CN104749086B - More reference channel pulse recognition method, apparatus and particle analyzer - Google Patents
More reference channel pulse recognition method, apparatus and particle analyzer Download PDFInfo
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Abstract
本申请公开了一种多参考通道脉冲识别方法和装置、粒子分析仪，识别方法包括：对于发现脉冲的单参考通道，基于发现的待识别脉冲确定该单参考通道的待处理数据中的无效数据区；根据各单参考通道的无效数据区统一多个参考通道的无效数据区的起止时间；基于统一起止时间后的无效数据区确定多个参考通道的有效数据区；在进行脉冲识别时对有效数据区的脉冲进行脉冲识别，对无效数据区的脉冲不再进行脉冲识别。本申请通过在多个参考通道之间确定起止时间统一的无效数据区的方式，将无法或者很难得出正确的面积、幅值和宽度信息的数据排除，不对其进行脉冲识别，从而减少了脉冲识别时的数据处理量。
The present application discloses a multi-reference channel pulse identification method and device, and a particle analyzer. The identification method includes: for a single reference channel where a pulse is found, determining invalid data in the pending data of the single reference channel based on the found pulse to be identified Unify the start and end time of the invalid data area of multiple reference channels according to the invalid data area of each single reference channel; determine the valid data area of multiple reference channels based on the invalid data area after the unified start and end time; The pulses in the valid data area are pulse identified, and the pulses in the invalid data area are no longer pulse identified. In this application, by determining the invalid data area with uniform start and end times among multiple reference channels, the data that cannot or is difficult to obtain the correct area, amplitude and width information is excluded, and the pulse identification is not performed on them, thereby reducing the number of pulses The amount of data processing at the time of recognition.
Description
Technical field
This application involves more reference channel pulse recognition sides in a kind of Medical Instruments more particularly to a kind of cytoanalyze
Method and device.
Background technique
Stream type cell analyzer is that one kind is used to analyze cell or molecule (is referred to as particle, below by taking cell as an example
Be illustrated) physicochemical characteristic instrument, principle makes sample as shown in Figure 1, flow cytometer generally uses sheath Flow Technique
Cell in this flows through flow chamber 1 by sheath fluid package sequence, and exciting light 2 is radiated at one by one on cell 3, and cell 3 is made to generate scattering
Light or fluorescence signal, treated circuit 6 forms electric pulse after handling after the conversion of photoelectric converter 5 after optical signal is collected
Signal 4 obtains its amplitude (H), area (A), width after carrying out pulse recognition to this pulse signal by pulse recognition module 7
(W) etc. it after parameters, shows finally by patterned mode, is analyzed for user.These scattering light or fluorescence signal
The parameters such as H, A, W, can reflect the expression of size, granularity and antigen molecule, content of intracellular inhereditary material of cell etc.,
And then from clinical medicine or biology angle, valuable reference information is obtained.Therefore various be excited carefully is correctly identified
Born of the same parents form the parameters such as amplitude, area, the width of pulse signal and are of great significance.
In the sample of measurement after each cell is excited, forward scattering light generally may can be all generated there are many cell
(FSC) and side scattered light (SSC), but whether fluorescence channel has signal, then according to the fluorescein on cell characteristic and cell
Whether there is or not be divided into following several situations: do not have, only all the way, have multichannel fluorescence signal.This cell is analyzed to generate in different channels
The information such as H, A, W of signal, it can be deduced that some characteristic informations about this cell.Due to that may contain in sample, there are many thin
Born of the same parents, and user is only interested in certain specific cells, and threshold at this moment is arranged often through in some channel (referred to as " reference channel ")
Value, so that the pulse that peak value is less than threshold value in the channel is ignored, the pulse greater than threshold value is collected and then analysis obtains H, A, W
Etc. information, analysis show that the process of the information such as H, A, W of pulse is known as pulse recognition.
In some cases, user is interested in the signal in certain channels, then these channels is set as reference channel, more
Threshold value is set in a " reference channel ", logic ("AND" "or") fortune then is combined to the threshold decision result in these channels
It calculates, is judged whether to analyze this cell and provide the information such as H, A, W according to the result obtained.
Summary of the invention
The application provides more reference channel pulse recognition method and apparatus in a kind of cytoanalyze, reduces mostly with reference to logical
Data operation quantity in road pulse identification process.
