CN1204403A - Ultralow background multiple photon detector - Google Patents

Abstract

An ultralow background multiphoton detector device for radioisotopes (20) has a background of about one count per day and can detect one attomole of material. Two opposed gamma and X-ray photon detectors each preferably include a scintillation crystal (22) and a photomultiplier tube (26). Sandwiched between the detectors are a separator (32) and a sample holder (34) for a sample (36) labelled with a radioisotope such as I<125>. Each detector converts emissions from the radioisotope into electric output pulses in a base (30) which pulses are then subjected to signal processing for pulse shape analysis, discrimination of coincident from non-coincident events, and quantification of the radioisotope. Detector materials and components are selected to minimize background, and are shielded from external radiation in a composite shield (55). Detectors operating on different principes and sample holders of different configurations may be used. The device may further be constructed to resolve and provide images of two-dimensional sample arrays.

Description

The photon detector of ultralow background

The present invention relates to the multi-photon radioisotope detector of ultralow background.These detectors can quantitative measurment meet gamma-rays and X ray from what electron capture (EC) isotope emitted, obtain high sensitivity by coincidence counting and other background Rejection means are combined.

The hardware adaptations that realizes coincidence counting is 5,083,026 the disclosed e of patent being used to survey U.S. Patent number ⁺-γ (positron-gamma-rays: pg) in the detector of emissive source.10ns after meeting positron of emission and γ photon is in the time, and positron and negatron are buried in oblivion two of the generations γ photons with 511kev energy of propagation in opposite directions.A plurality of scintillation detectors are used for writing down these three and meet high energy (the γ photon of E 〉=250kev), the incident that lacks this triple gamma-rays features all is rejected.These instruments have a serious limitation, particularly aspect the big quality and high price of isotopic type that can be used and scintillator crystals.

According to patented claim WO 95/10308, it is 5 corresponding to the patent No., 532,122 United States Patent (USP), its disclosure combines as the reference data here, and is wherein a kind of that be used for trace and per hour have the gamma-rays of the ultralow background of the order of magnitude of a counting and the method that meets quantitative measurment of X ray emitting isotope is disclosed.

People's such as Oesterlin number is 4,005, people's such as 292 United States Patent (USP), Horrocks number is that 4,016,418 United States Patent (USP), the number of Coffey are 3,974, people's such as 088 United States Patent (USP) and Fymat number is that 4,682,604 United States Patent (USP) has all been discussed separately or counting gamma-rays that meets and X ray the time, yet they all are confined in the highly active application.

An object of the present invention is to provide a kind of detector of ultralow background, it is specially adapted to the weak gamma-rays/X ray emitting isotope (CGX isotope) that meets, and another purpose is to utilize the purpose that photon comes quantitative measurment CGX incident optionally as a kind of means and reaches background Rejection that meets that excites generation from the atomic nucleus of the isotopic feature of CGX and electron shell.

Further purpose of the present invention is by eliminating all stronger background sources background per hour to be reduced to degree less than an incident.Another object of the present invention is to overcome CGX count mode optionally to compare the defective with intrinsic low detection efficiency with single gamma radiation counter, provides the sensitivity and the detection that can detect inferior skin (sub-pico) Curie magnitude sample to be less than 5 * 10 ^-21Mol tracer molecule, zeptomole/ml (Zepto mole/milliliter), or even the single bimolecular ability of big spike, have greater than 10% detection efficiency and about 1% repeatability.

Another object of the present invention provides a kind of equipment, and it can be worked under non-meeting (single photon) pattern and can work down meeting γ-X ray emission (CGX incident) count mode, and at 9 orders of magnitude (10 ⁹) on have very big dynamic range and be better than 5% linearity.

Detector according to the present invention satisfies these purposes.They have the ability of polychrome (multicolor), and this is because several isotopes are can be in same sample measured and distinguished.They can be measured many different samples and produce the very high result of repeatability.They comprise self-scale and autodiagnosis.They can provide 100 microns or lower spatial resolution.All these advantages all can be achieved in the movably inexpensive equipment smaller and more exquisite than legacy equipment.Since according to the raising of instrument of the present invention sensitivity, isotopic concentration can reduce.Thereby reduced the cost that isotope obtains, reduced the irradiation of human body and alleviated the radioactive waste handling problem.

Multi-photon sniffer (MPD) that is used for surveying radioactive isotope in the sample (meeting γ/X ray (CGX) emissive source) comprises being used for surveying in the radiation detector that separates and (for example meets radiation from the CGX emissive source, gamma-rays and X ray) as the device of exporting pulse, be used for on-line analysis pulse shape and height so that discern the device of the pulse characteristics of single photo emissions, be used for screening and (for example giving up spurious pulse, non-gamma-rays that meets and X-radiation) device, be used for suppressing the isolated body that compound radiation shield chamber of the device of background radiation-preferably and absorbs X ray, be less than the device of the emissive source (for example CGX) of about 100 picocuries with the quantity that is used for containing in the quantitative measurment sample.

Further purpose of the present invention and advantage can obtain embodying from following detailed description with the accompanying drawing.

By reading the following detailed description with the accompanying drawing content that the present invention may be better understood, wherein:

Fig. 1 has shown the calcspar of photon detector.

Fig. 2 has shown the detector assembly part.

Fig. 3 is the calcspar of photomultiplier transit pedestal tube that comprises the one of amplifier and high-voltage power supply.Fig. 3 A to 3C has shown the example embodiment of each building block.Fig. 3 A has shown PMT (photomultiplier) pedestal, when Fig. 3 B has shown negative high voltage power source and Fig. 3 C amplifier and wave-shaping circuit.

Fig. 4 has shown the figure according to the dynamic range of MPD of the present invention.

Fig. 5 has shown the dynamic range of the MPD that compares with a chromatograph.

Fig. 6 has shown the schematic layout pattern that has the order sample MPD of sample change device about.

Fig. 7 is the calcspar according to MPD embodiment of the present invention.

Fig. 8 a, 8b and 8c are the process flow diagrams of method according to an embodiment of the invention.

A typical embodiment according to MPD device systems of the present invention is presented among Fig. 1.As illustrated, there are five major parts in this exemplary system, comprising:

1. two photon detectors, for example scintillator/optical sensor modules;

2. masked segment comprises an isolated body;

3. a sample supporting base is clipped between two photon detectors;

4. the detection electronic circuit comprises power circuit; With

5. comprise that data are obtained, the signal processing of pulse shape/highly analyze and show.Select and arrange all these parts of exemplary embodiment so that make radioactivity background minimum.

In explorer portion 20, two have suitable optical sensor 26, and for example the scintillation crystal 22 of PMT is placed on a common axis substantially Face to face.They are kept apart by a suitable isolated body 32, and spacer thickness is most preferably less than 8mm, and the bipyramid hole 34 that has central authorities is loaded on wherein facing to two crystal 22 radiation sample 36.The dimension of selecting hole 34 is so that its open solid angle is just in time surrounded the surface of crystal 22.Isolated body 32 preferably limits the phase mutual interference between the crystal 22, and selects its some this bottom event of thickness limits.Two detectors are placed among the composite shielding chamber 55 to reduce because the background that the surrounding environment radioactivity causes.This screened room can be from 0.5 kilogram to 20 kilograms according to its different application weight.Each optical sensor 26 also is equipped with radome 27.

At work, the energy that is deposited in the scintillation crystal 22 converts charge pulse to by optical sensor 26, converts potential pulse to then in the pedestal 30 of one.These pulses are shaped by low noise prime amplifier 52 fast, as the demonstration in detail of institute in Fig. 3 A-3C.The electronic circuit of pedestal also comprises the high-voltage power supply of supplying with optical sensor 26 and the amplifier 54 of high-gain.The shaping prime amplifier 52 of special " triangular shaped " is used to allow to meet soon the energy resolution of becoming reconciled.From the signal A and the B of two detectors 26, and meet trigger pip A+B, be imported among a digital storage oscilloscope based on PC (DSO) plug-in unit 58, it is used to carry out quick real-time pulse shape/pulse height analyze under software control.

Software the most handy Borland Turbo Pascal and C that the support that moves on PC is analyzed based on the pulse shape of DSO plug-in unit ⁺⁺Programming with Pascal Language helps making the procedure code high modularization like this.Transparence is standardized with being easy to.By some modification of software, identical equipment can be applicable to various application and not need hardware is changed.The assembly language programming of the most handy IBM PC of most important program of time makes the efficient maximization of obtaining with analytic signal like this.

DSO plug-in unit 58 has two input ends and an additional input end, and this additional input end is as obtaining triggering, and it has at least 8 analog-digital converter (ADC).It can monitor two input channels simultaneously on the sampling rate of 10MHz at least.Signal is with height to 100 * 10 ⁶The sampling rate of individual sampling/second is obtained and is stored in the machine carried memory continuously up to detecting a trigger pip, and in view of the above, back triggering (post-trigger) data point of a predetermined quantity is acquired.Stop in case obtaining, the content in the machine carried memory can be used by host CPU 59.

Any one of DSO passage can both can and/or trigger electronic circuit 56 and realize as triggering, triggering in other words by software.Quantity, the gain on passage and the trigger condition of sampling rate, trigger point, back all can be provided with by PC I/O port, and machine carried memory can directly be visited by the window of a 4k byte, for example, this window allows to instruct or DMA (direct memory visit) is transformed into other peripheral hardware and reads fast by the string that uses CPU.

The pulse shape analysis plays a part such, promptly will separate owing to the false pulse area of radiogenic pulse and other according to following feature.When a photon is absorbed by the combination of a scintillator/PMT or scintillator/photodiode, its produce one have character shape and with the proportional pulse of estimating amplitude of the energy of photon deposition in scintillator.On the contrary, the shape of the spurious pulse that the electromagnetic induction spectrum is sent out in reading electronic circuit can not define so well.Spurious pulse comprises the quick afterpulsing (rapid successions) of single narrow spike pulse, this pulse, electronics noise and PMT dark pulse at random.In the pulse height analyze system, spurious pulse can be polluted spectrum and the total signal that reduces system and the ratio of background that is obtained considerably.In addition, manyly also can distort by detecting " very " pulse that photon produces, when for example, (packing phenomenon) or the pulse that produces when photon cause distortion by the electromagnetism pickoff signals (pick-up) that meets when two discrete incidents occur in the time interval of a weak point.Such incident thickens the power spectrum of being obtained, and therefore according to shape analysis, or is rejected, or is correctly explained.High-frequency electronic in the front end electronic circuit is learned noise energy spectrogram, has reduced energy resolution.Yet by the pulse shape analysis, power spectrum can be improved to the degree of the true resolution of optical sensor.

To discuss below in order to reduce some considerations in the background design.Following background source is reduced in exemplary embodiments according to the present invention significantly:

The radioactive contamination of A1 scintillation crystal;

The radioactive contamination of A2 photomultiplier (PMT);

The radioactive contamination of A3 screened room;

A4 is from the energetic gamma rays of environment;

B1 is from the gamma-rays of being sent out by neutron spectra of scintillator, PMT and screened room;

B2 is from the gamma-rays of being sent out by cosmic ray spectrum of scintillator, PMT and screened room;

B3 is because the direct bump of cosmic rays;

The dark pulse of C1 PMT;

The PMT dark current that C2 is sent out by cosmic ray spectrum;

D1 electronics pickoff signals (pick-up);

D2 vibration pickup signal.

First group of background source (A1-A4) produces the background level of the several countings of per second (CPS) order of magnitude.The classic method that reduces this group background comprises the use of ultrapure material, and purity surpasses 99.999% usually.Yet purification process is very expensive to be difficult to be applied among the economical apparatus that is used for biomedical applications.The statistical method of deduction background is subjected to the restriction of statistical sample incident and can only be applied in the bigger situation of signal background ratio (S/B), for example S/B＞10.

The background that second group of background source (B1-B3) has a per minute 0.1-1 count level.Effectively screened room and ripe pulse shape analytical technology can be used for suppressing this background, but effectively the use of screened room trends towards very expensive.In addition, but effectively the use of screened room usually causes the geometric configuration of detector to become complicated and has limited the usage space of sample, thereby has reduced the purposes of equipment.

The 3rd group of background source (C1-C2) produces per hour several incidents (cph).These source electrodes are difficult only to be suppressed by hardware means.Meet, the synergistic combination of hardware means and ripe pulse shape analysis can suppress about 90% of this class background.Yet this need be based on the hard work of the line pulse shape analysis of digital storage oscilloscope (DSO).

The 4th group of background source (D1-D2), promptly electronics with the vibration pick-up noise, be to depend on very much system and present position.The typical noise in each unit that traditional electronic circuit based on NIM (Nuclear Instrument Module) presents is 0.1cpm, and it depends on the sum of the plug-in unit that uses.Even used the good concentric cable of ground connection, 10 to 20 cables are used for being connected with a typical NIM system, and observed electromagnetic noise is about 1cpm.In addition, the use of external high pressure power supply also influences the level of pick-up noise negatively.

To be less than the per hour level of a spurious counts in order reaching, should to use special low noise electronic circuit.Between the increase of the electronics pick-up noise that suppresses the online calculation requirement of the necessary system of background source B1-B1 and C1-C2 according to the present invention and cause, exist trade-off relation each other.

Isotopic selection is discussed now.Being most suited to EC emissive source that the present invention uses is listed among the form 1-4 that number is 5,532,122 United States Patent (USP).EC emissive source (emitter) typically has two to meet photon, and one of them is always because the X ray of the relative low energy that rearranges emission of atomic shell.In addition, some Augers (Auger) electronics can occur, it can advantageously be used for obtaining very high spatial resolution.For preferred radioactive source I ¹²⁵, its second photon also is low energy; Three peaks are arranged on its power spectrum, and energy is respectively 27,31 and 35kev.Design a MPD detector and be included in detection efficiency (DE), energy resolution (dE) and the compromise consideration between time response.Photon energy influences the selection of detector cells to a great extent.In the situation of high energy emissive source, wherein have at least the energy of a γ photon to surpass 100kev, the inorganic scintillator that density is bigger may be economical and practical, and for the isotopic detection of EC, a variety of detectors can use, and comprise scintillator detector, semiconductor detector and gas detector etc.

Best, the CGX emissive source is the isotope that can form the element of covalent bond, or the isotope of the element that can be sequestered in organic compound.Preferred isotope is I ¹²³, I ¹²⁵, I ¹²⁶, Br ⁷⁶Or Br ⁷⁷And isotope I preferably ¹²⁵

Half life period is 60 days EC isotope I ¹²⁵Be particularly preferred.According to former instrument result that obtain and that write down in chart of nuclides, the emission that meets of one of the atomic nucleus gamma-rays of 35kev and several possible X ray in the 27-31kev scope accounts for I ¹²⁵7% of decay sum.Yet, use the system that has improved of the present invention, experiment has disclosed the 25-35% that the actual coincidence number accounts for the decay sum.

The CGX emissive source is most the isotope in the group of the lanthanides isotope family.This family's element comprises 54 isotopes with identical chemical property, and they can be distinguished according to their different decay electron photon energies.Catch the chelating group of metallic ion by use, CGX group of the lanthanides family isotope can be introduced into as the spike to biomolecule.About chelating group being added the principles of chemistry that are incorporated in DNA subelement and their condensate is well-known.

To discuss below for being used for surveying I ¹²⁵The material of ultralow background CGX system select.Detection is from I ¹²⁵Gamma-rays require scintillator detector to have good energy resolution.In general, NaI (Tl) crystal/PMT is combined to obtain best energy resolution.Yet the use of NaI (Tl) causes extra hard X-ray background, and this is because feature iodine absorption edge causes.According to the present invention, by realizing preferred CaF ₂/ PMT combination can be eliminated this background effectively.

The all material that surpasses the 1mg quality that uses in the CGXD system is all screened out is used as radioimpurity radioactive impurity.Contain K ⁴⁰The most handy quartz of glass or special low background silicic acid pyroceram replace.Iron-bearing materials also is excluded owing to radiocobalt pollutes.Fortunately, the plastics of some type, for example teflon (teflon ^_) and polyacrylic, be acceptable, and ultrapure copper, tin and lead also are acceptables.

Diagnosis: diagnostic uses of the present invention comprises dna sequencing, dna fingerprinting and various forms of competition and/or binding analysis, for example radioimmunoassay (RIA).Use the I of pci (picocurie) level ¹²⁵Isotope is as input, and being exposed to the toxin and the germ that may rest in specimen or the reagent is more than employed micro-I ¹²⁵The problem of on safety, more being concerned about.

This system can be applied in and measure inferior vast mole (＞10 in the such diagnostic test of IA (immunoassay), immuno-PCR (PCR) and dna probe and IRMA (immunoradiometric assay) ^-18M) biomolecule of quantity.For the background level to 1CPS can obtain appropriate signal background ratio (S/B), the radioactive isotope of dangerous quantity is used in former IRMA technical requirement.Because lack the place of abandoning that allows, radioactive waste must leave the place (that is: hospital, university and factory) that produces discarded object in, produces potential radiation and biohazard.According to the present invention, can be abandoned by the solid test residue of biohazard regulation limit, this is because their activity ratio environmental exact details is also low.Liquid residue will comprise most of radioactivity, and will be lower but the residue that its activity ratio is given birth to from existing biomedical technology (for example radioimmunoassay (RIA)) has, and normally much lower than phreatic radioactive level.Therefore, may allow in many cases directly to abandon.

The advantage of " interlayer " detector geometry is discussed now.A unit according to equipment of the present invention is " interlayer " geometric configuration, and one of them sample is placed on two independently between the scintillator detector, and each is read by an independent PMT or suitable parts.The interlayer geometric configuration is counter, because it has caused two cover parts, comprises PMT, and this is main background source.And passive screened room is quite expensive, and the whole shape of detector assembly looks a bit clumsy, obviously, the user is seemed so unfriendly.At last, compare with well shape geometric configuration, the geometric configuration of interlayer has reduced detection efficiency.

Yet on behalf of the optimal compromise result between several below requirements: *, the use of the geometric configuration of interlayer can operate the ability that can work again under OR (non-meeting) pattern under AND (meeting) pattern; * allow the geometric configuration of asymmetric detector structure; * absorb minimizing and/or scale of the counterfeit part of making trouble (artifacts); With

At the main source based on the sample-out count in the gamma radiation counter of scintillator is this a part of radioactive contamination of detector itself.In order to reduce the actual radiation composition of background, can optimize the volume of scintillator.With I ¹²⁵Decay relevant low-energy and X ray stoped effectively and is being less than the thick Nal of 1mm (Tl) or is being less than the thick CaF of 1.5mm ₂(Eu) among the scintillator.Yet it is unpractical making a well shape detector with so thin thin slice, particularly considers the needs that PMT and scintillator are coupled.Generation be, preferentially select plane scintillator geometric configuration, some is low for detection efficiency that to the greatest extent let it be.In practice, diameter 2 " the detection efficiency of planar detector to place the little source (diameter is several millimeters) in the middle of the detector for one be about 40%.By using two identical planar rondure detectors, allow radioactive source between two detectors, the whole detection efficiency of system is improved, and relies on the degree reduction of geometric configuration.

