are measured for the unknown sample. Having determined the quench, the efficiency for such sample is determined from the quench relationship. The DPM for the sample may then be found by dividing the CPM by the efficiency.

Turning now to a more detailed description of the operation of the system of Fig. 1 and the method of the present invention, the control unit 24 begins by command¬ ing the sample positioning means 28 to position the sample 10 within the counting chamber adjacent the PMTs 12 and 14. The control unit 24 also adjusts the sample optical quenching means 15 for a first amount of quench which, in the embodiment disclosed herein, is a minimum amount of quench. In particular, the control unit 24 generates the control -signal that is applied to the controllable voltage source 15c to thereby control the output of the voltage source 15c such that the valves 15a and 15b provide a minimum of optical attenuation. The control unit 24 com¬ mands the standard source positioning means 30 to position the standard source into an operative position adjacent the sample 10 for irradiating the sample 10. , he system counts the pulses from the PMTs 12 and 14 in a plurality of counting windows to determine the counts developed for both the standard source and the sample. The control unit 24 commands the standard source positioning means 30 to remove the standard source from its operative position to an inoperative position where the standard source does not contribute to the scintillations occurring within the sample 10. The system again counts pulses from the PMTs 12 and 14 in a plurality of counting windows to determine -li¬ the counts developed for the sample alone. The net counts developed in response to standard source are then deter¬ mined for the various counting windows by subtracting the counts obtained for the sample alone from the counts obtained for both the standard source and the sample. Such net counts are used to plot a standard source pulse height curve 50 as seen in Fig. 2.

The control unit 24 determines a unique point on the pulse height curve which in the preferred embodiment is the inflection point I-_j_ of the curve 50. A preferred method for locating such inflection point of the Compton edge, that is, where the second derivative of the edge is zero, is described in U.S. Patent 4,075,480 which is in¬ corporated herein by reference. Briefly, the inflection point is located by counting in a plurality of windows along the Compton edge and by calculating the second deri¬ vative (that is, the slope of the slope of the edge) at spaced points along the edge by subtracting the counts of adjacent counting windows. When a group of two spaced derivatives, is obtained, one positive and one negative, the inflection point is thus determined to be between the locations of the two derivatives. Thereafter, conven¬ tional interpolation techniques are employed to determine the exact location of the inflection point I_]_ between the derivative values. When the inflection point is located, the corresponding pulse height value PH*_j_ is determined by the control unit 24 and may be displayed, for example, on the display unit 32.

With PH^*j_ determined and the standard source removed from its operative position to its inoperative position, the control unit 24 adjusts the lower and upper window limits corresponding to a selected storage location within the storage area 26 to establish a window W (Fig. 2) wide enough to include all the pulses issuing from the sample -12-

10 alone. More particularly, the lower limit of the win¬ dow W is set at zero plus height while the upper limit of the window W is set a sufficient distance outward on the pulse height axis so that the window W includes all of the pulses issuing from the sample alone. As seen in Fig. 2, the sample alone may have a pulse height spectrum 52 which is completely included within the window W. The count rate for the sample alone within window W is designated CPM*_j_. It will be understood that the control unit 24 may sum the contents of the storage locations within the stor¬ age area 26 which together span the window W rather than readjusting the upper and lower window limits for a selec¬ ted storage location as just described. In either case, the control unit 24 operates such that the system of Fig. 1 counts all of the pulses issuing from the sample alone, i.e. CPM_]_.

The sample is also counted within a predetermined or calibration window to provide a^"value CP_MC-_]_. The calibra¬ tion window may be selected b -the user and determines the window t-ha-t-will be represented by the efficiency curve developed as described below. If the calibration window is set equal to the window W, then CPM*_j_ = CPMC^*j_.

With PH-L, CPM*-_ and CPMC^ determined as just des¬ cribed, the control unit 24 varies the control signal applied to the sample optical quenching means- 15 so as to vary the optical quench of the sample 10. In the embodi¬ ment disclosed herein, the control signal is applied to the controllable voltage source 15c, causing the output of the voltage source 15c to vary and correspondingly in¬ crease the attenuation of the liquid crystal light valves 15a and 15b, thereby increasing the optical quench of the sample 10. The control unit 24 again positions the stan¬ dard source first in an operative relationship and then in an inoperative relationship with the sample 10, determines -13- a second unique point I2 on a second curve 54 (Fig. 2), and counts the sample 10 alone in the window W, all in a manner as previously described. With increased optical quench, a pulse height curve for the sample 10 above is as shown by curve 53 of Fig. 2.

The system of Fig. 1 repeats the steps just described for varying degrees of optical quench, thereby generating a plurality of unique pulse height values PH^*j_-PH_n and corresponding CPM and CPMC values, CPM-j_ through and in¬ cluding CPM_n and CPMCJL through and including CPMC_n. One such value PH3 may correspond to an inflection point I3 on a third curve 56 as seen in Fig. 2. The sample 10 alone may have a pulse height curve 58 for the degree of quench represented by PH3.