According to a first aspect of the present application, the application provides a kind of more reference channel pulse recognition methods, comprising:
The signal for acquiring multiple reference channel outputs obtains the pending data of each reference channel, the reference channel output
Signal be electric signal that the optical information issued after being optically excited by the tested particle that reference channel is collected is converted into；
Pending data and characteristic threshold value corresponding with the reference channel based on each single reference channel judge whether to find
Pulse, the characteristic threshold value are the threshold value of the feature of interest of particle of interest, and the discovery pulse, which refers to, detects pulse peak
Value is greater than the pulse of characteristic threshold value；
For finding single reference channel of pulse, the to be processed of the list reference channel is determined based on the pulse to be identified of discovery
Invalid data area in data；
According to the beginning and ending time in the invalid data area of the unified multiple reference channels in invalid data area of each single reference channel；
The valid data area of multiple reference channels is determined based on the invalid data area after the unified beginning and ending time；
Pulse recognition is carried out to the pulse in valid data area when carrying out pulse recognition, no longer to the pulse in invalid data area
Carry out pulse recognition.
According to a second aspect of the present application, the application provides a kind of more reference channel pulse recognition devices, comprising:
Data acquisition unit, the signal for acquiring multiple reference channel outputs obtain the number to be processed of each reference channel
According to the signal of the reference channel output is the optical information conversion issued after being optically excited by the tested particle that reference channel is collected
At electric signal；
Pulse finds unit, for pending data and feature corresponding with the reference channel based on each single reference channel
Whether threshold decision finds pulse, and the characteristic threshold value is the threshold value of the feature of interest of particle of interest, the discovery pulse
Refer to the pulse for detecting that peak value of pulse is greater than characteristic threshold value；
Single channel dead space determination unit, for single reference channel for finding pulse, the arteries and veins to be identified based on discovery
Rush the invalid data area in the pending data for determining the list reference channel；
Dead space Unified Element, for unifying the invalid of multiple reference channels according to the invalid data area of each single reference channel
The beginning and ending time of data field；
Effective district determination unit determines the significant figure of multiple reference channels based on the invalid data area after the unified beginning and ending time
According to area；
Pulse recognition unit, for carrying out pulse recognition to the pulse in valid data area when carrying out pulse recognition, to nothing
The pulse of effect data field no longer carries out pulse recognition.
According to the third aspect of the application, the application provides a kind of particle analyzer, comprising:
Excitation light source, for providing the exciting light for irradiating tested particle；
Flow chamber, for providing tested particle illuminated place；
Light collecting device, for collecting the optical information issued after tested particle is optically excited, the light collecting device includes
Multiple reference channels；With
Above-mentioned more reference channel pulse recognition devices.
The application will be unable to by way of determining beginning and ending time unified invalid data area between multiple reference channels
Or it is difficult to obtain that the data of correct area, amplitude and width information exclude, pulse recognition is not carried out to it, to reduce
Data processing amount when pulse recognition.
Detailed description of the invention
Fig. 1 is flow cytometer working principle diagram；
Fig. 2 is the structural schematic diagram of flow cytometer；
Fig. 3 is a kind of structural schematic diagram of the multichannel pulse recognition device of embodiment of the application；
Fig. 4 is pulse shape signature analysis figure；
Fig. 5 is a kind of flow chart of more reference channel pulse recognitions of embodiment of the application；
Fig. 6 is the flow chart for determining invalid data area in a kind of embodiment for single reference channel；
Fig. 7 is the flow chart of the beginning and ending time in the invalid data area of unified multiple reference channels in embodiment a kind of；
Fig. 8 is longitudinal one of schematic diagram for polluting and laterally polluting；
Fig. 9 is the two of longitudinal schematic diagram for polluting and laterally polluting；
Figure 10 is a kind of a kind of structural schematic diagram of the effective district determination unit of embodiment of the application；
Figure 11 is a kind of another structural schematic diagram of the effective district determination unit of embodiment of the application；
Figure 12 is the flow chart that a kind of effective district of embodiment of the application determines；
Figure 13 is the schematic diagram that invalid data area is determined according to similitude rule；
Figure 14 is that pulse window is overlapped schematic diagram in a kind of embodiment of the application.