Separating of detector also has other favourable aspect.It can distinguish the two-photon incident from the single photo-event with twice photon energy in half situation.It can also screen background by using anticoincidence inhibition technology.Yet each detector module has the PMT of a separation, because dark pulse and the counterfeit part of making trouble of diversified electronics of PMT, this has just increased inactive background composition.Therefore, it is desirable screening such on-radiation incident effectively by pulse shape analysis according to the present invention.

The detector geometry of interlayer has more performance than the geometric configuration of well detector or planar detector.Its in the qualitative property column of the scintillator detector of these three kinds of different geometric configuratioies in table 1.Table 1

Detector	Detection efficiency	Energy resolution	Background
Well detector	Fine (〉=50%)	Generally	Difference
Planar type detector	Difference (≤40%)	Good	Good
The sandwich type detector	Good (〉=50%)	Good	Fabulous

Repeatability and reliability are key characters concerning Biomedical Instruments.In many detectors, the source of typical error is self-absorption and because in detector/in the variation of the sample location of detector front.These errors can easily minimize when sample is liquid, and the use of well shape has very large benefit in this case.Unfortunately, to cause not be the problem of processing of footy sample in the use of liquid.Modem diagnostic methods is used such form usually, and wherein biological sample sticks on the solid surface or the product of a detachment process, and this product is attracted on the appropriate filters.For example, the electrophoresis product is captured or is forwarded on the film by gel.When use has the sample of big surface/volume, especially when biological sample is distributed in the inside on surface of the film that solid state filtrator, carrier or thickness can not ignore unevenly, perhaps when biological sample attached to the surface of these materials on the time, be good with the detector with flat shape.

When using two essentially identical planar detectors, each detector has and independently reads electronic circuit according to the present invention, can reduce the quantitative counterfeit part of making trouble widely.Can ignore with the position of sample when accurate when self-absorption, two detectors provide essentially identical counting rate.Yet even counting rate is different in two detectors, sandwich shape also allows the high efficiency application of asking poor/compensation scheme.

According to the present invention, use sandwich shape that some other advantages are arranged, particularly for effective background Rejection.Many bottom events are because the electromagnetism in PMT picks up pulse and dark pulse causes.By means of two fine detectors that separate, electromagnetism picks up pulse and can be detected by the pulse of comparing in two detectors greatly.Therefore, a pair ofly be separated from each other but have the detector of same electronic circuit under the anticoincidence pattern, to work so that suppress electronics and the pulse of picking up vibration.

In the single detector structure, because the K among the PMT ⁴⁰The background that pollution causes is the important component part of whole background.When using two planar detectors, being deposited on an energy in the detector has very big difference with the energy that is deposited in another detector usually, and this just makes and might suppress owing to pollute the background that the β emissive source of scintillator, PMT and screened room causes.The use of suitable isolated body makes the high-energy photon that might further eliminate owing to from device external penetrate the background that causes.It also is useful to suppressing cosmic rays.

Another significant advantage according to sandwich shape of the present invention is its versatility.The best realization of the present invention is to use two essentially identical detectors, is used for surveying isotope I ¹²⁵I ¹²⁵Situation some is special, that is, a plurality of photons are launched to meet mode, but their energy is very approaching, are respectively E=27,31 and 35kev.Therefore, for I ¹²⁵, can use two identical thin scintillators.Yet, the corresponding very big a plurality of photons of many other important source emitted energies, usually photon is grenz ray (E＜50kev) and another photon is the gamma-rays of nuclear, for example E＞100kev.For instance, for I ¹²³Situation, it has energy to be respectively three lines of 27kev, 31kev and 150kev.In this case, according to one embodiment of present invention, have the different scintillator of two crystal thicknesses sandwich detectors may be optimal selection.Further, the light-operated switch element can be used to survey the very big photon of capacity volume variance.

When using scintillator detector, it is suitable physically keeping apart scintillator as much as possible so that the X ray interference of sending out is composed in reduction each other.If the volume of sample less relatively (a few hectolambda), this can reach by the thick lead of 1-5mm or copper foil are inserted in the sample supporting mass.Keeping apart of detector effectively will be at single photon I ¹²⁵Energy range interested (ROI) in background force down twice.Separating for based on CaF of detector ₂(Eu) background of system has very different effect, and this is because these detectors can not be at I ¹²⁵Produce secondary X-ray among the ROI.CaF ₂(Eu) use helps constituting the MPD detector that is used for bulk sample according to of the present invention.Shown quite high sensitivity based on the detector of NaI (Tl) or CsI (Tl) for the shape and the diameter of perforate in the isolated body.

((binary dilutions) finishes according to equipment of the present invention and the relatively dual dilution by using commercially available radioiodinated TSH antibody between Memorial Sloaw Kettering Cancer center (MSKCC) and other local detector.The molecular wt of this antibody is about 40,000 dalton.These tests of great majority are finished by using a cover scale sample.Other scale NaI ¹²⁵And I ¹²⁵The dilution dope of-dCTP carries out.For radioactive standard, bromination 3,8-diamido-5-ethyl-6-phenylphenanthridineand carries out the specific activity that iodine labeling becomes about 0.1mCi/ml with 125.Subsequently, dilute with the factor sequence of isopropyl alcohol with four times.This cover calibration source comprise ten samples, coverage from several thousand dpm to about 0.1 dpm.Each dilution one hectolambda volume is placed among Eppendorf (Ai Pengduofu) bottle of being made by thin plastics of 200 microlitres.

These results relatively prove that MPD is than the better radioactivity of other gamma ray detector measured intensity.The detection efficiency and the energy resolution of two different MPD detectors are also contrasted.Meet in the pattern non-, the MPD equipment of different embodiment according to the subject invention is compared the radioactivity background that comparable detection efficiency is arranged and approximately hang down 50 times with traditional equipment.In addition, traditional system in about ± 5% error range by scale and our MPD system in about ± 1% error range by scale.

Table 2 has shown some most important parameters, promptly for one group of commercial gamma radiation counter and two according to of the present invention based on NaI (Tl) and CaF ₂(Eu) MPD detector has been listed detection efficiency and background respectively.Table 2 has also shown the MPD equipment of working under AND (meeting) pattern, when using by meeting between two photons of EC emissive source emission, its background compares further with the background of working under OR (non-meeting) pattern and is lowered, the sensitivity that has caused like this being improved greatly.Yet, can see that its detection efficiency has also reduced some under the pattern meeting.Table 2

Detector	Detector efficiency	For I 125Background (cpm)
γ-counter (1)	70％	200
γ-counter (2)	80％	150
γ-counter (3)	50％	60
γ-counter (4)	50％	60
MPD1[NaI(Tl)](5)	60％(10％)	2(0．1cpd)
MPD2[CaF 2(Eu)](6)	50％(5％)	1．5(0．3cph)

(1) Beckman 5500, are positioned at American Red Cross, Gaithersburg, Md.; (2) Bedeman 5500 gamma counters are positioned at Lehigh university, Bethelheim, Pa.; (3) gamma ray spectrometer LKB 1272, are positioned at Georgetown university, Washington D.C.; (4) gamma ray spectrometer LKB 1292, are positioned at MSKCC, New York, NY; (5) " the MPD equipment of NaI (Tl) scintillator based on two 2; (6) based on two 2 " CaF ₂(Eu) the MPD equipment of scintillator.

For the MPD detector, be given in the performance (value in the bracket is the numerical value under the AND pattern) under two kinds of count modes of OR and AND.

The optimization of permission according to the present invention in the MPD system of OR and the work of AND pattern will be discussed now.Sandwich detectors allows to work meeting under (AND) pattern, thereby background is reduced several magnitude significantly.Yet, also relatively low (for I for its detection efficiency of this obtaining mode ¹²⁵Radioactive source and diameter are that the detector of the sandwich shape of 2 " to 3 " is 5 to 15%), this will prolong gate time widely for the low emission source.Yet, also can work in non-meeting under the pattern according to sandwich detectors of the present invention.This non-pattern that meets is called the OR pattern.Under this OR pattern, the incident of count recording in any detector.Therefore, total system is similar to the detector of well detector or any non-segmentation as a detector job on the one hand at this.In the OR pattern, detection efficiency is higher (for I ¹²⁵Radioactive source and diameter are 2 " the detector of sandwich shape, its representative value is 50%), but lost by the additional benefit that meets the background Rejection preferably that obtains.

MPD according to the present invention with the work of OR pattern reduces by using following mode to obtain sizable background: optimize scintillator thickness; The branching ratio of correct interpretation two-photon incident (is 50% to the double detector system), it can reduce to counting region interested on the single photon peak; Anticoincidence; With the pulse shape analysis.

At diameter is 2 " CaF ₂(Eu) among the MPD of crystal, the background under the OR pattern be 1.5 to 2cpm and detection efficiency be 50%.During the OR pattern is obtained, the identified and counting of coincident event, the AND mode counting therefore needn't try again.In case that obtains finishes, MPD output OR and AND enumeration data.If the activity of radioactive source is (approximately 5pci, or the I of vast mole on the activity of OR background equivalence ¹²⁵Tracer element), the OR data should be used.Because the higher detection efficiency of OR counting, these data have lower statistical error.If the OR incident approaches half end of OR pattern, AND mode counting data are used, and this is because its much lower background.

As about estimation, for greater than 10dpm, promptly approximately the radioactive source of 5pci is worked under the OR pattern better.Yet, can both use well at 1-20dpm scope OR and two kinds of patterns of AND for radioactivity.About the sensitivity of this scope, software is used to OR and AND data are combined so that obtain the best estimate of true counting rate.Like this with regard to energy minimization because the counterfeit part of making trouble that statistical error (AND data) and high background (OR data) cause.Below 1dpm, the AND pattern provides goodish signal background ratio for activity.

According to one of important software function of the present invention is suitably to estimate the dead time and the accumulation of counting rate are revised.Obtain based on the pulse of DSO and to comprise and must compensate in the relatively large dead time, especially for the situation of high count rate the dead time.In MPD equipment according to the present invention, this is by using an additional counter/timer plug-in unit to finish.

This counter/timer preferably has at least two impulse meters and a timer.A counter should be counted the whole hardware trigger that produced by signal Processing (Conditioning)/triggering plug-in unit, and another should only be counted and meet triggering.Timer should write down the time of irradiation with very high degree of accuracy.In the preferred embodiment, should use model PCL-720, it is provided by JDR micro equipment company.This plug-in unit has 3 counters, and one of them can be transformed into a timer by interconnector.These counters have 16, so they can be with at least sense data of per second to prevent losing of data.The 3rd counter come timing by line, and it carries out timing by one second 1/2,500 interval in this embodiment.

When the counting beginning, MPD software command DSO plug-in unit obtains first pulse and while count initialized device and timer.When the PC hardware timer interrupts arriving each time (for example, each 55 milliseconds), the numerical value in counter and the timer is read out and is added among total counting/elapsed time.When counting is finished, (tale is divided by the time of reading from timer for counting rate in the corresponding counts device, if DSO triggers with meeting trigger pip, use meets flip-flop number, otherwise uses the counter of tale) be used to adjust the counting rate of all incidents, not repressed incident and the incident in all area-of-interests (ROM) according to following formula:

Cpm _IAdj=Cpm _i* (Cpm _{Total Counters}/ Cpm _{Total DSO}) Cpm here _IAdjBe the counting rate (per minute is a unit) among i the ROI that dead time loss has been done to adjust, Cpm _iBe the original DSO Cpm among i the ROI, Cpm _{Total Counters}Be the total cpm in counter, and Cpm _{Total DSO}It is the gross-count rate before the inhibition in DSO.

This adjustment can be done whole compensation to the dead time loss, and makes the linearity of counting only be subjected to the restriction that pulse is piled up when high count rate effectively.Can for example be less than OR and AND counting rate data from the scale program in 3% the scope and match.

The performance characteristic of CGX detector is discussed now.Compare with traditional equipment, detector according to the present invention has fundamentally improved performance.It improves part and comprises sensitivity, repeatability and dynamic range.

Sensitivity: the direct indicator of the sensitivity of radiation counter (limit of Tan Ceing in other words) is its suitable activity (BEA) of background, promptly produces the activity of the radioactive source of the counting rate that equals background in detector.This performance factor is to be determined by the background of counter and detection efficiency two aspects.

For MPD detector according to the present invention, the typical BEA under OR pattern (non-meet detection) is the scope in 3 to 4 decays of per minute, and this activity is equivalent to when being less than 2pci I ¹²⁵Activity.This be according under the OR pattern for about 50% detection efficiency (DE) with at I ¹²⁵The energy region of interest in be to draw under 1.5 to 2cpm the background counting rate condition.Therefore, the sample of a 5pci will have about 3 S/B value.

For MPD detector according to the present invention, the typical BEA under AND pattern (meeting detection) is the scope in 1 decay every day, is equivalent to several femtocuries (femto Curie, 10 ^-15Curie).This is according to about 7% DE (detection efficiency) under the AND pattern with at I ¹²⁵Region of interest in per fortnight be to draw under the background counting rate condition of 1 counting.

For a radioactive source (10pci) that activity is more weak, commercial detector can't the quantitative measurment sample or is only provided the S/B value near 1 criticality measurement result.Yet, the I of a 10pci ¹²⁵Sample uses CGX detector according to the present invention to carry out duplicate measurements, has carried out 400 times measurement in the time interval in several weeks.Measured activity and known I ¹²⁵Half life period be compatible.These measurement results are to obtain under the OR mode of operation, wherein do not use to meet pattern.

In the pattern that performance strengthens, promptly according to meeting pattern and stricter pulse shape analysis, though DE somewhat low (5-10% is to 50%), background has reduced several magnitude.For the pattern of this enhancing, performance depends on the size of sample.For diameter is that the standard model test tube bundle of 12mm is said, DE be 6.5% and background be 0.25cph, produced the BEA of 4dph.For less sample (diameter is 4mm or littler), DE is that 5-7% and background are 0.5-1 counting jede Woche, and it is equivalent to the BEA of 3dpd (decays of every day).Therefore, in the improved pattern of this sensitivity, might detect activity is about 10dpd, promptly comprises and is less than 1,000 I ¹²⁵The I of atom ¹²⁵Radioactive source.

Repeatable: the fabulous repeatability of using MPD equipment according to the present invention to measure reaches by selecting electronic component, and these electronic components have very low temperature coefficient, scintillator [CaF ₂(Eu)] part of temperature-responsive compensation, because the inhibition of the dark pulse that cosmic rays causes and the inhibition of electromagnetic interference (EMI).

Known that all these effects all are time correlations.For example, from the temperature dependency of the signal of scintillator in traditional commercial gamma ray detector, cause on 3.5% level the daytime/night effect.The every day of cosmic-ray flux and annual fluctuation cause the effect of a few percent in well detector under low counting rate.At last, the sensitive sensitivity of electromagnetic interference (EMI) is caused when 10cpm activity is following significant daytime/changes night.The inhibition of these effects/compensating pole the earth has improved the repeatability of measuring and has eliminated all diurnal effects in MPD.

Mainly determine according to the measurement reproducibility of MPD equipment of the present invention by the repeatability of sample placement location in counting statistics, clock accuracy and the instrument.MPD equipment according to the present invention is all quite stable in very big a period of time.Variation and the detection efficiency of not observing background are stable.In order to test the measurement stability of MPD equipment in several weeks, measured about 1,200 time of identical sample (50 receive Ci) was being removed sample and then be placed on the position from supporting base before each the measurement.For each measurement, sample is counted up to collecting 10,000 incidents (be equivalent to ± % statistical error).

Another advantage according to MPD of the present invention is the possibility that has reliable scale.Owing to used " interlayer " shape that can reduce absorption and the counterfeit part of making trouble of sample placement location and used the I that can carry out scale with Eldridge scale program ¹²⁵, it is possible improving scale.For example, same MPD equipment is with the 50 radioactive source scales 25 times of receiving Ci.Average DE is defined as 49.1%, and its standard deviation is ± 1.7%.Compare with commercial detector, the error range of the common scale of typical commercial detector to ± 5%, but in fact for activity at 0.1 radioactive source of receiving below the Ci, its scale uncertainty is approaching ± 10%.

Dynamic range: for all analyses and biomedical application, the linearity of crossing over many orders of magnitude is the features that expect to have.Often be, the level of primeval life compound should can compare with the level of metabolin, and the level of metabolin may much lower the order of magnitude.Most of existing traditional instruments have very limited dynamic range.

Photoemulsion only allows quantitative measurment in the scope of 1.5log (logarithm).Typically, the response of detector is subjected to the restriction of low counting rate and high count rate.Therefore, replace desired linear response, the characteristic detector effect is the curve of a S shape.When hanging down counting rate, well shape detector is subjected to the serious restriction of intrinsic background.Similarly, optical detector, for example chromatograph is subjected to the serious restriction of photon background.On high level of activity, accumulation or optical interference distort the linearity of Conventional detectors.In fact, gamma ray detector is for high count rate, and up to about 1,000,000CPS is near desirable.Therefore, typical well shape counter in the dynamic range of about 4 log, promptly from about 100CPS to 1,000,00CPS has shown linear response.

The background Rejection technology of in MPD equipment according to the present invention, using in the OR pattern from 1cpm to 1,000,000cpm promptly surpasses in the dynamic range of 6 log and allows reliable quantitative measurment.When having used the AND mode of operation of having improved, be 1cpd for this pattern background, MPD detector according to the present invention has the linearity of the dynamic range that surpasses 9 log.Higher counting rate (surpass 500,000dpm) on, may cause saturated by the pulse pile-up of scintillator.Although response no longer is linear in this scope, the dead time of MPD can't enlarge, and therefore counting can be counted and the result be proofreaied and correct accumulation.Under low counting rate, the linearity of response is subjected to the restriction of background.The result who measures with MPD is presented among Fig. 4.I ¹²⁵The dilution of the reagent of spike has shown the perfect linearity that is low to moderate the tested activity of 0.1Zeptomole/ sample levels above 5 orders of magnitude.

Linearity and commercial chromaticity detector according to the response of MPD of the present invention compare, and the advantage of MPD is tangible.The dynamic range of MPD detector is more much bigger than chromatograph.In order to carry out this research, streptavidin-HRP (horseradish peroxidase) is by iodine labeling, and same sample is measured with the commercial chromatograph that is used for the ELISA test with MPD.Measurement result is presented among Fig. 5.The chromatographic sensitivity of the remolding sensitivity of MPD at least the dynamic range of two orders of magnitude and MPD than well about five orders of magnitude of the dynamic range of chromatograph.In the scope of chromatograph reliable operation, use MPD according to the present invention to obtain identical result with using chromatograph.