With the pulse height, CPM and CPMC values so deter¬ mined, the DPM for the sample 10 is determined in accord¬ ance with the teachings of U.S. Patent 4,060,728 which is incorporated herein by reference. As taught therein, the pulse heigh_t values are normalized with respect to some selected common pulse height value to provide a plurality of normalized values R*_j_ through and including R_n for the corresponding pulse height values.

After developing the normalized pulse height values R]_ through and including R_n, the values of R are correla¬ ted with corresponding pulse counts CPM*_j_ through and in¬ cluding CPM_n as by graphically plotting log CPM with res¬ pect to R as illustrated in Fig. 3. The intercept of the plot with the log CPM axis (that is, log CPMn for R = 0) establishes the logarithm of the sample DPM rate. Thus the antilog of such a value determines the sample disin¬ tegration rate or DPM. -14-

A quench relationship or quench curve in accordance with the present invention may now be determined. As is readily apparent, the quench relationship or curve is de¬ rived from a single optically quenched sample, providing advantages heretofore unattainable in the art. For each CPMC value measured as described above, a corresponding efficiency is determined by dividing CPMC by DPM. If efficiency is to be expressed in percentage, the result of the division is multiplied by 100.

For each such efficiency value, a corresponding quench representation is also determined. In the embodi¬ ment disclosed herein, such quench representation is re¬ ferred to as an H number. The H number for each CPMC value and corresponding efficiency is found, in a system where pulse height is related to log energy, by subtract¬ ing the unique pulse height value corresponding to the CPM value from a reference pulse height value, PH₀. The ref¬ erence pulse height value PH₀ is preferably obtained using a sealed unquenched sample as is known in the art. It is to be noted., however, that any one of the pulse height values could be used as a reference. Thus for CP C2_. a corresponding efficiency is obtained by dividing CPMC2 by DPM and multiplying by 100. The corresponding quench indication is found by subtracting PH2 from PH^* _|_ (Fig. 2). The resulting quench representation is H2.

Similarly, efficiencies and quench indications are determined for the remaining values of CPMC determined above, that is, CPMC₂ through and including CPMC_n. Effi¬ ciency is then plotted with respect to quench indication (H number) to provide a quench relationship or curve 60 as seen in Fig. 4. Thus, the method in accordance with the present invention enables the determination of the quench curve 60 (Fig. 4) from a single sample using optical quen¬ ching. In a further aspect of the present invention, the quench curve 60 may be used to determine DPM for an un¬ known sample. As an example, the system of Fig. 1 may be operated as described above to determine a pulse height value along the Compton edge PH_U and a CPMC value for the predetermined window previously used to determine effi¬ ciency, that is, the calibration window. For example, the unknown sample when counted alone may yield a pulse height curve 62 as shown in Fig. 5. With the sample exposed to the standard source, the Compton edge inflection point may correspond, for example, to a pulse height PH_U of 700. With a standard unquenched pulse height PH_U of 835, the H number is τ>E₁ - PH_U, or 835 - 700 = 135. Using the uni¬ quely derived quench curve 60 of Fig. 4, the H number of 135 corresponds to an efficiency of 40%. Thus, the CPMC for the calibration window may be corrected to yield DPM by dividing the CPMC for the calibration window by percent efficiency and multiplying the result by 100. For exam¬ ple, the CPMC within the calibration window for the un¬ known sample is 100,000. Consequently, DPM for the unknown sample is 250,000.

While a preferred embodiment of the present invention has been described in detail herein, modifications and changes may be made without departing from the spirit of the present invention as defined by the appended claims.

Claims

-16- What is claimed is:

1. An apparatus for the optical quench of a sample, comprising:

photodetector means;

means for positioning the sample in an operative relationship with respect to the photodetector means;

a liquid crystal light valve disposed between the sample and the photodetector means ^'when the sample is in the operative relationship, the liquid crystal light valve varying its light transmission characteristics in response to an attenuation signal; and

adjustable power supply means for generating the attenuation signal and including means for controllably varying the attenuation signal. .

2. An apparatus as in claim 1, wherein the apparatus further includes means responsive to the photodetector means for generating a control signal and the power supply means includes responsive to the control signal for con¬ trollably varying the attenuation signal in response to the control signal.

3. An apparatus as in claim 1 wherein the photode¬ tector means comprises two photodetectors, the first named liquid crystal light valve being disposed between one of the photodetectors and the sample when the sample is in the operating relationship so as to intercept light pass¬ ing from the sample to such one photodetector, and the apparatus further includes a second liquid crystal light valve disposed between the other of the photodetectors and the sample when the sample is in the operational rela¬ tionship so as to intercept light passing from the sample -17- to such other photodetector, the second liquid crystal light valve varying its light transmission characteristics in response to the attenuation signal.