Specific embodiment
Below by specific embodiment combination attached drawing, invention is further described in detail.
Flow cytometer be a kind of particle analyzer, the embodiment of the present application using flow cytometer to particle carry out detection and
Analysis, the structure of flow cytometer is as shown in Fig. 2, include excitation light source 1025, flow chamber 1022, light collecting device and processor
1026, excitation light source 1025 is used to provide the exciting light for irradiating tested particle, such as laser；Flow chamber 1022 is tested for providing
The illuminated place 1021 of particle；Light collecting device is for collecting the optical information issued after tested particle is optically excited comprising
All reference channels and non-reference channel；Each channel includes optical module 1023 and electrooptical device 1024, optics group
Part 1023 turns for completing scattering light or collection, the shaping of fluorescence etc., the optical information that electrooptical device 1024 is used to collect
It is changed to electric signal and is output to processor 1026, processor 1026 is for handling electric signal.
In order to illustrate analytic process, the term used in the application is explained.
Reference channel and non-reference channel: as shown in Figure 1, a particle can generate pulse signal in multiple channels.For
For some particle of interest, if user is in n(n >=2) feature of interest with the particle of interest is provided on a channel
This n channel is then referred to as " reference channel " by relevant characteristic threshold value, and remaining channel is referred to as " non-reference channel ".Such as
User is provided with characteristic threshold value relevant to the feature of interest of the particle of interest in each channel, then channel is entirely
Reference channel, without non-reference channel.
It was found that pulse: user is in the feature of interest phase that the characteristic threshold value that reference channel is arranged is one with particle of interest
The reference point of pass is thought to find a pulse, thus triggering is known if having found the data greater than the reference point in the channel
Other process.If not finding the data greater than the reference point, then it is assumed that do not find pulse.May have in reference channel very much
" small-pulse effect ", but since it is not more than threshold value set by user, so will not be found.
Invalid data area: the purpose of pulse recognition is the information such as A, H, the W that calculate pulse existing for each channel.Such as
The data of fruit some regions can not or be difficult to obtain correct A, H, W information, then facilitating to handle by this part
Data are set as invalid data, do not carry out discriminance analysis to it.This segment data area is exactly " invalid data area "；The purpose done so
It is to keep the Project Realization of algorithm more simple and feasible.
Valid data area: corresponding with invalid data area, the data for needing to participate in pulse recognition are valid data, the number of segment
It is exactly " valid data area " according to area.
Laterally pollution and longitudinal pollution: since certain section " invalid data area " leads to another part data according to certain rule
Also become " invalid data area ", then claim the latter by " pollution "；Laterally pollution refers to the pollution carried out in same reference channel,
Longitudinal pollution refers to the pollution carried out between multiple reference channels.
Pulse combined: the same particle has certain similitude, such as width phase in the pulse that multiple interchannels are formed
Closely, peak value moment is close, corresponds etc., and it is same effective for being corresponded the pulse of different reference channels using the similitude
The process for the pulse that particle issues is known as pulse combined.
In the embodiment of the present application, the invalid data area with the unified beginning and ending time is determined in reference channel first, into
And determine valid data area, pulse recognition processing only is carried out to the data in valid data area when carrying out pulse recognition, thus
Reduce the data processing amount during pulse recognition, and because having abandoned some data that can not be obtained a result, to also mention
The high accuracy of all kinds of results after pulse recognition.
Embodiment one:
Processor 1026 in Fig. 2 includes multichannel pulse recognition device, for the multichannel to input processor 1026
Electric signal carries out pulse recognition, as shown in figure 3, multichannel pulse recognition device 30 includes data acquisition unit 31, pulse discovery
Unit 32, single channel dead space determination unit 33, dead space Unified Element 34, effective district determination unit 35 and pulse recognition unit
36。
The signal that data acquisition unit 31 is used to acquire multiple reference channel outputs obtains the number to be processed of each reference channel
According to the signal of reference channel output is that the optical information issued after being optically excited by the tested particle that reference channel is collected is converted into
Electric signal.