CaF is discussed now ₂(Eu) use of scintillator.The natural selection seemingly of NaI for the MPD instrument (Tl) scintillation crystal.In meeting pattern, square being inversely proportional to of background Rejection and energy resolution, the energy resolution of NaI (Tl) is than other scintillator good about 50%.In addition, have the scintillator NaI (Tl) of suitable energy resolution, CsI (Tl) and CaF ₂(Eu) in, sodium iodide scintillator is the fastest.According to standard practices, background Rejection is proportional to time-resolved square.Reckoner is shown in based on background ratio among the MPD of NaI (Tl) and uses the background of other scintillator should hang down about four times, and for very little, for example＜10 the such MPD system of the radioactive source of microlitre reaches the background of 0.5 counting of about jede Woche (0.5cpw).

Yet comprise based on the shortcoming of the equipment of NaI (Tl): * NaI (Tl) is fragility on mechanical property, for example, and when it being placed with the local time of thermograde and/or in transportation, it often breaks; * NaI (Tl) must seal and fully when sample is placed near its position, and for example when operation spatially separately during MPD equipment, the thin Al paper tinsel or the Be paper tinsel that cover the scintillator front surface are easy to tear; * when using big sample, because the cross interference of the X ray between the crystal, its background degenerates significantly in based on the MPD system of NaI (Tl).

(comprise CaF with other scintillator ₂(Eu)) replacing NaI (Tl) causes very little background to increase.Yet, read electronic circuit and data processing software by optimization, for the I of small sample ¹²⁵Or I ¹²³, based on CaF ₂(Eu) MPD system compares the background that reaches much at one with system based on NaI (Tl).For large sample, based on CaF ₂(Eu) its background will be got well about 10 times in the MPD system.

Since several not reasons intuitively, CaF ₂(Eu) for I ¹²⁵Detection has aforesaid astonishing low background.At first, for MPD according to the present invention system, in the AND pattern, the main source of background is the detection of the grenz ray that emission and some energy source with detecting in another crystal of absorbing are consistent in a crystal.When using NaI (Tl), any absorption that has the outside photon of E＞35kev in crystal all causes launching 26kev or 32kev photon again, and 26kev or 32kev photon source are in the rearrangement of atomic shell.Therefore, when using NaI (Tl) crystal, launch feature iodine X ray.These rays can not with I ¹²³Or I ¹²⁵The 25kev of daughter nucleus emission and the Te X ray of 31kev distinguish.In fact, for CsI (Tl), this effect even bigger is because the characteristic X-ray of Cs and I is almost identical with the X ray that radioiodine is launched.Fortunately, CaF on the other hand ₂(Eu) only comprised the lower element of atomic number.Therefore, their characteristic X-ray has the energy that is less than 15kev and can distinguish with the X ray of radioiodine.Therefore, NaI (Tl) or CsI (Eu) preferably are applied to atomic number and are less than 40 or greater than 70 EC radioactive isotope, for the EC radioactive isotope of atomic number between 40 to 70, preferably use CaF ₂(Eu) scintillator.

CaF ₂(Eu) second advantage even more exquisite and more not directly perceived.CaF ₂(Eu) be very slow scintillator, its characteristic light is approximately 5 microseconds die-away time, promptly than slow about 25 times of NaI (Tl).Traditional detector uses fast as far as possible detector, has the background of about 1cps.When background was forced into several cpm, the main source of background was because cosmic rays and cause from the dark-current pulse of PMT.The glitch that causes owing to the energy by the cosmic rays deposition in crystal itself can obtain the solution of part by the gross energy of analyzing deposition.Particularly for the X ray of low energy, for example for I ¹²⁵, this method can curb more than 95% of cosmic rays that penetrated scintillator.This method comprises the secondary that is suppressed at effectively in the cosmic-ray shower.

Yet under the situation of MSD system, crystal itself is extremely thin, and the surface of PMT negative electrode is about 50 times of plane of crystal.Impinge upon the snowslide that high energy cosmic rays on one of PMT anode causes electronics, these electronics are exaggerated successively.Such pulse has caused the surface energy deposition more much lower than the energy of cosmic rays, promptly has sizable overlapping between the energy of being composed the dark-current pulse of sending out by cosmic rays in PMT and the energy from radioiodine.This background source causes per minute n counting is arranged in each PMT in the detector that uses scintillator-PMT combination, or in meeting pattern per hour several countings.Yet the energy that is deposited in the scintillator typically causes composing the longer pulse of sending out of pulse than cosmic rays in PMT, and it has the characteristic time constant of about 0.2ns.

In practice, inhibition ability is subjected to the restriction of several detector features.These eigenwerts comprise the performance of parameter line pulse shape analyzing system of characteristic response time, the shaping amplifier of scintillator.For example, in the MPD system, in the requirement of low price be applied between the performance of the online digital storage oscilloscope (DSO) of pulse shape in analyzing and have trade-off relation (trade-off).Have only and only about half ofly in PMT, compose the pulse sent out by cosmic rays and can be suppressed by a pulse of among NaI (Tl), composing.In PMT, composing the pulse sent out by cosmic rays and at CaF ₂(Eu) difference of the pulse rise time between the pulse that produces in is very big, promptly is respectively 0.1ns and several μ s.Based on CaF ₂(Eu) in the MPD system, surpass 95% the counterfeit part of in PMT, compose by cosmic rays of making trouble and curbed by online.

The observation that about 40 NaI (Tl) crystal is reached 2 years finds that variation has taken place NaI (Tl) crystal property, and some of them (about 10%) are broken owing to thermal stress and other (about 15%) flavescence owing to their hydroscopicity.On the contrary, to 20 CaF ₂(Eu) crystal reaches the observation in 1 year and does not find that crystal property has obvious variation.

Generally speaking, the CaF of sandwich shape ₂(Eu) scintillator can be obtained superior background Rejection effect, particularly when the major diameter of radioiodine sample can be measured.CaF ₂(Eu) superior mechanical property provides another advantage that surpasses NaI (Tl).

The selection of scintillator and their dimension will be described now.Traditional scintillator is optimized to and makes detection efficiency is maximum.Therefore, selected typical thickness is approximately to be twice in stopping power on interested energy.In addition, for typical sample size, for example its diameter is 0.5 inch, and the diameter of selected crystal is 3 inches or even 4 inches.Yet background is proportional to the crystal volume haply in the nonlinear function of the complexity of scintillator dimension.For example, for 3 " crystal, traditional design be they and 3 " PMT be coupled.Yet the PMT of 3 " PMT than 2 " has much bigger radioactivity, and this radioactivity derives from the naturally occurring isotope in PMT glass.Therefore, the bigger surface area of glass wall and bigger thickness have caused obviously higher radioactivity background in bigger PMT.Therefore, opposite with traditional hypothesis, in order to optimize the performance of low background MPD equipment, preferably selecting diameter in the present invention is 2 " detector and obviously thin crystal.

MPD detector according to the present invention have can self-scale advantage, self-scale is by using I ¹²⁵The source is carried out two-photon and is met to survey and finish.Yet in order to finish this function, a pair of detector should mate finely mutually, promptly similar characteristic should be arranged.For the ease of selecting the good a pair of detector of coupling, all crystals in given MPD system preferably cuts down from the same bigger crystal of diameter.These crystal are installed in the copper pipe of low-activity background.X ray window/reflecting surface is made up of MgO and the thick Al paper tinsel of 50 μ m.Or, also can use thin teflon (Teflon) paper tinsel.Optical window is made by the quartz that 2mm is thick at least.

Diameter and thickness optimization:,, find that best scintillator size is that diameter is 2 " according to the present invention for monocyte sample MPD equipment.For the standard sandwich shape, promptly be separated from each other about 1/2 when a sample is placed on " two detectors between the time, be the highest corresponding to the S/B of this size.Yet, quite smooth as the optimal curve of the function of crystalline size, for example, (S/B) [3 "] ≈ 1.2.When for I ¹²⁵When optimizing the MPD detector, for CaF ₂(Eu) optimum thickness of scintillator is 1.5mm; Crystal thickness changes to 3.0mm from 1.0mm and only causes that (S/B) changes about 50%.

Choice criteria: preferably every crystal is carried out optical check, give up crystal crannied or that transparency is not intact.Then, the PMT that crystal is installed in the low-activity background through selecting goes up and carries out a series of Acceptance Tests.First test is energy resolution and a detection efficiency of checking whole crystal.Unfortunately, PMT is far from evenly, should measure the performance of the not same district of PMT.In order to accomplish this point, the surface of scintillator/PMT combination shields with the cumulative lead ring of diameter, radioactive source be placed on lead ring in the heart.First lead shield is covered with the hole of a 0.5cm.Check energy resolution then in the center of scintillator/PMT.Two other lead shield covers also are used to check energy resolution, and wherein one is the lead rings that one inch lead ring and another piece are two inches.For I ¹²⁵The CaF that only has dE/E (FWHM)≤21% ₂(Eu) crystal just is accepted.In addition, their radioactivity background preferably≤0.5dpm.In general, 2 to 3 crystal are rejected and return producer in per 10 a collection of crystal.

The selection of low background PMT and the optically transparent material between PMT and scintillation crystal is described now.Carefully PMT is selected very much according to MPD equipment requirements of the present invention.If extra price can be tolerated, preferably select the quartzy PMT of customization.Popular integral type scintillator/PMT combination and commercially available PMT pedestal also can use, but will do suitable modification according to the present invention.The radioactivity background greatly owing in these integrated components, used stainless steel to cause, and commercially available PMT pedestal has quite high radioactivity.PMT pedestal according to the present invention has a composite shielding chamber between pedestal and PMT to be used for reducing the radioactivity background.In addition, the optical coupled thing (quartz) by a suitable low-activity background is coupled PMT and scintillator optically.

In order to be reduced in the radioactivity background in the MPD system, the scintillation crystal of 2 " and 3 " is selected best PMT.Following PMT parameter is important; Radioactivity background, detection efficiency, energy resolution, in the lip-deep homogeneity of photocathode, dark current, long-time stability and signal correlativity to temperature and magnetic field.

Testing procedure and result: the candidate's photomultiplier tube from five different manufacturers is tested, and the PMT that Electron tubes company (ETI) and Hamamatsu company produce has optimal results.To this tests aspect two at electronics property and radioactive contamination from about 40 PMT of these two manufacturers.The PMT of Hamamatsu company provides better electronics performance to a certain extent.They all have the features such as energy resolution that superior detection efficiency is become reconciled.In addition, their dark current is also low slightly.Yet for the pipe of 2 " and 3 ", best single pipe is from ETI.These pipes have big slightly electronics performance profile in a collection of pipe.Consider the radioactivity background, preferably select the pipe of ETI, for example, low 10 times of the pipe of the background ratio Hamamatsu that it is surveyed.

PMT stands a series of test to determine whether they satisfy choice criteria.First test is to check energy resolution and detection efficiency on the crystal of a surface exposure.Next step, the different piece of PMT is checked its energy resolution, this is by using three different plumbous late holes to finish, and radioactive sample is placed among the plumbous door screen, and first shielding is covered with the aperture of a 0.5cm and the outer lead ring that second radome is an inch.The electronics parameter depends on employed isotopic energy to a great extent.For example at about 30kev (I ¹²⁵The source) energy resolution on at about 88kev (Gab ⁷The source) between differentiating, the result on finds not have association.

Relative radioactivity background in PMT is 2 by PMT being placed near a diameter ", thickness is the CaF of 2mm ₂(Eu) measure this CaF on the position of detector ₂(Eu) " PMT's low background 2 of a detector and a selection is coupled.Whole test system shields well with lead, tin and copper.At CaF ₂(Eu) background in the detector 20 to the energy range of 40kev (I just ¹²⁵The energy region of interest) in measured, the background of measured result during with the PMT that is not studied compares.The pulse shape analysis is used for screening real event part and the counterfeit part of making trouble of electronics.In test process, under the situation of not testing PMT, find CaF ₂(Eu) background in the detector is 0.7cpm.The counting rate that the PMT of ETI increases usually is also not obvious, and the bigger additional background of the general generation of the PMT of Hamamatsu.

The radioactivity background of finding in the PMT of Hamamatsu is shockingly big, and average background is 3.5cpm, but can observe the background up to 4.2cpm.Therefore, the model of preferably selecting ETI to produce be 9266KB 2 " PMT is with it and a NaI (Tl) or CaF ₂(Eu) scintillator coupling.Average dE/E (FWHM)=17.4%, minimum and ceiling capacity resolution is respectively 16.2% and 20.7%.Average detection efficiency is 37.4%, and minimum and maximum probe efficient is respectively 31.1% and 40.3%.Because the radioactivity background that the PMT of EMI causes is quite low, average background is 0.2cpm, and minimum and maximum background is respectively 0.1cmp and 0.55cpm.About 20% PMT finds to have the background that is higher than 0.3cpm.After these PMT were given up, average background was 0.13cpm, and minimum and maximum background is respectively 0.11cpm and 0.28cpm.Another kind of preferred model is the R-2486 type PMT that ETI produces.

Encapsulation: traditional PMT typically is encapsulated in the prefabricated aluminium or stainless-steel tube.These commercial PMT that install that go up have increased the radioactivity background, therefore, are preferably in to install and do some modifications.Should do crack or flaw inspection to PMT.Clean PMT with isopropyl alcohol and remove any particle or pollutant.Next step, the whole glass surface except the window district covers with the black electrical adhesive tape of four floor.After these work are finished, with black electrical adhesive tape helically individual layer covering all adhesive tapes except that close article one adhesive tape in window district.Subsequently, cover whole PMT, comprise plastic base with two-layer Copper Foil band with electric conductivity sticker.Another layer black electrical adhesive tape helically covers on the copper surface.Next, connect the whole packaging process of finishing after the spiral helicine black belt of one deck with one deck Copper Foil band again.

There is the silicon gloss oil to be coupled between crystal and the PMT.Must carefully operate in order to avoid between crystal and PMT, introduce air bubble.Next step, with white teflon band on the PMT of crystal and PMT joint.Crystal is fixed with 4 to 8 extremely thin aluminium foils that have viscosity.The copper strips of one deck viscosity is fixed together to guarantee PMT and crystal around crystal and PMT, and it also plays the effect that stops outside X ray.3 inches PMT is fixed together both with the aluminium strip of viscosity.At last, in order to ensure the leakage that prevents visible light, cover on the copper with one deck black electrical adhesive tape helically.

For low background counting, should shield the radioactivity that prevents from the photomultiplier tube that is coupled with scintillator to scintillator.Can not shield detector and prevent from the energetic gamma rays of PMT and do not reduce the optical characteristics of scintillator/PMT system.Yet, might shield scintillator by the transparency window of use such as quartz between PMT and scintillator and prevent β particle and lower energy photon incident.This window 24 is presented in the exemplary embodiments of Fig. 1, and it has optics oil reservoir 23.Select to have simultaneously superior optical characteristics and highly purified quartz.Quartz and CaF ₂(Eu) optical density (OD) is mated fairly goodly, also is acceptable concerning NaI (Tl).Preferably select the thick quartz window of 5mm.In quartz, there is not observable radioimpurity radioactive impurity.

Scintillator can reach by using than quartzy material with higher stopping power gamma-rays and the better shielding of X ray.In order to reach this purpose, preferably select highly purified GeO ₂With germanic glass, because they have low-down intrinsic radioactivity background.Their high atomic number and density are also superior than quartz window.The window of this several millimeters thick can stop lower energy photon effectively, and the β particle, and the optical characteristics of scintillator/PMT system is degenerated.The optical characteristics of germanium dioxide (gelica) and germanite glass and NaI (Tl) coupling is than good optical properties quartzy and NaI (Tl) coupling.

Another kind of alternative plan is to use leaded highly dense glass, especially resembles lead fluoride (PbF ₂) and the such highly dense transparent crystal of bismuth germanium oxide (BGO).Under the situation of using BGO, should use non-doped crystal so that can not produce because the counterfeit part of making trouble that the impurity among the BGO causes.The optical density ratio CaF of these materials ₂(Eu) or the optical density (OD) height of NaI (Tl).Therefore, preferably use the special optics oil of skim, for example in silicone oil, add PbF ₂Powder is so that be complementary the optical characteristics of optical characteristics, window and the PMT of scintillator and window.Selectively, can use by germanium dioxide (gelica)/highly dense window/germanium dioxide (gelica) three layer interlayer windows, the thickness of germanium dioxide (gelica) should be more much smaller than the thickness of high-density optical window.

Screened room/isolated body; Require to stop the radiation of environment according to the exterior shield of MPD of the present invention, as at the screened room 55 shown in the exemplary embodiments of Fig. 1." thick Pb screened room is enough for the MPD detector made from the thick scintillator crystals of about 1-1.5mm, 2.Increase screened room thickness can not further reduce the background on the earth surface significantly, and possible main cause is owing to remaining background is mainly caused by cosmic rays.Yet, if screened room only forms by lead since the screened room itself that radioactive particle causes excite the secondary lead X-ray of appearance in background source.Therefore, preferably use multilayer screen, put the thick tin of one deck 1-5mm in Pb screened room inside and be used for absorbing lead X-ray, put the thick copper of one deck 1-5mm in tin layer inside and be used for absorbing the tin X ray.The X ray energy of copper itself is quite low (8-9kev), and it is at I ¹²⁵Area-of-interest outside.NaI (Tl) and CaF ₂(Eu) scintillator all has enough energy resolutions, can lead and gives up to fall these pulses to be better than 90% n.Commercial Cu paper tinsel has enough purity and does not bring extra radioactivity background into.The exterior shield chamber should surround detector assembly on all faces, comprise PMT and pedestal.

Sample supporting base/cross interference cancellation element is also made by the thick copper coin of 1-5mm, stereotype or copper/plumbous composite plate.This thickness is to stoping the iodine X ray enough.

Should under the condition of radioactive source the material that is used for screened room be tested not having, method be used for selecting for the low-activity background and be placed on CaF in the selecteed low background screened room ₂(Eu) detector measurement background.Each time of testing with 2 hours, measured result produces statistical error approximately ± 10%.There is the radioactivity background all will remeasure 4 hours, if new value still on 0.9cpm, is just given up this screened room greater than each screened room of 0.9cpm.In general, must give up 20% screened room.

The one PMT base assembly that is used for high stable MPD equipment is described now.The accurate counting of low-activity radioactive source requires the detector system of high stable.Observed drift causes mainly due to the variation of environment temperature, and the variation of environment temperature causes the drift of the gain that the drift of yield of scintillator and PMT and electronic circuit are read.In order to make PMT keep stable electronic circuit and the high-voltage power supply of preferably having selected to improve.

The high-voltage power supply (HVPS) that is used for PMT should following method be stablized, and negative feedback, the use of promptly introducing high-gain have low-temperature coefficient (1-2ppm/ ℃) fiducial chip (1% metalfilmresistor that for example, MaX580) has low-temperature coefficient with use.The voltage divider that is used for PMT is to make according to the resistance of same type.Make each grade Amplifier Gain all be less than 5 by operational amplifier and the diversity gain that uses high stable, thereby the temperature dependency of prime amplifier is minimized.

Drifting problem long and that temperature causes can be compensated by adjusting Amplifier Gain in PMT and scintillator, so that the power spectrum of obtaining is remained unchanged.Electronic circuit allows their gain of control of digitizing ground.When being connected with the temperature readout equipment that is arranged in detector system, this electronic circuit allows to regulate continuously gain the drift that temperature causes is compensated.Can under non-meeting (OR) pattern, obtain effectively for the scale of each detector temperature, and can use among the obtaining of OR and two kinds of patterns of AND by a series of measurement to gain.Whole scale process can be robotization and periodically finish to compensate long drift.

PMT pedestal: for the low background detector of making biomedical applications, because HVPS and the dependence of voltage divider (VD), the performance/danger of high-tension cable, the radioactivity background of various elements and the electromagnetism pick-up noise between PMT and the prime amplifier, commercial HVPS and PMT pedestal are unsafty.Therefore, preferably select the PMT pedestal of one, put/the shaping amplifier block before comprising HVPS/VD/.

Traditional PMT pedestal seldom uses the design of one.Classical way is, only voltage divider is placed among the PMT pedestal.This way causes sizable electronics pick-up noise, and this pick-up noise is undesirable in MPD.The equipment of several commercializations has the feature of PMT pedestal band one voltage divider and prime amplifier.Maximum integrated for the PMT pedestal, preferably include HVPS, voltage divider and prime amplifier, because the use of high-tension cable can become problems such as loop and electromagnetism pick up with causing and may have the danger that electrocutes, when particularly in the environment of high humility, using portable set.

The radioactivity background of PMT pedestal is 2 by PMT being placed near diameter ", thickness is the CaF of 2mm ₂(Eu) measure this CaF on the position of detector ₂(Eu) " PMT is coupled for detector and a selected low background 2.Total system shields well with lead, tin and copper.Then, CaF ₂(Eu) background in the detector is 20 to the energy range (I of 40kev ¹²⁵Region of interest) on measure, and the background during with the PMT pedestal that is not studied compares.Screen real event part and the counterfeit part of making trouble of electronics by finishing the pulse shape analysis.From CaF ₂(Eu) measure on the base position of the surperficial 2mm of crystal and 5cm because the background that the PMT pedestal causes.What measure on first position is background and represent that second locational measurement it to what extent influences the performance of MPD (length of the PMT of use is about 5cm).Under the situation of the PMT pedestal that is not used in test, find CaF ₂(Eu) background in the detector is 0.7cpm.

When being positioned on the position of scintillator 5cm, because the background that the PMT base assembly causes does not influence the background of whole M PD.Yet in the time of on being positioned near the position of scintillator, its background is but shockingly big.Therefore, several PMT pedestals will be taken apart, the radioactivity background of each part are tested separately, that is: * plastic H V connector; * potentiometer chain resistance and electric capacity; * Pb/Sn/Cu composite shielding chamber; The housing * HVPS module and the prime amplifier module of * plumbous supporting base and PMT pedestal.

It is shocking that we find that maximum radioactivity background is the high-tension connector of doing from plastics, cause mainly due to the β particle.This background can attenuate very effectively by a thin plastics protective ring.After revising through this, the radioactivity background of PMT pedestal only account for PMT the radioactivity background less than 10%.

(quantitative measurment for example≤0.1pci) may need to reach the Measuring Time of several hours to the low concentration radioactive source, and therefore, any slow drift of electronic circuit can both influence the measurement of these long-time (1 hours).The main root of this drift is PMT.Amplitude gain causes the signal drift of temperature correlation to the strong dependency from the high pressure of HVPS.

High-voltage power supply: voltage divider is applied to negative voltage the dynode (pin one-11) of PMT and is applied on the negative electrode C by a RC circuit from HVPS.Foregoing circuit in PMT base assembly 30 is presented among Fig. 3 A, 3B and the 3C.The voltage divider resistance of being represented by R7 and R8 has low temperature coefficient (≤100%ppm/ ℃), therefore makes the output signal of PMT keep stable.The HVPS 50 of negative polarity preferably includes voltage stabilizing DC that Matsusada company produces to DC converter, voltage regulator 66, a feedback circuit and a comparator circuit amplifier 70 that contains accurate benchmark 68 (temperature coefficient is about 3ppm/ ℃).Owing to reduce the importance of HVPS output, preferably select to have the element of low-temperature coefficient to temperature dependence.

Performance that the foregoing circuit structure reached is than using commercial NIM plug-in unit, for example from Ortec, ten times of the obtained performances of the plug-in unit that companies such as Canberra or Tennelec buy, and reduced widely MPD round the clock between instability.

A preferred HVPS has following quality: input voltage :-15--18VDC input current; ≤ 120mA output voltage range: 300-1,100V[DC] noise :≤50mV peak is to peak temperature stability: ≈ 20mV/ ℃, under normal output voltage (1,000V)

Another critical elements in the PMT pedestal be in the optimization shown in Fig. 3 and the 3C prime amplifier/wave-shaping circuit 52.When using the pulse shape analysis to suppress such as because during background that the dark-current pulse among the PMT causes, leg-of-mutton pulse shape is best.On the contrary, most of business machines use Gauss pulse to be shaped, and it makes energy resolution the best of low energy X ray and preferably selects Gauss pulse to be shaped when use is only carried out pulse height analyze such as multi-channel analysis.Amplifier/wave-shaping circuit preferably includes based on the prime amplifier 52 of EL2030 low-noise current feedback amplifier with based on the output amplifier 54 of the OP64 type amplifier with high increment and great dynamic range.Output amplifier 54 does not need to proofread and correct and harmonize in the course of the work.Just as shown in FIG. 3, pulse differential chain C ₁, R ₁With integration chain C ₂, R ₂Determined the parameter of output pulse: rise time t _T400ns[800ns] at the pulse width t=3ms[4ms at 0.1FWHM place]

First group of numeral is corresponding to use NaI (Tl) scintillator, and the numerical value in bracket is corresponding to CaF ₂(Eu) scintillator.Resistance chain R ₄, R ₅Determined the gain of amplifier 54.Gain is selected between the scope 20-50 and by potentiometer to be adjusted.This numerical value depends on the characteristic of given PMT and scintillator crystals and the output amplitude of about 2V is provided for the photon of 30kev.

Last PMT pedestal/components for operational amplifier according to the present invention has following characteristic: noise≤50mV peak is to peak gain 20-50 dynamic range 50,000 compensation≤2mV input signal t _T=200ns, t=100ms, [negative pulse] output signal t _T=400ns, t=3ms, [positive pulse] spiking output 10V is non-linear≤and 2%, power supply DC electric current≤20mA on whole dynamic range, voltage: from ± 12VDC up to ± 18VDCPMT base size diameter: 2.2 ", " weight 1Lb (pound) (the inside Pb/Cu radome that comprises 0.5Lb) highly: 3.75

These electronic circuits have very high temperature stability and do not need during operation to be adjusted.These equipment are also produced easily and are debugged.When comparing with the NIM plug-in unit, they have high 10 times stability and production prices are quite cheap.

Highly sensitive and the low background of noise and temperature stability: MPD requires to promote the technical requirement of electronic circuit.Cause that spectral sensitivity and S/B can be divided into two classes than the condition that reduces: the long term drift (drift of gain, high pressure and temperature) of short-term noise (electronics noise and dark pulse) and electronics parameter.

For preferred detector according to the present invention, be about 16% and for NaI (Tl) for CaF at the energy resolution dE/E at 30kev place (FWHM) ₂(Eu) be about 35%.If electronic circuit is less than 10% to the influence that energy resolution degenerates, this will cause jamtosignal (N/S)≤0.016.Amplifier, high-voltage power supply (HVPS) and electro-magnetic shielding cover allow to reach jamtosignal (N/S)≤0.005.Main electronics noise source is filtered out by electronic circuit, and the shape analysis of remaining noise by online software suppresses.

When using commercial HVPS, temperature dependency is to I ¹²⁵Cause measurable pulse height drift.Use is during according to preferred HVPS of the present invention, and gain has the temperature dependency of environment temperature can measure following degree of accuracy.In order to reduce the HVPS influence of temperature variation, the voltage divider that is used for PMT can be realized by the resistance that use has a metallic ceramics 1% of low-temperature coefficient.Further, the use in current feedback and super steady baseline voltage source allows to have the small-sized HVPS (asking for an interview Fig. 3) of following parameter: the dc voltage input :-12--18V output :-300--1,100VDC electric current input≤120mA output:＜1mA output noise≤100mV impulsive noise≤150mV peak is to the peak, and frequency is 100kHz

For example, impulsive noise is than using with the good 2-3 of impulsive noise times with HVPS.

The HVPS of commercialization and HVPS according to the present invention are compared at the temperature dependency of 25 ℃ of HVPS output voltages between to 70, baseline/noise ratio was presented in time interval of 24 hours (to be turned off in winter under the condition of heating installation and measures, that is, making the temperature variation in daytime/evening is about 15 ℃) have and be better than 1% baseline stability.Compare according to the performance of negative polarity HVPS of the present invention and the performance of HVPS PS 1800 series (production of Electron Tubes company), under identical initial temperature (25 ℃), open this two kinds of HVPS, be heated to 60 ℃ then simultaneously, commercial HVPS has shown the voltage drift of a few percent, but is not aware of because the variation that heating causes according to the output proof of HVPS of the present invention.

The MPD of monocyte sample: describe a kind of preferred examples now.Detection efficiency is optimized in current gamma radiation counter design usually.According to the present invention, purpose is background is minimized and to keep detection efficiency reasonably high.In order to reach this purpose, be necessary to eliminate the radioactivity background source, use best counter shape (shape that comprises screened room and isolated body), carefully alternative pack, use stable electronic circuit and use the online software that background signal suppresses that is used for.

Therefore, MPD comprises following subsystem: photon detector for example has the scintillator detector that PMT reads; Isolated body/screened room subsystem; Read electronic circuit; Obtain with data/analyzing subsystem.

If described, preferably select CaF for good stopping power and reasonable energy resolution ₂(Eu) scintillator.Such system obtains uncommon background Rejection, has improved the ability of quantitative measurment trace target isotope.This equipment can be worked under foregoing two kinds of patterns, can obtain high DE (to I ¹²⁵Being＞5%) the radioactivity background reaches 1 counting of per minute (1cpm) under OR (non-meeting) pattern.Meeting under (AND) pattern, though to I ¹²⁵Its DE is below 20%, but can obtain the ultralow radioactivity background of 1 counting every day (1cpd).These results go up with relatively little screened room (being approximately the lead of 20kg) to obtain at the earth's surface.This system is round by commercially available parts and proven technique cheaply and design.

Describe now surveying I ¹²⁵Preferred embodiment for the MPD detector of the best.The calcspar of MPD detector is presented at Fig. 1 stereographic map that neutralizes and is presented among Fig. 2, and it comprises that geometry, the multi-photon of " interlayer " meet and the pulse shape analyzing subsystem.Detector 20 comprises that isolated body is made by heavy metal by isolated body 30 separated two modules of low-activity background, and typically isolated body is the interlayer of being made by the Cu/Sn/Pb that counts millimeters thick.An aperture 34 of placing sample 36 usefulness is arranged in isolated body 32.

Two detector modules 20 lump together in the compound passive screened room 55 that is sealed in heavy metal, and screened room is made by the pure material of radioactivity, as previously mentioned, are typically become with copper by plumbous, tin.The material of maximum atomic number, for example plumbous, it is thick to be placed on outermost layer and at least 1 inch.Then be the material of lower medium atomic number, tin for example, it is a n millimeters thick, for example 1-2mm is last, uses several millimeters (typically being 2mm) thick very pure copper layers.

Each detector module comprises following element: * inorganic scintillator crystal 22, and its thickness will help given emissive source (emitter) most; * highly purified optical window 24 is placed between scintillator and the PMT; * through PMT 26 that select, the low-activity background; * go forward one by one (graded) passive shield 46 between PMT 26 and PMT base assembly 30; * the PMT base assembly (as shown in Figure 3) that comprises high-voltage power supply 50, voltage divider 51 and prime amplifier 52.

As scintillator, be less than the thick CaF of 3mm ₂(Eu) crystal is best.Optical window 24 is thick ultrapure quartz of 4mm at least, and through optical polish and use optical coupled agent 23, i.e. the silicone oil of low-activity background.

Hang down K through the PMT 26 that selects by containing ⁴⁰The glass of impurity is made, and preferably selects preferred 2, and " PMT makes the background of generation be less than 0.1cps.Preferably PMT pedestal 30 is separated with PMT 26 by the go forward one by one method of shield 46 of use, the barricade 46 that goes forward one by one is to be made by the metal that three layers of atomic parameter differ greatly, and the typically this barricade that goes forward one by one comprises thick tin and about 0.1 " the thick Cu of about 0.2 " thick lead, about 0.15 ".

The PMT pedestal 30 the most handy materials with low-activity background through selection are made, and for example, do bearing support with fine copper or aluminium.Used resistance and electric capacity are selected the model of low-activity background for use, and the scolder that uses the no In that is made by pure tin or tin/lead metal.All of PMT pedestal 30 are passive all selects the model with low-down temperature drift for use with active component.Also use the active compensation technology of the gain drift of eliminating temperature correlation among the present invention.

Two kinds of patterns of OR and AND all are used for data to be obtained and analyzes, and a multiple tracks DSO 52 is used for online background Rejection.Triangle is shaped and the software of fast pulse suppresses also to obtain using, and this fast pulse is because the signal that cosmic rays is composed in PMT 26 causes.Preferably select the pulse rise time of about 0.75 μ s and the slow pulse fall time of about 5-10 μ s.

Self diagnosis and self-correcting technology are used to be adjusted at reliably the counting rate in OR and the AND pattern, more particularly, are that online baseline recovers and pile up effect inhibition technology.In meeting pattern, shape and time that key is to use DSO 58 to mate from the pulse of two detector modules meet.In being better than 100ns the estimation requirement that meets of pulse and be shaped for triangle, the long duration pulse can suppress from being the relation of trading off between the requirement of the dark current of PMT.Yet, overcome these conflicting requirements based on the line pulse fit procedure of software.

Pulse shape is analyzed: the data in paired scintillator system are obtained to depend on to amplify and be shaped and are used for subsequently analysis from the signal of the PMT of each detector and the power spectrum of setting up a combination.Then, suitable isotope to desired is interested can the district in to the counting integration to determine counting rate.Is 2 for one by diameter " NaI (Tl) or CaF ₂(Eu) sandwich detectors of scintillator composition, detection efficiency typically is about 50% altogether when the incident in the energy region of interest of only counting at single photon (ROI).For I ¹²⁵, it is about 70% that counting its detection efficiency of incident between 30 to 60kev is increased to, but the integral energy scope is doubled and therefore background is doubled.

The actual activity (per minute decays, or dpm) that counting rate (cpm or cpm) is converted to sample need be known counter detection efficiency (DE).For I ¹²⁵, DE can determine by using known Eldridge formula from the power spectrum of itself.Its DE will determine respectively for each detector, helps improving scale and degree of accuracy like this and comes the integrality (integrity) of test macro and the position of correcting sample by two estimated values of the actual activity of scale sample relatively.The power spectrum of coincident event can be used to improve calculating and the diagnostic purpose of DE.

The principal ingredient of on-radiation background is because the dark pulse in PMT causes in low-energy/X-ray detector.At I ¹²⁵ROI in, these dark pulses normally produce several cpm for two PMT systems.Yet the shape of these pulses is different with the shape that scintillator in detector produces, and therefore feasible examination based on pulse shape becomes possibility.The pulse shape of each incident or a plurality of pulse shape are by using a DSP plug-in unit 58 based on the dual input jack of PC and obtain and carrying out the fast pulse shape analysis.So just can give up PMT dark pulse and other electromagnetism with the vibration the counterfeit part of making trouble.Based on after the giving up of pulse shape, the background of system almost is smooth and stable significantly in the energy range of 15-100kev, and irrelevant with near the activity detector.

Detector: preferably selecting diameter is 2 " planar detector (NaI that 1mm is thick (Tl) or the thick CaF of 1.5mm ₂(Eu)).Less scintillator has reduced the DE of system and has reduced for its signal/background ratio of bigger crystal.Scintillator is that quartz window and the diameter of 3-5mm is 2 by thickness " the PMT coupling of high energy resolution, PMT selects the type of low background for use.The electronic circuit PMT signal that is built in the PMT pedestal 30 by use is read out, amplifies and is shaped.In order to reduce the flux of the background photon from the pedestal to the scintillator, with the plate that thick lead of 5mm and the thick copper of 1mm are made pedestal and PMT are separated, there are a plurality of holes to be used for the pin of PMT on the thin plate.

Screened room and supporting base: detector assembly is placed in the screened room of the lead+tin+copper that goes forward one by one (2 " lead, 1mm tin, 1mm copper).Detector is being placed Face to face, keeps 0.5 inch distance each other, and a sample supporting base/cross interference is eliminated plate and is placed between two detectors, and it is a copper sheet that 1mm is thick, is installed on the plumbous support.On copper sheet, leave opening and be used for placing sample.The shape of opening is decided by the style of use sample.A delrin guidance device that has the copper overcoat guarantees that all samples all can be in the detector system center.When sample style and sample supporting base change, system can enough Eldridge formula recalibrate automatically.

Data are obtained hardware; Data are obtained hardware and preferably are installed in the special-purpose PC and are used for controlling MPD.With reference to figure 7, the electronic circuit that data are obtained in an exemplary embodiment comprises trigger circuit 56, is used for the amplification module of each detector, digital clock/counter 57 and a two-channel 2-4 0MHz digital storage oscillograph (DSO) 58, DSO 58 promptly as 2 input MCAs again as pulse-shape analyzer.

Trigger circuit 56 produce a rectangle trigger pulse when surpassing the pulse preset the amplitude threshold and be recorded in any detector 26 for one.If when in two detectors, recording pulse simultaneously, produce a more trigger pulse of high-amplitude.Therefore might separately count coincident event and non-coincident event.Trigger pulse is sent to the external trigger input end of DSO.Trigger circuit can be combined plug-ins as described below.

The amplification module is adjusted the amplitude of pulse so that the interested window particle interior and identical energy that can distinguish the 0-1V that drops on DSO produces same magnitude in two passages pulse.

First of timer/counter 57 is as accurate acquisition time timer (reference pulse to 2.5kHz is counted).Second all trigger pulse that timer/counter 57 countings are produced by trigger circuit, and the 3rd the only numeration triggering relevant with coincident event.The data of obtaining from these counters are used for directly calculating because losing of causing in the dead time of the system that obtains and therefore make system can correctly count the radioactive source of high activity.