Pulse finds that unit 32 is used for pending data and spy corresponding with the reference channel based on each single reference channel
Whether sign threshold decision finds pulse, and characteristic threshold value is the threshold value of the feature of interest of particle of interest, and discovery pulse refers to inspection
Measure the pulse that peak value of pulse is greater than characteristic threshold value.As shown in figure 4, the output waveform after processing of circuit is in no particle
The baseline voltage 41 that a direct current is maintained when luminous when having particle to pass through and producing scattered light signal, then generates an arteries and veins
Rush signal.When the pulse amplitude (part more than baseline) is more than set characteristic threshold value 42, then it is assumed that find an arteries and veins
Punching.Pulse area between former and later two of pulse and characteristic threshold value intersection point (i.e. threshold point) is known as threshold window 43, front and back threshold value
Point respectively forwardly, extend one section of region backward, form preceding expanded window 44 and rear expanded window 45, front and back expanded window 44 45 and threshold value
Pulse window 46 is collectively formed in window 43.The spreading range of front and back expanded window, according to the feature of test object and user's use habit come
It determines, the range after in general guaranteeing extension can cover entire impulse waveform range.
Single channel dead space determination unit 33 is used for single reference channel for finding pulse, the arteries and veins to be identified based on discovery
Rush the invalid data area in the pending data for determining the list reference channel.If it find that the pulse window of the pulse in identification process
Have with the pulse window of front and back pulse overlapping, then it is assumed that these pulses are idler Pulse, and the discarding of this segment data does not use.In addition
When the width for finding this pulse is excessively wide or excessively narrow, also it is thought that a spurious pulse, is considered as idler Pulse.Invalid arteries and veins
Rushing the period that window is related to is confirmed as invalid data area.Therefore, in a kind of specific example, single channel dead space determination unit
33 include that pulse window determines that subelement, the first judgment sub-unit and the second judgment sub-unit, pulse window determine that subelement is used for really
The pulse window of fixed pulse to be identified, pulse window are the region that pulse continues；First judgment sub-unit, it is current to be identified for judging
Whether the pulse window of the pulse window of the pulse to be identified pulse adjacent with its front and back is be overlapped, if it is, will be related to the arteries and veins of overlapping
Window region is rushed as invalid data area；Second judgment sub-unit is used to judge whether the pulse width of pulse to be identified to be abnormal, such as
Fruit is, then using the pulse window region of the pulse to be identified of the exception as invalid data area.
Dead space Unified Element 34 is used for the nothing of the unified multiple reference channels in invalid data area according to each single reference channel
Imitate the beginning and ending time of data field.In a specific example, dead space Unified Element includes longitudinal pollution subelement, laterally pollution
Unit and third judgment sub-unit.Longitudinal pollution subelement is used for one by one using single reference channel with invalid data area as quilt
Than reference channel compared with other reference channels, the pending data region of other reference channels is neutralized by than reference channel
The beginning and ending time in the invalid data area identical period is as invalid data area；Laterally pollution subelement is for judging each single reference
Whether the pulse window that the invalid data area in channel is adjacent with front and back has overlapping, if so, being then related to the pulse window region of overlapping
As invalid data area；Third judgment sub-unit is used to judge whether the invalid data area of each single reference channel to have unified rise
The only time determines according to judging result by longitudinally polluting subelement and laterally pollution subelement works on or end loop.
Effective district determination unit 35 determines the effective of multiple reference channels based on the invalid data area after the unified beginning and ending time
Data field, for example, by the data field in entire data field in addition to invalid data area be valid data area.
Pulse recognition unit 36 is for carrying out pulse recognition to the pulse in valid data area when carrying out pulse recognition, to nothing
The pulse of effect data field no longer carries out pulse recognition.
More reference channel pulse recognition devices based on the present embodiment, when the pulse to multichannel identifies, place
Process is managed as shown in figure 5, including following below scheme:
Step 50, the signal for acquiring multiple channel outputs obtains the pending data in each channel, the signal of each channel output
The electric signal that the optical information that tested particle to be collected by each channel issues after being optically excited is converted into.Multiple channels scatter light
Signal or fluorescence signal are collected by each channel, are formd after photoelectric conversion, signal processing circuit processing are carried out in each channel
Analog signal continuous in time carries out sample conversion to this signal using the AD device with certain sample rate, simulation is believed
Number become discrete digital signal.Sampling has obtained the digital quantity of analog voltage signal at that time, such each sampled point every time
Referred to herein simply as " point ".Since the sampling of AD device converts, continuous analog signal is become into a series of digital quantity
" point ", since " point " is very intensive, after connecting can basic restoration simulation signal waveform.The subsequent described waveform number of the application
According to, all refer to by AD turn after digital data.Mode subsequently through software or logic circuit divides Wave data
Analysis processing.