DSO 58 (the preferably commercial CSLite PC additional plug-ins of making by Gage company) can be enough 8 accuracy and up to the sampling frequency of 20MHz simultaneously to two input channels samplings, DSO 58 also has an additional external trigger input port.Data storage is among the neutralization of airborne (on-board) storer can be sent to host PC RAM by standard memory to storer by the PC data bus.Dead time be strictly p-n and can proofread and correct losing of causing of dead time by aforesaid rolling counters forward rate.Each incident be acquired with processed after DSO 58 equipped again and initialization.

The pulse peak shape is sent to the host PC 59 and with software from DSO 58 its amplitude and shape are analyzed.

At first, DSO 58 being arranged to be presented at continuously two input voltages in the passage also waits at the trigger pulse that triggers input end.When a trigger pulse was recorded, the back triggering that allows DSO 58 write down a predetermined number was counted and is stopped then.Peak shape (on 20MHz sampling the time have usually before 20 triggerings count and 108 triggerings after count) relevant portion be sent in the storer of host PC 59 and be used for analyzing.For example, transmitting each peak shape for one 486 DX66 computing machine takes time and is less than 200 μ s.

Signal adjustment/processing plug-in unit (SCPC) 56: can handle signal from two detectors in order to make MPD detector software.Trigger circuit are used for: 1) produce a trigger pip when any PMT produces a pulse; 2) be adjusted at two analog gains in the passage; And 3) be adjusted at time-delay between signal and the trigger pulse.

This hardware (asking for an interview Fig. 7) is preferably realized as the signal adjustment/processing plug-in unit (SCPC) 56 that is placed in the computing machine.SCPC plug-in unit 56 is characterised in that to have adjustable gain and each passage is all had triggering level and produces a TTL trigger pulse.The SCPC plug-in unit can directly receive as the signal of importing from PMT pedestal 30.The input end that signal through adjusting and trigger pulse directly are sent to DSO plug-in unit 58.

Binary channels SCPC 56 is designed to: the generation that the * simulation triggers starts DSO 58 in the pattern that meets pattern and input signal is sued for peace.* the generation of TTL triggering, enabling counting device 57 in two kinds of patterns.If * arbitrary input signal has the amplitude greater than a certain fixing level, forbid triggering.* the analogue delay of input signal.* the adjustment of DSO incoming signal level.* SCPC 56 has following parameter: * input signal (positive pulse): amplitude: 0.1-8V; Pulsewidth: 0.1-100ms.* low level adjustment: 0.2-5V is adjustable continuously.* high level adjustment: 0.2-5V is adjustable continuously.* output attenuatoin scope :-3--60db.* digital delay scope: 0.1-10ms.* analogue delay duration: (1 ± 0.01) ms.* output signal (positive pulse)

Simulating signal: amplitude: 0.1-1V; Pulsewidth: 0.1-10ms.

Transistor-Transistor Logic level: amplitude 〉=4.5V;

Pulsewidth 4-5ms.Simulation triggers: for " OR " pattern, amplitude 0.5V

For " AND " pattern, amplitude 1V pulse 4-5ms.* temperature stability threshold value＜0.05%/℃ coefficient of deviation＜0.01/ ℃.

Being combined in Fig. 8 a now is described the method according to this invention to the exemplary flow chart shown in the 8c.To can seeing significantly the description of this exemplary methods, this method can realize that these are all within category of the present invention having under the various processing environments of various software platforms from following.

Line pulse is given up software and is given up such pulse, i.e. the shape of these pulses is inconsistent with the pulse that is produced by the particle that stops in scintillation detector.The major part that is suppressed background is because noise, electromagnetic interference (EMI) and vibration noise among the PMT cause.

For a given detector, the shape of the pulse that is produced by radioactive events does not change along with the time, and does not rely on the amplitude of pulse within the range of linearity of amplifying yet.Therefore, a kind of method of giving up about pulse shape is that the pulse of being write down is normalized into a pulse with common amplitude, and using for example then, χ-square (Chi-square) check compares shape and " standard " shape of the pulse of process normalizing.Yet this work comprises a large amount of floating-point operations, finish these effectively and calculate the time that needs cost huge in little processing of common low price.

The another kind of method that can replace is just can finish the pulse shape house and get by determining many parameters relevant with pulse shape, and these parameters mainly or fully just can be calculated by the integer arithmetic computing.

Data processing: at the DSO that is provided for obtaining with after waiting for the initial step of a triggering, analytic system begins to calculate baseline and from the pulse height (step S3 is to S14) of each detector.Can know that from these steps incident is to occur among the detector A, still occur among the detector B, perhaps occurs among two detectors.The pulse amplitude is handled by current baseline,, just given up this incident if unacceptable distortion has taken place the latter.Numerical value in the tolerance interval of being set up by software when then, many pulse shape parameter are calculated and are provided with system compares.For example, these calculating are included in the pulse width (Fig. 8 b and 8c) at 1/4,1/2 and 3/4 place of pulse peak height.These parameters can comprise:

Pulse height;

Rise time;

Fall time;

Total pulse widths;

The shape of the rising part of pulse;

The shape of the sloping portion of pulse;

From the delay between the pulse of two detectors;

The pulse multiplicity;

Prepulse peak shape (pre-pulse trace); With

The comparison of using the least square law technology that arteries and veins is carried out shape and standard high-energy photon pulse shape.

The quick program based on integer calculations that is used for these calculating is moved very effectively on Intel processor.For coincident event (Fig. 8 b), finish an extra rise time coupling (alignment) and check.In pulse shape, pulse height with meet/after anticoincidence analyzed, an incident that is not rejected was added to (the 2D power spectrum of the power spectrum of the power spectrum of detector A, detector B or coincident event) among the suitable power spectrum.

Require 128 points for each pulse for each input channel DSO 58, have 8 resolution characteristic.The whole width of time window drape forming pulse (5 μ s) and before pulse is risen the scope of about 1 μ s.The digital processing of pulse starts from the calculating (step S4) to the mean value of 8 points in foremost, and this mean value has provided current baseline.If the baseline that is calculated is different from 0 value significantly, this incident is regarded as being rejected (step S5 to S7) by the distortion that pile up effect causes.Ensuing 120 points of peak shape are scanned (using the quick LODS instruction of 80X86 processor) maximizing.Overflow if detect, this incident is rejected (step S5 to S7).Otherwise amplitude is calculated (step S8 to S10) as the difference between peak value and the current basic line.This program is also stored the time bias value at peak.Then, begin to scan fast forward and backward from peak position, (according to LODS) to determine the time bias value of the point of crossing of this amplitude on some horizontal line, for example the point of crossing (step S15 to S20 and S26 to S28) on 1/4,1/2 and 3/4 horizontal line of amplitude.These data are enough to finish pulse shape and give up.

Incident processed intact after, DSO 58 the obtaining that be reset for use in next incident.Any incident that produces during handling has all been lost (dead time).When composing data processing, the counting rate that is calculated will be lost these and revise.

Obtain to be preset in given time interval and collect data, perhaps in the ROI of a selection till data aggregation to definite count value.Obtain also and can at any time stop by the user.

The scale routine: automatically equipment scale/ROI is provided with that routine is following carries out.The user can require software to carry out this step at any time.Do not need the sample crossed by scale, but require a high relatively activity (best 50,000 to 200, I 000dpm) ¹²⁵Sample.After a such radioactive source was put into detector, program was obtained 100,000 incidents, and all pulse heights and pulse shape was given up all work.Finish in case obtain, spectrum is analyzed to determine the region of interest (ROI) for single-photon (27-35kev) peak.Determine the counting rate (cpm) in this ROI.If the actual activity (dpm) of known sample, detection efficiency can be calculated from the ratio of cpm/dpm.In order to estimate the saturation activity of scale sample, program begins second now takes turns data and obtains, and pulse shape is given up inoperative (because the activity of scale sample is higher, need not to suppress background and do not have the real event part to be rejected) in this is taken turns.The spectrum of two detectors (A and B) is added up up to getting access to 200,000 incidents.

Subsequently, the spectrum of each detector is carried out the counting rate (meet spectrum also be used to help separately these peaks) of analytical estimating in a photon peak and two photon peaks.Then, the Eldridge formula is used to estimate the detection efficiency of detector and the decay rate of scale sample.By relatively checking from the estimated value of detector A and detector B whether data are consistent, and the mean value of these two decay rate is accepted as absolute activity, estimates detection efficiency from this absolute activity.For 2 " system, DE is usually in the scope of 50-60%.Have only a photon peak to be used as counting, under the situation of the sandwich detectors with electronics squelch, this method of counting only reduces detection efficiency about 15% and reduces about 2 to 3 times of background.

After scale/ROI setting was finished automatically, system was ready to come sample is counted according to the identical geometric condition of sample with the last scale that uses.Both obtained and can carry out in a time of presetting, also count enable is till make tale in ROI reach a numerical value that presets (this numerical value is determined the statistical error of counting).The actual decay rate of the DE estimation sample that calculates before then, program is used.The sample enumeration data generally is stored in the dish in the mode of ASCII character data file then, and these data files can be sent in database or the spreadsheet program so that analyze.

Software is that parameter is obtained/given up in the detector system setting of the new assembling of every suit, and it is also given up parameter and set up the internal data file and store these parameters for system determines best triggering level and pulse shape.In general these parameters might not redefine in the whole serviceable life of system, unless critical piece (for example, a PMT/ pedestal or DSO plug-in unit) is replaced.

Data mode: system program can be by user's preset count more than one sample or according to the same sample of desired number of times repeat count.If a batch sample is counted, program reminds the user to change sample after measuring each time, stores with identical ascii text file with all data.File comprises one and has the leader that date mark and system are provided with, and by the additional description of the sample of user's input, and for example, the user is with the input of GUI editor when the counting beginning.

Program can also be equipped with a simple data file browser, and file browser allows to watch and analyzes from single sample and the data that become batch sample.The user can select a data file to watch by menu system, watches the counting error of each sample, make counting and decay rate to the curve of sample number with print the data that have statistical error.Use for example commercial spreadsheet program to finish and analyze more widely and carry out data and merge.

The most handy Borland Pascal of software and assembly language coding are so that acceleration pulse processing speed and the seemingly GUI shell operation of window of use under the DOS environment.The another kind of selection is that software can use the Delphi software development system (BorlandIntemational) of nearest announcement under the MS-Windows environment, the Borlard Pascal language that this system's use is expanded.Those person skilled in the art persons can use other programming language, and this still belongs to scope of the present invention.

From scale and self diagnosis: MPD equipment according to the present invention comprises from scale and self diagnosis, they are realized by using the redundance in the spectrum information feature for the EC source, promptly use the single photon in the simple detector spectrum and the 2D spectrum (energy in detector A is to the scatter diagram of the energy in detector B) of two-photon peak and coincident event.Extra benefit comes from the MPD of the step-by-step counting subsystem that uses two separation, and these two subsystems are DSO 58 and impulse meter 57, and they allow to monitor the counting rate difference between two detector subsystems and allow to detect possible hardware fault.MPD software uses from the data of known isotope radioactive source acquisition and checks detector, PMT, HVPS and the working condition of reading electronic circuit.May polluting by measuring and analyze background spectrum of MPD surveyed.For a given EC isotope, by using this isotopic scale sample, software meets two kinds of patterns and automatically calculates detection efficiency to meet with non-.Any drift of each threshold value of diagnostic routine tracking gain and equipment is also calculated any desired correction.

After debugging, MPD has superior long-time stability; At I ¹²⁵The peak in short time (being less than a week) drift be less than 1%.1,200 independent measurement finishing with MPD shows, and is repeatable more far better than the statistical error of these measurements.For at 0.1-1, the radioactive source MPD equipment of 000pci1 scope allows to be better than 1% measuring accuracy.Its drift of operation that surpasses six months is less than 3%.

For the measurement on the Zeptomole level, MPD is operation all night often, and making round the clock, change degree becomes important.For the performance of scintillator/PMT combination, 5 ℃ temperature variation causes significantly, the approximately drift of 1-2%.In order to compensate this effect, can measure the temperature of crystal and come the corrected impulse amplitude by software.

Asymmetric detector geometry is discussed now.The example of handy single sample discloses an interlayer MPD structure of symmetry fully.This geometric configuration is suitable for the isotopic symmetry decay of CGX; On two transmit directions that meet between the photon, do not have interrelated.For I ¹²⁵, the energy of two photons is near identical, and identical energy makes and uses symmetrical detector to reach best performance.Therefore, the use for any other geometric configuration of symmetry decay is a poor efficiency.Yet, some other application is arranged, these are used proof and use asymmetric geometry can reach best performance index.Application according to this aspect of the invention, the asymmetry that all kinds can be used comprises following favourable variation, but being not limited to two detectors of these variations: * is made from a variety of materials, for example, two kinds of dissimilar scintillators be can use, a scintillator and a semiconductor detector perhaps can be used; * two detectors are different sizes, and typically, one very little big so that increase detection efficiency so that reduce background and one; * two detectors are as different functions, and one is that the spatial discrimination detector is non-spatial discrimination detector with another, and the latter is as trigger equipment.Typically, the spatial resolution detector is partly covered by the coding hole of suitable pattern, and second detector is exposed in face of the radioactive source fully.

Best structure is that these key elements are combined.In according to one embodiment of present invention, detector comprises NaI (Tl) crystal that a PMT with spatial discrimination is coupled.Yet, trigger detector and be a CaF who is coupled with dissimilar PMT from another producer ₂(Eu) scintillator.

MPD (abbreviating SR-MPD here as) for a spatial discrimination, system performance depends on the optimization of all parts of system, for example the geometric configuration of the type of the hole cover of the thickness of the thickness of the diameter of the type of scintillator, scintillator, scintillator, optical window and coding.

The MPD of high-resolution a, spatial discrimination is described now.When using by CGX isotope (I especially ¹²⁵) during the single sample of spike, the MPD of monocyte sample can produce sizable background Rejection.Yet, in many application, the spatial resolution that people need get well, for example, when measuring in detachment process (running gel, point smear (dot blots), chromatography on thin layer and the paper) and the radiolabeled distribution that in the dissection of tissue specimen is studied, obtains.

Very general 2D radioactive tracer distributes and comprises the product that is separated by electrophoresis, thin-layer chromatography (TLC) or high performance liquid chromatography (HPLC), and subsequently, separated product filters through suitable medium.These can be referred to as chromatogram.They are self-supporting normally, and promptly separated product is deposited on the surface that is attached to a mechanically hard thin plate in other words.Most popular that class that the 2D radioactive tracer distributes is the electrophoretic separation product that is adsorbed in the gel.In general, can be cured or their mechanical property of drying and other treatment raising gel.Yet, in this situation and many other situations in, more practical method be biomedical specimen holder between two block of material films.At last, the product of electrophoretic separation usually is transferred to and smears in other words on elastic membrane, and film i.e. also plastics of nitrocotton (nitrocellulose).These products are called as and smear target.

Use for all these, the MPD detector can be used to replace classical autoradiography and phosphorus imager.In all these were used, biomedical sample was the object of a 2D basically, and its thickness is less than the dimension of other both direction widely.Usually, sample is supported on its face by a suitable film.In great majority were used, thin stilt can be by low atomic number, and for example the material of plastics is made.Use this thin mechanical jack its objective is and allow it absorb less relatively X ray, for example be less than 5%.

The requirement of three competitions is arranged for the physical appearance of radiolabeled 2D diffusion target: 1) sample should be flat a being easy to mechanical treatment; 2) sample should be sealed the pollution of the detector that causes with the discharging of eliminating by direct contact or floating dust.3) X ray in the material absorbs and be reduced to bottom line around.

These three requirements are technical feature, the especially sensitivity that obtains unprecedented SR-MPD detector, and institute is prerequisite.At first, sample should be done flatly as much as possible, because the variable in distance from the sample to the detector surface causes the counterfeit part of making trouble in tested activity.In general, traditional detector carries out scale in ± 5% error range, and MPD reaches ± and 1% scale and repeatability.In addition, when sample is not flat, there is the loss of sizable spatial resolution.The unprecedented sensitivity of MPD means, even minimum pollution also is fatal to the integrity of measuring.Usually, not only biomaterial but also propping material all will be polluted.This situation can occur for smearing thing, be to use a kind of special buffering liquid to finish, be sent to the reverse side of film with the sub-fraction of radiolabeled electrophoresis product by diffusion owing to smear (blot).Similarly, the reverse side of TLC plate is usually polluted slightly.At last, when measuring with the sample of inferior picocurie, any extra absorption all can become a problem.Therefore, preferably select extremely thin thin layer that low atomic number material makes as package means.

Three kinds of radiolabeled methods that smear target of preferred encapsulation 2D are described below.For the sample of self-supporting, chromatograph (chromatographic) plate or smear target for example, easy and the most practicable method is that they are sprayed with liquid lacquer.The application that polypropylene sprays paint, silicon coating and GE electricity varnish (verniX) has all been succeeded.Importantly sprayed on material is checked radioactive contamination, only use to meet the spray coating liquor that activity is less than 0.1pCi/cc.Another kind of practical method is to use by plastics or extremely thin (＜0.1mm) the thin stickup band made of plumbous band.Can use thin bag, best this bag is made by thin beryllium paper tinsel.Yet, use for great majority, by plastics or extremely thin plumbous film make bag or pocket just enough.For the sample of non-self-supporting, rhythmo structure is a kind of very practical method, and it provides desired mechanical property of SR-MPD instrument and radiochemical purity for sample.Because the interlayer that rhythmo structure is formed by the paper tinsel-sample-paper tinsel of roll extrusion between two hot surfaces is usually obtained, and therefore will note not allowing the lamination machine itself be polluted carefully.In addition, note not allowing the paper tinsel of lamination be polluted carefully.

Scanning MPD equipment is described now.In most of symmetrical MPD system, the spatial discrimination ability is suitable with crystal diameter.For low energy X ray emissive source, for example I ¹²⁵, can improve the spatial discrimination ability significantly by the hole of introducing one " pin hole " or " finedraw ".Then, the 2D isotopic distribution can mechanically move between two detectors, and one of them detector has hole recited above.This example is known as the MPD scanner.

It is difficult will obtaining the submillimeter level resolving power under the condition of not losing sensitivity, and this resolving power is to explain that the radiolabeled biomolecule of 2D distributes, for example the vast mole (＜10 in the Asia ^-18Mole) the DNA distribution target on the level is desired.Be used for traditional imager of these application, employed is approximate image-forming principle.For example, in the spatial discrimination detector, for radiator beta-ray, " system resolution ability " depends on the energy of used emissive source, for the source of higher-energy, because the increase " system resolution ability " of the scope of β particle becomes and is on duty mutually.For example, S when with film or a phosphorus imager imaging ³⁵The DNA band of spike is than P ³²The DNA band of spike is more clear, although they detect same DNA band.Therefore, " the system resolution ability " of static system not only depends on intrinsic resolution, and is launched penumbra and becomes quite wide.

The dynamic data that MPD scanner according to the present invention can have superior S/B obtains.It makes the resolving power of system be proportional to the precision that moves at the hole that smears on target or other 2D sample patterned surface.Typically, collimating apparatus (finedraw) width has the identical order of magnitude with amplitude as the feature band width in physical of sample.Static collimating apparatus measurement enters the resultant signal in whole seam district, for example, for the finedraw of a 1mm * 4mm from 4mm ²The signal that sends of sample.This situation and service time are different during resolved detector.Along with collimating apparatus is crossed and is smeared target and move to a new position, make in forward position to be coated with in this zone that target opens wide detector by mobile finedraw, people measure the activity of relative increase or the activity that reduces relatively.On the other hand, some part of smearing target no longer comes out, because this part is blocked by the back edge of finedraw now.Therefore, when when smearing the target imaging, know that time of arrival (toa) carries out the differential deconvolution and calculates smearing target activity and submillimeter level spatial discrimination ability with regard to allowing.The spatial discrimination ability of " system " is proportional to the precision of scanner movements; The MPD scanner can provide about 100 microns degree of accuracy.

When using width as the movable finedraw of X, spatial discrimination ability dX is the magnitude of X/A, A=min{S/B here; Sqrt (N) }, wherein S/B is that the ratio and the Sqrt (N) of signal and background are for the statistical error of a given finedraw position sensing to N photon survey.Usually, S/B＞＞sqrt (N)＞＞10 and dX are about 0.1mm.For the photon of 30kev, particularly for I ¹²⁵, the tungsten paper tinsel of about 200 micron thickness stops and surpasses 90% photon.Therefore, " edge effect " will be limited in resolving power on about 100 microns.For the EC isotope of low energy, this limit can be hanged down to 20 microns.Between the resolving power of MPD scanner resolving power that has improved and confocal microscope similarity is arranged, the spatial discrimination ability is better than the dimension of hole but is with the dimension of hole proportional.

For such system a significantly limitation is arranged; Counting rate has reduced significantly.The best dimension of hole and material depend on the activity of application and 2D distribution target.The lead flake of thickness from 0.2 to 1mm preferably.Typically, for scanning TLC plate and agar gel, be that 2mm and opening length are 2cm with best its A/F of the hole of finedraw form.Acryloyl aldehyde (acrylamide) gel and order to higher resolving power are smeared target, in general, can use to have the long finedraw of the wide and several mm of 1mm.

By using the MPD scanner, the spatial discrimination ability is more much better than the dimension of hole.Typically be the resolving power of 0.2mm.Yet this situation comprises the rewriting of software, and each that moves for machinery in software goes on foot, and all wants the counting rate of calculating optimum.This best counting rate depends on the ratio of signal and background on the given position of 2D distribution target.

Therefore, Zui Jia scan routine is a recursiveness.At first, obtain the image of being added up restriction low precision, constant step size of 2D isotopic distribution target.Thereafter, the scanning that is optimized wherein under the constraint of minimum space resolving power and statistical error, is calculated the acquisition time on each location point so that optimize total sweep time.Operating personnel can select to scan with degree of precision some part of 2D sample.

Counting rate depends on the dimension of crystal in the MPD scanner.A kind of structure of the best is such, and promptly two crystal have different diameters in this structure.That detector of placing hole is less one, and typically its diameter is 0.75 or 1 inch.Second crystal is much bigger, and typically its diameter is 3 or 4 inches.The MPD scanner is not only aspect dimension but also all should be asymmetric aspect the use of different scintillators.For example, when less crystal be that NaI (Tl) and bigger crystal are CaF ₂(Eu) time, the ratio of signal/background can improve about 2 times factor.

The software that is used for the MPD scanner: two detectors that use at MPD scanner according to the present invention are that minor diameter (0.5-1 inch) is used for determining the main detector of spatial discrimination ability and be used to meet/auxiliary detector that anticoincidence is analyzed.The surface of main detector covers with the absorption cover that leaves a hole (normally rectangular slit) (lead or copper become).When scanning, computer-controlled thruster moves sample in the front, slit in the mode of stepping, and its step-length can be equal to or less than the width of finedraw.On each step, all carry out one-shot measurement and reconstitute profile diagram subsequently.

The logical relation of obtaining is as described below.Signal from main detector triggers.Each is carried out shape (being used for background rejection) and amplitude analysis from the pulse of main detector.The peak shape that is recorded to from auxiliary detector the time is also analyzed, and meets/the anticoincidence analysis.In measuring process, set up the power spectrum of forming by all are not rejected in main detector incident and all coincident event.Before sample is moved to next position, to for the counting in the ROI of different isotope settings carries out integration, and result of calculation is attached on the scan-data dish file.

The user interface that is used for the MPD scanner comprises scanning definition module and data analysis module.The scanning definition module allows the user to preset geometric parameter for scanning repeatedly: starting point, scanning step and step number and the Measuring Time (this can be different to different scanning) on each step and for the instruction manual of each scanning.Data analysis module allows (autoradiogram of contour pattern or simulation) by different way to watch scanning profile figure.This module also allows profile diagram is analyzed, and data are delivered to and are used for conventional analysis in the electrical form.

The very scanning MPD of high-space resolution ability is discussed now.In many application, require the spatial discrimination ability of several micron dimensions.MPD with such spatial discrimination ability can improve many biomedical researches considerably, for example, and the research of anatomical and cell.The spatial discrimination ability of MPD scanner is about 100 microns in general.The spatial discrimination ability of all detectors is subjected to down the restriction of column effect: the 1) thickness of radioisotopic 2D distribution target; 2) the restricted stopping power of detector causes parallax (parallaX errors) 3 in crystal) restricted stopping power in hole, cause non-δ transfer function; 4) positioning error in mechanical motion system.

The error of first kind source can be eliminated by use employed similar devices in traditional optical and electron microscope.It is the most basic restriction that causes positioning error that the error of the second kind source is used in the detector that is similar to imaging method at all.This is the major limitation to the spatial discrimination ability of autoradiography or phosphorus imager.As described above, under the situation of radiator beta-ray, limited the resolution of classical detector for the range of all the radioactive source particles except tritium.Clearly, not highly significant a solution is arranged, that is exactly to do scintillator to such an extent that the space resolving power is desired thin like that, but this will cause low-down detection efficiency.

Partly eliminate the problem of particle range with the use of hole imaging.Under the situation of grenz ray, wherein the stopping power of gold or platinized platinum is higher about 30 times and for CaF than the stopping power of NaI (Tl) ₂(Eu) can be up to 100 times, this scheme is attractive especially.Yet, even under the situation of heavy sheet metal, for example gold plaque, platinized platinum, tungsten sheet or lead flake, a big chunk of 27kev photon still can be passed the thin foil of 100 micron thickness.For the film of partially transparent, the software that allows to set up image is brought up to the spatial discrimination ability of MPD scanner for I ¹²⁵Only little of about 50 microns.

Decompose ability in order further to improve, a kind of preferred solution is the energy that is reduced in photon used in the image foundation.In having the EC emissive source of low atomic number, find some elements, for example, Fe ⁵⁶Or Cr ⁵¹In this case, have the photon of about 6kev, as using gold thin film, these photons can be better than on 10 microns the degree of accuracy by imaging.Another kind of method of replacing is to use I ¹²⁵And I ¹²⁵In this situation, not only there is the feature photon (27 or 31kev) of L-layer, but also has the K-layer X ray of 4kev.At last, can also use the Auger electron of launching by the CGX radioactive source of higher-energy.

Under the situation of unusual soft X-ray, for example＜15kev, scintillator is not best detector.People can use and mix the MPD scanner, and one of them small-sized silicon detector covers with the high-density film that has hole.Second detector only surveyed the photon of higher-energy, for example, and at I ¹²⁵Situation under 27 and the photon of 31kev.Therefore, it may be one relatively large, for example diameter is the scintillator of 2-3 inch, for example CaF ₂(Eu).

Another kind method is that a gas detector is used to survey the very low X-ray of energy.By using along the pressure gas of the flow of pore of film, a kind of windowless gas detector can obtain using.This thin slice itself is used as an electrode of gas detector amplification system.

The 4th source of error is the precision of mechanical motion system in the MPD scanner.Piezo mechanical moves the resolving power that there is sub-micrometer scale in generator.In addition, the precision problem of the mechanical part of MPD scanner can be used in those only require the application of relative indicatrix rather than absolute index.

An exemplary spatial discrimination MPD (SR-MPD) is described now.Have the features such as spatial discrimination ability that low price, fabulous sensitivity are become reconciled based on the spatial discrimination SR-MPD detector of scintillator.SR-MPD measure simultaneously nearly 50 use CGX isotope, for example I ¹²⁵The biological material specimens of spike has rational detection efficiency and minimum cross interference (below 1%).Background is that each sample every day is about 0.3% counting.The spatial discrimination ability of SR-MPD is about 2-3mm.SR-MPD can successfully be applied in point-like and smear in the analysis that exist or that be included in the biological products in standard 8 * 12 well shape microtiter plates (microtiter) of target (dot blots) form.

A preferred SR-MPD according to the present invention comprises three parts: auxiliary detector, spatial discrimination detector and data are obtained electronics circuit.Auxiliary detector uses one 3 " CaF ₂(Eu) scintillator, the PMT coupling that the non-space of this a piece scintillator and a low background is differentiated.The performance of auxiliary detector is optimized by diameter and the thickness of selecting crystal, and being chosen in of crystal diameter and thickness provides best trading off between detector efficiency and the low background.Disclosed method also is applicable to here in the MPD of single sample (particular design of selecting, approach the use of quartz window, special encapsulation, the temperature stability of reading electronic circuit, PMT high pressure pedestal of low background PMT).Compare with a set of equipment of commercialization, they have low five times background.The spatial discrimination detector comprises that a diameter is 2-3 " thin NaI (Tl) crystal, the PMT (SR-PMT) of this a piece crystal and spatial discrimination coupling.Preferred SR-MPD equipment is 3 by the diameter that uses Hamamatsu company to make " SR-PMT be achieved.

For a plurality of samples with minimum cross interference are counted, a thick lead cover of about 1mm is placed on the surface of SR detector.The hole cover of the coding of being made by tungsten, gold or platinum allows further to improve the spatial discrimination ability.For example, smearing sample that target arranges as point-like is placed near the hole in cover.This structure makes each detection efficiency of about 50 samples can both reach half of single sample MPD detection efficiency.One of problem is the nonlinear response of SR-PMT.In order to make the maximization of simultaneously measured sample number, can be arranged as sample feasible just big more the closer to the spacing between the outward flange sample of SR-PMT.The price of SR-MPD is about 3 times and can high handling capacity to 20 times be arranged than SS-PMD of SS-MPD price.

For I ¹²⁵, its X ray is very soft.These characteristics allow imaging when one of use has the collimating apparatus of parallel aperture.The use of the SR-PMT that is associated with scanning device can reach fabulous space and originally distinguish ability, can hang down 0.2mm.It is enough that this resolving power is used for nearly all molecular biology.The SR-PMT technology can be applicable to the harsh standard that ultralow radioactivity background is used.In the past, the SR-PMT of the application and development of high count rate is generally 100cpm, and according to the present invention, they can use at counting rate and be lower than in the application of 0.1cpm.Therefore, the radioactivity background of PMT, vibration must be suppressed with noise electromagnetism, the unevenness of spatial discrimination ability and the counterfeit part of making trouble must take in.The model of preferably selecting Hamamatsu to make is the 3 " SR-PMT of R2486.The electronics read-out system of the SR-PMT of Hamamatsu company provides four inputs for the user, can calculate the coordinate of the incident of being detected from these inputs.

The zone that SR-PMT is that an actual diameter is 3 " equipment, be about 2.5 and have only diameter " is the effective coverage, in other words, and the spatial discrimination ability that only in this zone, just can obtain.From the PMT center about 1.1 " the ground square signal descend sharp, on the measured position of the photon cascade in scintillator, for X ray, this will cause the rapid counterfeit part of making trouble.Therefore, for SR-MPD, diameter is that the scintillator of 2 " 2.5 " is hardware and the spatial discrimination ability by using recurrence position calculation software as described below to obtain best and by using.For I ¹²⁵, compare with 32 samples can differentiating with the position calculation software of the electronic circuit of manufacturer and manufacturer construction, this means and can differentiate out 49 samples well.From the viewpoint of background, it is important the diameter much less of crystal than SR-PMT, diameter is 2, and the crystal of the use of scintillator " than using 3 " causes low three times background.Further, using extremely thinly between SR-PMT and scintillation crystal, is that the quartzy couplant of 0.5-2mm helps to reduce because about five times of the background that causes from the β particle of PMT glass emission as thickness.

Alternative SR-MPD instrument is that the diameter of making according to Hamamatsu company is 5 " the equipment made of SR-PMT.Its spatial discrimination ability is than 3 of Hamamatsu company, and " the spatial discrimination ability of SR-PMT is only a little bit poorer slightly.It is than 3 on each detector surface, and " SR-PMT has a lot of resolvable spot of Duoing." SR-PMT is not best for the equipment of low background, 5.Because the implosion that causes of atmospheric pressure, 5 " SR-PMT has used a front glass window that about 6mm is thick, and this glass contains higher K in order to prevent pipe ⁴⁰Impurity, therefore with non-space differentiate 3 " PMT compares, and it causes exceeding about 4 times radioactivity background.5 " the SR-PMT that the bigger the most handy quartz of SR-MPD is done.

The software that is used for SR-PMD: the SR-PMD data are obtained software and must be handled for each incident and surpass two peak shape.The SR-PMT of Hamamatsu company has four outputs, and they are called left signal (SL) in the following description, right signal (SR), last signal (ST) and following signal (SB).In SR-MPD detector hardware, these signal combination are obtained a resultant signal TS=SL+SR+ST+SB together.Therefore, signal obtains and process software is analyzed six signals, i.e. SL, SR, ST, SB, TS and differentiate the signal that triggers electronic circuit (TR) from non-space.Can have very different shapes from the signal of spatial discrimination detector with comparing from the signal of auxiliary detector.From the signal of NaI (Tl) recently from CaF ₂(Eu) signal is faster.Software utilizes this difference can suppress background better.

To with pulse TS and from the pulse TR of auxiliary detector carry out amplitude and shape analysis in case give up electronics with other the counterfeit part of making trouble, and four original signals from SR-PMT are only carried out the amplitude analysis.Be proportional to the energy of particle substantially with the amplitude of pulse, in the hardware of special use, it is carried out and use Analysis of Compatibility between the radioactive source.Yet this signal and the photon incoming position on crystal has dependence, and therefore, after the position of incident was determined, the amplitude of resultant signal was analyzed with energy all incidents outside the energy ROI that presets by software and all is rejected.

Generally speaking, the different mode of hardware and software event analysis can give up to fall this bottom event above 95%.Differentiate at non-space under the situation of MPD, main background source is because the interference that cosmic rays causes, and under the situation of SR-MPD, and main background source is dark current comprehensive among electromagnetic interference (EMI) and the PMT.

Calculate from four output signals of SR-PMT the position of incident on detector surface.First approximation is by X _o=(SL-SR)/TS and y _o=(ST-SB)/TS provides.Yet this is approximate to have only when incident is incident near the position of germ nucleus effectively, and on the edge of crystal, the counterfeit part of making trouble of important position is arranged.Therefore, preferably use the position of recurrence to search routine, wherein real position is determined from following formula: and

y _i=(c[y _I-1] * ST-d[y _I-1] * SB)/TS must determine by the method for experience for each SR-PMT scale function a (X), b (X), c (y) and d (y).Unfortunately, this function also depends on the energy in source.In data acquisition, set up the 2D image corresponding with detector surface.Follow closely obtain after, to the counting integration in the zone relevant in cover,, be converted into dpm by this digit rate of calibration data then all to draw its counting rate for each sample with hole.

In the process of equipment scale,, determine with the corresponding image section of hole, detection efficiency with corresponding to the background numerical value of each hole by the sample of known activity being put into hole, obtaining image and analysis image.Automatically carry out the cover arrangement of software by the software that uses direct peak detection routines.

The MPD imager is described now.MPD imager based on scintillator has cheap price, superior sensitivity, features such as the spatial discrimination ability of high handling capacity and submillimeter level.MPD imaging X _i=(a[X _I-1] * SL-b[X _I-1] * SR)/the TS device can be used in the biomaterial of quantitative measurment fractionation (fractionated), for example, and chromatogram output, dna sequencing gel and smear.The spatial discrimination ability of MPD imager can meet or exceed 0.2mm.

The MPD imager allows at the resolving power of submillimeter level and is applicable to the quantitative test that fractionation is exported, for example, and sequencing gel or chromatograph plate.In this equipment, SR-MPD and a high-precision 2D thruster link together.Height distinguishes that ability obtains by using mushy pattern; Each incident is assigned to space ROI neutralization reconstruct from known angle of rake position and comes out.The MPD imager than phosphorus imager sensitivity Duo and faster, the phosphorus imager obtains application more and more widely in molecular biology.The dna sequencing smear is distinguished on several Zeptomole levels by quantitative measurment and point/bar pattern by the MPD imager three-dimensionally.

A preferred L PD imager comprises following subsystem: 2.5 " NaI (Tl) scintillator, " spatial discrimination PMT is connected with 3; 3 " CaF ₂(Eu) scintillater is read with the PMT of low-activity background and to be connected; Hole/the isolated body of a coding/screened room subsystem; A 2D impeller system has the relative motion precision of about 100 μ m; Read electronic circuit, comprise three DSO 58 plug-in units; Data are obtained/analyzing subsystem (for example, Pentium 90MHz).

The MPD imager allows dynamically to obtain information with superior S/B.It makes the resolving power of system be proportional to precision in the lip-deep aperture motion of smearing target.Typically, collimating apparatus (slit) width has the identical order of magnitude with the physical width of DNA band.The collimating apparatus measurement of a static state enters the resultant signal of whole gap area, for example, and for the finedraw of a 1mm * 4mm, from 4mm ²Smear the signal of target.Situation can be different during resolved detector when service time.Along with collimating apparatus is crossed and is smeared target and move to a new position, make in forward position and to smear in this zone that target opens wide detector by mobile slit, people measure the activity of relative increase or the activity that reduces relatively.On the other hand, some part of smearing target no longer comes out, because this part is blocked by the back edge in slit now.Therefore, when when smearing the target imaging, know that time of arrival (toa) allows the differential deconvolution of the spatial discrimination ability of smearing target activity and submillimeter level is calculated.The spatial discrimination ability of " system " is proportional to the degree of accuracy of scanner movements; The MPD imager has about 100 microns degree of accuracy.

The intrinsic resolution ability of MPD imager is discussed now.This parameter can produce a series of clear pattern by using " radioactivity " ink in the HP ink-jet printer, makes MPD imager and phosphorus imager compared to measure.Used one every square centimeter relative more equal surface activity as 10pci.Test pattern is that the horizontal bar of 3mm, 2mm and 1mm is formed by the length that keeps equidistant from distance, and the spacing between the bar equals the width of bar.Pattern and its image obtain by the phosphorus imager of MPD imager and molecular dynamics type.Through after 48 hours irradiation, the phosphorus imager detects the pattern of 3mm well, although background is quite high.It can only partly tell the pattern of 2mm, and surveys to come out fully for the pattern of 1mm.On the other hand, MPD imager even clearly tell the pattern of 1mm, its S/B is about 10.0.5mm image also can distinguish, but need long sweep time.

The software of MPD imager: the MPD imager has made up the function of SR-MPD and the function of MPD scanner.A round crack is arranged leading covering on (SR) detector on the cover, it has determined the spatial discrimination ability of imager.The 2D sample is placed on by on the computer-controlled thruster, and this thruster can be put into sample in the measuring position in order.In each position, counting is finished (use with SR-MPD in the used identical logic of obtaining) in a time of presetting.To all holes all obtain counting rate and counting rate be stored in one the dish file in.

Be right after after the scanning, from enumeration data, re-construct image.The pattern of apertures of determining resolving power is such, and in order to obtain a continuous images, these points must intersect at directions X and Y direction.Pattern should allow mutual intersection, although and unnecessary necessary each other vertical.For each resolution mask that is suitable for, there is an independent scale file that comprises the software mask in system, is used for the distribution of hole is mapped on the imaging surface.This mask is automatically constructed by software in the scale process.

User interface allow to be selected the rectangular region of a scanning and for each aperture position point preset count time.Data analysis module is reconstructed image from counted data, allow to watch image with auxiliary color, shades of gray, circle of equal altitudes or as modes such as 3 dimension figure surfaces, and with many kinds of standard format memory images so that analyze with other image processing program.

A large-scale MPD imager is discussed now.For large-scale MP imager, the spatial discrimination partial design of system is paired in big 2D fractionation output can have higher handling capacity.The commercial value of MPD imager depends on the handling capacity that provides enough big, and big arriving can be 10 ^-19On the level of mol to 2D gel target with smear target and analyze round the clock.In order to reach this requirement, can use the MPD imager of big zone (for example 12 inches * 8 inches).

Can use three types of large spaces resolution gamma ray detectors in large-scale MPD imager to be: to use the detector of one or several SR-PMT, in the Auger camera architecture, use the detector of dozens of minor diameter PMT and the detector of use microchannel plate and CCD (charge-coupled image sensor) imager.Use a kind of preferred novel scintillator, the yttrium aluminium calcium titanium crystal (YAP (Ce)) of the cerium that promptly mixes can be made the large-scale MPD imager with very high spatial discrimination ability and extremely low background.

The useful feature of large-scale MPD imager is: 1) minimum as far as possible radioactivity background allows the sensitivity of Zeptomole magnitude in many biological applications; 2) allow the instrument of high-throughput, even for the unusual sample of low-activity; 3) at a low price, user-friendly equipment, have the software of convenient biological applications.

In example of large-scale MPD imager according to the present invention, in the time of four spatial discrimination subelements of an independent computer control and co-operating.In the application of target, by relatively low counting rate, promptly arrive between the several countings of per minute tens of per seconds for its counting rate of each aperture position, make it become possibility.Time and analysis time that pulse shape analysis only use takes about 100 μ s can be reduced to about 10 μ s.In different detectors since the accumulation of incident cause lose and can be solved completely.

The restriction of factor below the quantity of detector is subjected in the device of multidetector: the handling capacity of DSO 58 data data buss, comprise the pulse shape analysis time of the speed of control microprocessor, the quantity and the price factor of available data bus notch.For example, the MPD of one four detector can be connected with the mainboard with 12 bus notches with the Pentium 120MHz in the full-tower structure.Four SR-PMT can be multiplexed in the independent computing machine.

Large-scale MPD imager based on several SR-PMT: this exemplary embodiment has four modules: the * auxiliary detector; * the spatial discrimination detector that constitutes by four subsystems; * mechanically-propelled device assembly; * data are obtained and processing unit.

Auxiliary detector is based on CaF ₂(Eu) scintillator, scintillator and one group of PMT coupling through background that select, low.Preferred auxiliary detector module is as described below, and " PMT is coupled, and this is a simplest and the most cheap a kind of instrument, but it causes sizable equipment by the suitable photoconduction of use and one 6 for the first, big as 8 " * 8 " crystal.The second, one independent CaF ₂(Eu) scintillator and a PMT array are coupled, for example, one 9 " * 9 " scintillator can with 9 form coupling 3 " the PMT array is coupled.The three, one 8 " * 8 " scintillation crystal and 16 couplings 2 " the PMT array is coupled.The output of all PMT is added together and analyze by the low noise electronic circuit paired pulses height and the pulse shape that comprise DSO 58.Suitably the pulse of amplitude can be used as obtaining and analyze the triggering from the data of spatial discrimination detector.

Preferably use PMT with supporting electronic circuit " coupling ".When given energy particle excitated, the amplitude of pulse should be identical with shape basically.For example, it is identical that time delay should keep in the scope of 100ns, and pulse height should keep identical in 10% scope almost be the same with the shape of pulse.Requirement for the PMT that satisfies coupling triggers detector and can be made up of four sub-assemblies, each by with single 4 " PMT be coupled 4 " * 4 " CaF ₂(Eu) crystal is formed.

But the shape of PMT preferably square or hexagonal columniform PMT can be used in suitable polypropylene (acrylic) waveguide and carry out optically-coupled.In four 4 " * 4 " detector amalgamations situation together, replace effort the PMT coupling be to use much simpler computing machine scale.Yet the unevenness of scintillator detector is always maximum near the edge of scintillator, that is to say, amalgamation (mosaic) type trigger detector have lower a little detection efficiency and a bit weaker energy resolution, it is from the negative effect background.

NaI in scintillator (Tl) is because its good stopping power and best energy resolution and can access use.An exemplary large area space resolved detector module has the effective coverage of 8 " * 6 ", allows imaging is carried out on the whole surface of typical sequencing gel target.An exemplary amalgamation SR-detector has used four less SR-PMT.Detector assembly comprises four spatial discrimination detector modules, and each NaI by one 4 " * 3 " (Tl) crystal is formed, and the signal of crystal is by the square SR-PMT output of Hamamatus company.By square SR-PMT the effective coverage of a 60 * 55mm is arranged, wherein desired spatial discrimination ability is 2-3mm.Preferred foursquare rather than circular 3 " SR-PMT is because squarely have a better surface coverage.Electronic circuit and imaging characteristic square and circular SR-PMT are much at one, therefore can use identical electronic circuit and software basically.

In order to save the notch that can be used for control computer, all electronic circuits that are used for a single SR-PMT preferably are installed in a single plug-in unit.Large-scale MPD imager adopts the multiplexed quantity of electronics plug-in unit that reduces so that conserve space helps the processing of load heating problem and the price of reduction equipment.

The use supposition of single Pentium 120MHz is for two detectors, and promptly for four passages, an independent standard length plug-in unit comprises signal Processing and coincidence circuit.Even one have the mainboard of 12 notches also to lack enough ISA notches, because DSO 58 performances have two passages on each plug-in unit.A preferred DSO plug-in unit 58 has four passages, and each is 50MHz.Depend on cmos element and can reduce heat dissipation widely.Then, four of DSO passages can be complementary with the plug-in unit of an independent standard length with pci bus.

The multiplexer channel electronic circuit is preferably with eight thresholds and provides mark for software.For each detector, have independently to postpone and coincidence circuit, allow to carry out non-meeting and coincidence counting.Then, 40 marks of a cover (for each SR-PMT, have eight thresholds outputs, four meet signal and for the output of four thresholds of signal) understood to computing machine and allowed to carry out online event reconstruction.To being passed among three DSO from the signal summation of all SR-PMT with output signal.DSO allows to utilize existing software to carry out the pulse shape analysis.Consider the availability of a four-way DSO, having only three members is essential to the information of handling from 4 SR-PMT.So that handle data from two SR-PMT, having only two 4-passage DSO plug-in units is essential to the information of handling about the pulse height in SR-PMT (summations of all 4 outputs) and non-space resolution PMT by the polarity encoding.

In order to control heat load, several electric fan plug-in units can be placed between DSO and the SCPC.Show at equipment under the situation of sample-out count every day that problem that the electromagnetic interference (EMI) from electric fan plug-in unit (two interchange (AC) motor is arranged on each plug-in unit) causes is suitable difficulty, still can use suitable electric shield cover that electromagnetic interference shield is fallen.Cooling unit according to Peltier (Peltier) effect (non-alternating current) provides less difficult scheme.

Consider the non-effective coverage between the detector cells, software preferably allows " seamless " image reconstruction and is consistent with use based on the computing machine of Intel P6 processor.

Require pulse shape analysis faster to several detectors implementations based on SR-PMT are multiplexed with big area detection device of construction.In the system of single detector, have long pass and send these DSO of time (each pulse is 200 μ s) enough.Large-scale MPD imager uses the DSO with very fast computer interface.Utilize this advantage to require the burst process of fast-loop driver and acceleration fully.Therefore, by considering that the logical relation that pulse shape suppresses for multiplexed system is optimised from the additional information of all PMT and the order of change test.The further optimization of pulse shape code analysis obtains by utilizing efficient n ative (this locality) Pentium computer and P6 instruction.

Because the target of MPD is that quantitative measurment/imaging is carried out in trace-level activity tagging, explanation is important for correction data from the statistical study of the data of the ratio (S/B) of the relatively poor signal of having of radioactive source and background and bigger error.Therefore, preferably include software statistics analytic function and routine, be used for image enhancement and identification for image enhancement and identification MPD imager.The latter is preferably according to the AI technology the recurrence method that resembles analog neuron net and/or storage matrix.

Large-scale MPD imager according to the time delay technology: some limitations of large-scale MPD imager are relevant with used SR-PMT: because the Hamamatsu pipe is subjected to K ⁴⁰Efficiently the penetrating property background that causes of pollution and because four scale difficulties of causing of the big dead band between the SR-PMT independently.

The Anger video camera is an a class large-scale gamma ray detector commonly used, and the surface distributed of wherein independent big NaI (Tl) crystal many photomultipliers.When a photon was absorbed by crystal, light was shared between several PMT.Have four PMT of peak signal and come the reconstruct incident by searching, determine the center of gravity of light pulse from their ratio of signal amplitude.The spatial discrimination ability is subjected to the restriction of the factors such as number of crystal thickness, photoyield and used PMT.Typical A nger camera parameters is: Na (Tl) crystal thickness=0.5 inch, quantity=36-64 of PMT; Intrinsic spatial discrimination ability=2-3mm.For I ¹²⁵, crystal thickness can be reduced to 1.5mm, and this thickness can improve the spatial discrimination ability, to being low to moderate 1mm.In the simplest example, and the quantity of ADC and the quantity of PMT (as 24 2 " PMT) be identical.According to the present invention at this on the one hand, can design complicated more scheme, wherein can use a large amount of thresholds, be essential but have only 8 ADC passages.Preferably select MPD imager, but desired electronic circuit is quite complicated and because the big quantity of passage, the pulse shape analysis is difficult to realize based on the Anger video camera.

An alternative embodiment is to use pulse daley technology and DSO to differentiate sub-ray detector and novel scintillator material with the hiperspace of reconstruct photon position, the yttrium aluminium calcium titanium crystal (YAP (Ce)) that Ce activates.It provides high photoyield (be approximately NaI (Tl) 50%) and than fast about five times of NaI (Tl).In addition, can use and the DSO plug-in unit of Intel Pentium or P6 and the hyperchannel that holds, high-speed and large memories two passages for example, 150MHz/ has the passage of 32kb storer from Gage company.

Be common the time delay of analogue delay unit from tens ns to several μ s of low decay.Have triangular shaped YAP pulse (rise time is that 10ns and fall time are 50ns), a passage that can enough DSO up to the output of 10 PMT carries out digitizing.Therefore, two DSO plug-in units can be to the output encoder up to 40 PMT, and allows the quantification of 8 of the nominals of very high reliability.We can use mould 4 coding, wherein each of four adjacent PMT is encoded in the different DSO passages.Therefore, might make a relatively inexpensive pocket Ager video camera.

When using the YAP scintillation crystal in the MPD imager, signal pulse has the duration of about 50ns.By using this duration of constant delay that the signal from several PMT is multiplexed in the single DSO input.Preferably to 6 output summations, this output is from each row of 4 row PMT and respectively through 0,100,200,300,400 and the delay of 500ns.Then, this train of impulses is admitted to a DSO input channel neutralization and sends in the triggering plug-in unit (SCPC), triggers plug-in unit all DSO in the system are produced trigger pips.For second (meeting) detector, NaI (Tl) crystal of same size (12 " * 8 ") is " PMT read output signal by four 3.Output summation and signal to these PMT are used to determine whether incident is coincident event.In addition, this pulse is carried out the pulse shape analysis to suppress background.SCPC is all passed through in all thresholds, digital delay and gain under software control.Computing machine is decoded to the desired multiplexed signal of DSO and is sought the coordinate of each tested incident by analyzing pulse height in all 24 PMT.

Problem for fear of the radioactivity background, large-scale MPD imager uses through the PMT that carefully chooses, and this PMT that selects is according to factors such as radioactivity background, detection efficiency, energy resolution, the lip-deep homogeneity of photocathode, dark current and long stability.Preferred photomultiplier comprises 1 " or sexangle 2 " PMT that EMI company makes.For one 12 inches * 8 inches MPD imager, preferred structure is that the spacing between Center-to-Center is 2 " sexangle 2 " PMT arranges the mesh shape that forms, and PMT is arranged in 6 * 4 arrays.Another kind of alternative structure choosing is, for " the 1 " PMT that is 1.5 of the spacing between the Center-to-Center, preferably PMT is arranged in 8 * 5 formation." PMT, its price is quite cheap, because electronic circuit is quite simple, and only needs two DSO plug-in units for 2.On the other hand, 1 " PMT provides good slightly spatial discrimination ability and approximately hangs down 2 times radioactivity background.

Large-scale MPD imager preferably uses special-purpose data to obtain and process software.From the signal of several PMT by using lag line and be encoded and being multiplexed in the DSO passage.Obtaining software uses suitable pulse shape to give up and baseline recovery routine processing consecutive pulses.Whether although be simplified the constant time delay that this service aisle is crossed between the signal, still needing the pulse in " string " is to be caused by an independent incident to carry out extra consistency analysis, even need the calculating of some deconvolution.Preferably select to handle reliably and efficiently from the coordinate of each incident of data computation of a plurality of PMT for basis.For storage with handle googol, and, take special measure to inevitable heteropical correction in the big regionally detecting device according to amount.Calculate by replace great majority with the search form, encode, calculating is limited in them in the scope of integer arithmetic computing as much as possible and use the method such as assembly language can these programs of optimization, to reduce the dead time.On the other hand, employed in the SR-MPD system of burst process, analysis of spectrum and image reconstruction and single detector is identical.

Order sample MPD equipment: ssMPD is 12 samples, desk-top radiation counter, it can be used for to multi-photon radiation isotope comprise the 125I emission the photon survey per minute counting and calculate the decays of per minute.In 0.05 to 2.0ml the volume in the sample tube that is included in 12mm * 75mm or 13mm * 100mm, the decays of measurement is in 1 to 106dpm scope.Sample tube is sealed to avoid pollution detection device chamber.

The layout of ssMPD is presented among Fig. 6.Test tube holder 70 is installed on the test tube gearing 71 of level, and test tube gearing 71 slides on lead shield plate 72.Two detectors 73 are installed in the face of isolated body 77, and each detector comprises a scintillator 74, a PMT 75 and a pedestal electronic circuit 76.Each of sample tube (not drawing among the figure) is fallen and promoted to vertical test tube lifter 78 successively.Detector and mechanical part are supported by support 79, and entire equipment is surrounded by shell 80.

This detector assembly is a double detector system that comprises two scintillator crystals, each scintillation crystal and a high-resolution plane photomultiplier coupling.Detector assembly is encapsulated in the composite shielding chamber of being made up of lead-Xi-copper minimum so that the background of environment is dropped to.Except allowing to count effectively the gamma-ray projector, sample fixer plays the effect of isolated body so that the phase mutual interference between the reduction twin scintillator detector assembly.

This detector assembly directly is connected with a personal computer (PC), and personal computer (PC) is furnished with ssMPD and reads electronic circuit, Windows ^TMControl under the environment and data logging software and a printer (choosing wantonly).Software outputs on the printer or is passed in the file a general report leader with about counting, the per minute decays that calculates and statistical error that sample number, sample position, gate time, the per minute of each sample records.In addition, software is supported various commercial data analyses and is identified that the data of interpretation software bag export.

For ¹²⁵I, the specific region of energy and detection efficiency is automatically set up in the scale process.For other isotope, counting carries out under restricted energy and pulse-shape discrimination (promptly will be higher than background) condition and absolute detection efficiency is unknown.If wish to draw non- ¹²⁵The absolute activity of I sample, the operator may need this isotopic scale to be studied source of crossing and the detection efficiency of setting up about this isotopic ssMPD.

The ssMPD system uses a pair of scintillator crystals that has photomultiplier (PMT), and photomultiplier (PMT) is as the readout equipment of gamma-rays and X ray emitter-detector.Read amplification of electronic circuit and software and shaping signal, analyze pulse shape and set up the power spectrum of a combination for use in later pulse height analyze from each PMT.

The exterior shield chamber of ssmPD detector minimizes the effect of environmental radiation, and therefore, the principal ingredient of on-radiation background is because the dark pulse among the PMT causes.The shape of these pulses is different from the shape that is produced by the scintillator in the detector, therefore can give up to fall the counterfeit part of making trouble of PMT dark pulse and most of electromagnetism and vibration.Based on after the giving up of pulse shape, the background in the system almost is smooth and highly stable in the energy range of 15-100kev, with near the radioactivity the detector irrelevant the hard gamma-ray radiation of ssMPD screened room (can penetrate except).

For desired isotope the counting of not giving up in suitable energy area is sued for peace to determine counting rate.The actual activity (per minute decays or dpm) that counting rate (cpm or cpm) is converted to sample need be known the detection efficiency (DE) corresponding to specific radio-label counter.

To determine respectively two detectors each detection efficiency (DE) so as to improve the scale of ssMPD and precision so that the integrity of test macro and so that by the position deviation of two estimated value correcting sample fixators of the actual activity of scale sample relatively.

A direct indicator of the sensitivity of ssMPD (to the restriction of surveying) is that the activity (BEA) one of its background equivalence is defined as the radioactive source activity that produces the counting rate that equates with background in the detector.This performance index has been considered background and two factors of detection efficiency of ssMPD.For ssMPD background equivalence activity is 2pci, or is equivalent to the 125I of 1 pmol, and keeps comparable detection efficiency (DE is 50%) and obvious low radioactivity background (BKG is 2cpm).

SsMPD background Rejection technology allows from 1 to 10 ⁶The reliable quantitative measurment of cpm (6logs dynamic range).10 ⁶Cpm is above non-linearly to be caused by the pile-up effect in the detector.Although the response in this scope no longer is linear,, the dead time of the system that obtains of ssMPD is expansion not, therefore, still can count, and the result who measures is carried out the pile up effect correction get final product.

Another desk-top embodiment has the robot arm that can pick up and place, and it picks up selecteed sample from specimen holder, and sample is put into sample fixer, and it shifts out sample and sample is put back on the origin-location when finishing counting.In these two desk-top embodiment, the moving machinery part is coupled so that make the sample-in counting interval optimization with data processing equipment.

Generally speaking, photon detector of the present invention as can be seen provides many advantages.These advantages comprise low background and high sensitivity, high detection efficiency, high energy resolution, superior repeatable and stable, cheap price and less size.

Though these descriptions have comprised many concrete details, should not be interpreted as restriction to these to scope of the present invention, but as the demonstration of preferred embodiment.Might there be many other modification.Scope of the present invention is not limited by described above and illustrated embodiment, but below comprise that claims of wideer explanation of its equivalent are determined.

Claims (53)

1. radioisotopic device that is used for surveying in the sample, comprise (a) detector assembly, comprise gamma-rays/X-ray detector of establishing relatively, radioisotopic radiation in being used for surveying when on the sample supporting base that sample is placed between the detector from this sample, with being used for radiation is converted to electronics output pulse, (b) pulse-shape analyzer, become work to be connected with detector, be used for analyzing described output pulse and itself and predetermined acceptance standard are compared, give up and do not satisfy this predetermined pulse of accepting standard, satisfy the output pulse that this accepts standard with counting, described counting is for meeting the corresponding pulse of radiation and carry out respectively with meeting with non-.

2. according to the device of claim 1, wherein said detector assembly comprise at least two detectors of relatively establishing wherein at least one detector comprise a thin inorganic scintillator crystal, in the time of above impinging upon from radioisotopic photon radiation, this scintillation crystal produces a signal; Be placed on the isolated body between the scintillator; The mask array that scintillator and external radiation are separated; With the optical sensor of an amplification from the signal of this scintillator.

3. according to the device of claim 2, wherein said scintillator is from by NaI (Tl), CsI (Tl), CaF ₂(Eu) and choose in the crystal group of composition such as YAP.

4. according to the device of claim 2, wherein said each scintillator is that thickness is less than about 0.5 inch identical CaF ₂(Eu) crystal.

5. according to the device of claim 2, wherein said optical sensor is the photomultiplier of being made by the low-activity material, has the radioactivity that is less than about 10pci.

6. according to the device of claim 5, the diameter of wherein said photomultiplier is about 2 " to about 3 ", and the diameter of described scintillator crystals is than the diameter little about 7% to about 25% of described photomultiplier.

7. according to the device of claim 2, the optically transparent window of one of them low radiation background is arranged between described scintillator and the optical sensor.

8. according to the device of claim 7, wherein said window comprises quartzy or a kind of high density (＞4g/cc) and the optically transparent material of high atomic number (greater than about 50).

9. according to the device of claim 7, wherein said window is by from making with select material next group material: comprise highly purified GeO ₂Or contain germanite glass, leaded high-density glass, PbF ₂With unadulterated Zhe Suan (BGO), be to use with the optics oil of PMT optical characteristics coupling to be connected optically with optical sensor with described scintillator with wherein said window.

10. according to the device of claim 5, wherein said scintillator and photomultiplier are to be covered by at least three layers of opaque plastics band that one deck metal strip is arranged thereafter successively.

11. according to the device of claim 10, wherein said metal tape comprises that the metal tape of special high magnetic permeability and whole assembly are covered by several layers of copper strips.

12. device according to claim 1, wherein said detector assembly is placed in the screened room, to have a kind of composition in this screened room material at least be atomic number greater than about 61 metal, perhaps compound wherein has the density greater than about 5g/cc, and the screened room material is chosen as the radioactivity background that is less than about 10pci/g.

13. according to the device of claim 1, sample supporting base wherein is a vinyl disc, its dimension arrives between about 75 * 100mm at about 12 * 13mm.

14. according to the device of claim 1, wherein said two detectors comprise that thickness is less than about 5g/cm ²Semiconductor detector.

15. according to the device of claim 1, wherein said two detectors are gas detectors, one of two detectors are the spatial discrimination detectors.

16. device according to claim 1, wherein said sample supporting base comprises the sample point of an encapsulation, and thickness is sufficiently thin and made by the material of the atomic number of enough low density/enough low, the X ray quantity that makes this sample supporting base absorb can be ignored, and also can the pollution detection device.

17. according to the device of claim 16, wherein said sample point is encapsulated among the material of skim, this material has and is less than about 0.1pci/cm ²Low-down radioactivity background and low atomic number.

18. according to the device of claim 17, wherein said encapsulating material from choose, comprise spray with next group material, spray paint, acrylic coating, organic silicon resin paint and GE varnish.

19. device according to claim 17, wherein this sample is on firm, the flat thin slice that is attached in the envelope, its by make from the film that chooses material with next group, it comprise thickness less than the beryllium film of about 1mm, thickness less than the plastic foil of about 0.5mm and thickness aluminium film less than about 0.2mm.

20. the device that is used to scan according to claim 2, one of wherein said scintillation detector is significantly less than another scintillation detector, the heavy metal film that further comprises a high density/high atomic number has a fine porosity to be positioned at the front of this little detector on this heavy metal film.

21. right according to claim 20 ¹²⁵The optimized scanister of I radioactive source, wherein said scintillator is CaF ₂(Eu) crystal, crystal thickness are less than about 3mm, and diameter is between about 0.5 inch to about 1 inch for small crystals, and diameter is between about 2 inches to about 3 inches for megacryst.

22. according to the scanister of claim 20, wherein said pulse-shape analyzer has two kinds of patterns, OR pattern and AND pattern, and the OR pattern receives non-coincidence impulse and coincidence impulse is counted, and counts and the AND pattern receives only coincidence impulse; Further comprise one be applicable to the fixed sample supporting base and on the bidimensional dimension sample thruster of mobile example supporting base, it has enough spatial discrimination abilities that the sample on plane basically is placed in the hole of little scintillation crystal front; With a controller, be used to discern the angle of rake position of sample and allow related to each position and counting rate; When optimizing time that data obtain data for each sample position and reach the ratio of the ratio of prearranged signal and background or signal and statistical error, can stop to obtain of data with the box lunch accumulation; With pulse-shape analyzer and controller the image that the data of obtaining make bidimensional is shown.

23. according to the scanister of claim 22, wherein sample is carried out rescan, for the first time with the scanning of low spatial resolving power be lower than in the zone of a predetermined numerical value with the scanning of higher spatial resolving power at selected counting rate for the second time.

24. according to the scanister of claim 21, wherein said its thickness of little scintillator is less than about 0.1mm, its to Auger electron or very the X ray of low energy (E＜10kev) is sensitive and diameter between about 0.1 inch to about 0.5 inch arranged.

25. according to claim 20, right ¹²⁵The optimized scanister in I source, wherein said little detector is the silicon scintillator or the spatial discrimination ccd detector that are thinner than 0.1mm, it is to Auger electron or the unusual low energy X-ray (sensitivity of E＜10kev), and diameter and described big scintillator between about 0.1 inch to about 0.5 inch are arranged is CaF ₂(Eu) crystal, its thickness is less than about 3mm, and diameter is between about 2 inches to about 3 inches.

26. device with spatial discrimination ability according to claim 1, wherein at least one detector comprises a thin NaI (Tl) scintillator, wherein there is a high density/heavy metal film to stick on this scintillator, the pattern of apertures that coding is arranged on this film, wherein this scintillator with have the spatial discrimination photomultiplier of a plurality of outputs to be coupled, each of these a plurality of outputs all is connected with the low noise amplifier that is complementary effectively, generate one and output and output single and summation is input in the multiple tracks spectralyzer with the output of electronics mode pair amplifier summation.

27. device according to claim 26, with wherein from spatial discrimination PMT through the output pulse of amplifying and " standard shape " pulsion phase of accepting standard according to pulse shape relatively, and in the PMT that spatial discrimination and non-space are differentiated, have only the incident of satisfied " standard shape " condition just to be received and to be used to set up the sample image of bidimensional.

28. according to the device of claim 6, wherein said spatial discrimination photomultiplier has the position of four outputs and the incident of X-ray to come out by iterating algorithm computation, first approximation is by X _o=(SL-SR)/TS and Y _o=(ST-SB)/TS provides with the i level is approximate and tries to achieve by following formula: X _i=(a[X _I-1]) * SL-b[X _I-1] * SR)/TS and Y _i=(c[Y _I-1]) * ST-d[Y _I-1] * SB)/TS SL=left signal wherein, the SR=right signal, signal under last signal of ST=and the SB=, TS=SL+SR+ST+SB, wherein a (X), b (X), c (y) and d (y) are the scale functions, determine with empirical method for these functions of spatial discrimination photomultiplier.

29. according to the device of claim 28, wherein the actual energy value of X-ray is calculated from the incoming position of X-ray by using the graduation apparatus of determining for the effective empirical method of spatial discrimination photomultiplier transit of searching.

30. according to the imaging device of claim 26, paste the aperture mask of a coding on wherein said NaI (Tl) crystal, this mask is made by the film of high density/high atomic number, and has the regular pattern that reaches 50 apertures or slit; The sample supporting base comprises the bidimensional sample array on a plane; Further comprise a computer-controlled thruster, measuring position one time of presetting of stop of aperture mask front put into sample successively by this thruster.

31. according to the imaging device of claim 30, further comprise an imaging analysis device, wherein image is to re-construct out from enumeration data; The pattern of apertures of determining resolving power is such, and in order to obtain continuous images, described pixel position must along directions X and the Y direction be intersected mutually and described pattern makes mutual intersection become possibility; For each available resolution mask, there is an independent scale element that comprises the software mask in this system, and this software mask is used for determining hole is mapped on the imaging surface; User interface allow to be selected a rectangular region to be scanned and for each pixel preset count time; Data presentation system allows to watch described image with auxiliary color, shades of gray, circle of equal altitudes or as the modes such as surface of a 3D, and with many kinds of standard format memory images to analyze with other image processing program.

32. according to the device of claim 1, one of wherein said detector is to surveying Ge semiconductor detector, silicon detector or a spatial discrimination gas detector of X-ray the best.

33. according to the device of claim 32, wherein said spatial discrimination detector is a thin cloud chamber from restriction, wherein said spatial discrimination ability obtains with the ccd video camera imaging.

A 34. radioisotopic gamma-rays and x-ray photon method for transmitting of from background radiation and noise, screening in the sample, comprise: sample is put on the sample supporting base, and what this sample supporting base was clipped in that opposite face is provided with is used for surveying between the detector of gamma-rays and X ray; Gamma-rays of surveying with at least two detectors of launching from this isotope and X ray are converted to electronics output pulse; Described output pulse is counted and time measurement; Described output pulse amplitude is normalized within a predetermined scope on the baseline, and the energy of emission is carried out association; When existing one to trigger the output pulse, when promptly exporting the amplitude of pulse, produce one first trigger pulse above a predetermined threshold value; With when having the triggering output pulse of two whiles, when promptly the amplitude of these two output pulses surpasses predetermined threshold value, produce one second trigger pulse; With give up the pulse that pulse height surpasses predetermined threshold; In response to trigger pulse, capture predetermined quantity order by normalization the output pulse; According to predetermined isotope relevant with system accept the captive output pulse of standard analysis; Satisfying this with counting accepts the pulse of standard and gives up and do not satisfy the pulse that this accepts standard.

35. device of from background radiation and noise, screening the radioisotopic emission in the sample, comprise: the device that is used for fixing sample, it is clipped between the device that converts electronics output pulse from this isotopic emission to, be used for device with time measurement is counted in the output pulse, be used for output pulse amplitude normalized within a predetermined scope on the baseline with energy to emission and carry out related device, the device that is used for following operation: when existing its amplitude to surpass the output pulse of a predetermined threshold value, produce one first trigger pip; With when existing two basic amplitudes separately simultaneously to surpass the output pulse of predetermined threshold value, produce one second trigger pip, and give up the output pulse that pulse height does not have to surpass this predetermined threshold; Be used in response to a trigger pulse capture predetermined quantity order by normalization the device of output pulse, with be used for according to predetermined isotope relevant with system from one group by pulse shape, pulse height, coordinate with meet the device that the acceptance criteria analysis that chooses the factor of forming is captured the output pulse, be used for counting the pulse of satisfying this isotope of being scheduled to accept standard relevant and give up and do not satisfy the device that this accepts the pulse of standard with system.

36., further comprise being used for device that described detector and radioactivity background are shielded according to the device of claim 35.

37., further comprise the device that is used for absorbing most of outside X ray according to the device of claim 35.

38. according to the device of claim 1, wherein said sample supporting base has a plurality of bellmouths, these apertures are aligned to the pattern of easy resolution, and sample that will be to be studied is placed in described these apertures.

39. according to the device of claim 38, wherein said sample supporting base with the aperture in the sample supporting base according to described isolated body in the essentially identical pattern of the little sectional hole patterns sample that will spread upon on the suitable film line up.

40. according to the device of claim 39, wherein said sample supporting base has two parts, each part has identical little sectional hole patterns, and the film of being smeared is between these two parts.

41. according to the device of claim 1, each detector of wherein said detector assembly all comprises a prime amplifier, amplifier and shaping amplifier.

42. device that meets gamma-rays/X ray (CGX) of the emissive source in the quantitative measurment sample optionally, comprise: (a) be used for surveying from the CGX emissive source, launch meet gamma-rays and X-ray device as the output pulse of each radiation detector, (b) be used for analyzing from the shape of the output pulse of each detector and the device of amplitude, (c) be used for screening and give up the non-device of exporting pulse that meets, (d) be used for screening and give up vacation and meet the device of exporting pulse and the device that (e) is used for utilizing the content of CGX radioactive source in the remaining output pulse quantitative sample.

43. according to the device of claim 42, can survey be less than 1 vast mole by the molecule of spike.

44. in being coupled with the programmable device that receives the output signal that when ballistic phonon is incident on described at least one detector, produces with at least one detector work, its method comprises: carry out the setting of this device as follows: determine and store the relevant allowed band of detector that a plurality of pulse shapes are given up parameter that for described at least one detector these parameters are relevant with desired characteristic radiation to be detected; Operate this device as follows to make to survey desired characteristic radiation: determine pulse shape parameter from the output signal of described at least one detector; With will compare from the pulse shape parameter allowed band relevant of the output signal of described at least one detector with the detector of described storage; Wherein, if not within the relevant allowed band of the detector of being stored, should be rejected outside the detection of desired characteristic radiation from output signal of described at least one detector from the pulse shape parameter of the output signal of described at least one detector.

45. according to the method for claim 44, wherein said setting comprises: the sample that described at least one detector is provided the radioactive source of desired characteristic radiation; Obtain a plurality of pulses from described at least one detector; Set up and store the histogram of these a plurality of pulses, comprise current basic line and in 1/4,1/2 and 3/4 locational pulse width of its pulse height; A plurality of pulse shapes of described at least one detector are given up parameter determine that the relevant allowed band of detector for for each histogram, is accepted 99% of this histogrammic adjacent main peak area; Storage is given up the relevant allowed band of the determined detector of parameter to a plurality of pulse shapes of described at least one detector.

46. according to the method for claim 45, the wherein said setting further comprises: obtain a plurality of coincident event, coincident event is the incident that the output from first and second detectors meets substantially; By set up histogram with utilize histogram method 99% accept that relevant main peak area is determined and the allowed band of storage pulse displacement parameter; Allowed band with the storage pulse displacement parameter.

47. method according to claim 46, the wherein said setting further comprises: set up three independently relevant with desired characteristic radiation energy spectrums, the power spectrum that comprises first detector, the power spectrum of second detector and the bidimensional power spectrum of a coincident event.

48. method according to claim 44, wherein, when this device of operation is surveyed desired characteristic radiation, determine to comprise: on the time window of one period short time before the whole width that covers this pulse and pulse are risen a plurality of data points are obtained in each received pulse from the pulse shape parameter of the output signal of described at least one detector; Calculate the mean value of several data points of foremost and determine current basic line; If the current basic line of being calculated is different from zero significantly, give up this because pile up effect causes the pulse of distortion; If pulse is not rejected in previous step, scans ensuing a plurality of data point and find out a maximal value; Surpass an overflow value if find maximal value, give up to fall this pulse; If pulse is not rejected in each step in front, the peak position amplitude of calculating this pulse is the difference between described maximal value and the current basic line; Begin to scan forward and backward to determine the time offset on the amplification level of a plurality of minutes several times of this peak position amplitude from the peak position of described pulse; At least use the pulse shape parameter of determined time offset conduct from the output signal of described at least one detector.

49. method according to claim 48, wherein, when this device of operation is surveyed desired characteristic radiation, relatively the comprising of the allowed band that the pulse shape parameter of output signal is relevant with the detector of storage: determine whether on 1/2,1/4 and 3/4 times amplification level of the peak position amplitude of pulse time offset drops in the allowed band that the detector of described storage is correlated with.

50. method according to claim 48, wherein said at least one detector comprises one first detector and one second detector, the wherein said setting further comprises: obtain a plurality of coincident event, a coincident event is meant that the output signal from first and second detectors meets substantially; By setting up histogram and utilizing 99% the adjacent main peak area of accepting of histogram method to determine allowed band with the storage pulse displacement parameter; Allowed band with the described pulse displacement parameter of storage; Wherein operate this device and survey desired characteristic radiation and further comprise the generation that test meets in operation, comprising: determine from the distance between the time offset separately on 1/4 amplification level on the rising front of the pulse separately of first and second detectors; With determined distance is compared with the allowed band of the pulse displacement parameter of described storage.

51., further comprise for concrete this device of isotope scale according to the method for claim 44.

52. one kind manufactures a product, and comprises a computer-readable storage medium, this storage medium has a physique to express the computer program substrate, and this computer program comprises the unit that is used for being provided with and operating programmable particle/Radiation Emission sniffer.

53. be used for the detector assembly of gamma-rays and X-radiation, comprise: scintillator crystals, the photomultiplier that is connected with this scintillator crystals optics, the photomultiplier transit pedestal tube electronic circuit module of the one that is connected with this photomultiplier, comprise a high-voltage power supply, voltage divider and amplifier, between this base module and this photomultiplier, between this photomultiplier and this scintillator crystals, around photomultiplier with around a plurality of shields of scintillator-photomultiplier-base module assembly, use all material in this detector to have radioactivity below about 1cpm background.

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