Step 51, pending data and characteristic threshold value corresponding with reference channel judgement based on each single reference channel are
No discovery pulse, the characteristic threshold value are the threshold value of the feature of interest of particle of interest.In the present embodiment, in multiple channels
At least be arranged two reference channels, handled first against the Wave data of reference channel, judge it is each list reference channel in be
It is no to be found pulse.As shown in figure 4, think to find a pulse when the peak value for detecting certain pulse is greater than characteristic threshold value, it should
Pulse is known as pulse to be identified.If the peak value of pulse is less than or equal to characteristic threshold value, the pulse is abandoned.
Step 52, for single reference channel of discovery pulse, which is determined based on the pulse to be identified of discovery
Pending data in invalid data area；If not knowing the list with reference to logical without discovery pulse in some reference channel
Whether road has invalid data field.When determining the invalid data area of single reference channel, if detect that pulse window has overlapping, or
Pulse width has exception, belongs to idler Pulse, and the period being related to is invalid data area.Specific process flow such as Fig. 6 institute
Show, comprising the following steps:
Step 60, the threshold window of pulse to be identified is detected based on characteristic threshold value, the threshold window is pulse to be identified and spy
Sign threshold value is formed by the pulse area between two threshold points of boundary intersection.
Step 61, threshold window respectively forwardly and after rear extension presumptive area is obtained into pulse window.Pulse window is pulse continuity
Region, in order to make pulse window be completely covered pulse continuity region, to prevent missing data, by threshold window respectively forwardly and after
Pulse window is obtained after extending scheduled one section of region, as shown in figure 4, threshold window 43 obtains preceding extension after extending presumptive area forward
Window 44 obtains rear expanded window 45 after extending presumptive area backward, and the period of pulse window 46 is equal to preceding expanded window 44 and adds threshold value
Window 43 adds rear expanded window 45.Extension have following effect: 1, extend after can in expanded window integral calculation pulse area；2,
By extension, it can guarantee in expanded window with difference of the pulse between redundant channel in generation time, calculate each channel
When area, it can guarantee to cover entire pulse.Front and back extension window width setting and characteristic threshold value be provided with it is certain
Relationship, if the closer pulse apex of characteristic threshold value setting, needs extension is bigger could cover entire pulse, threshold value more connects
Nearly bottom, then extension does not need to cover greatly very much.
Step 62, whether the pulse window of the pulse window of the current pulse to be identified of the judgement to be identified pulse adjacent with its front and back
Overlapping, if so, 63 are thened follow the steps, it is no to then follow the steps 64.
Step 63, the pulse window region of overlapping will be related to as invalid data area.It, can not be effective when pulse window has overlapping
The area or areal calculation inaccuracy for calculating the pulse will then be related to the front and back pulse of overlapping so if pulse window has overlapping
The period that window is covered as invalid data area, is not involved in subsequent pulse recognition.
Step 64, judge whether the pulse width of pulse to be identified is abnormal, if so, 63 are thened follow the steps, by the exception
Pulse to be identified pulse window region as invalid data area.It is no to then follow the steps 65, continue to test next pulse to be identified.
Under normal conditions, pulse corresponding to the light that tested particle generates after being excited has certain characteristic, even if by
Different channels are detected, and the pulse shape in each channel is also with uniformity, and generation time is identical.It therefore, can be according to this kind
The pulse shape that particle generates is tested to judge whether pulse is that effective particle generates.In the present embodiment, using pulse width
Reflect pulse shape, for example, can using half-peak breadth (pulse width i.e. at peak value half) or equivalent width as pulse width,
When how small pulse width is excessive or, it is believed that pulse shape is not met, then the pulse is likely to interference signal, therefore pulse
The pulse of width exception is considered as idler Pulse, and the period involved in pulse window is considered as invalid data area, is not joined
With subsequent pulse recognition.
Step 53, according to the start-stop in the invalid data area of the unified multiple reference channels in invalid data area of each single reference channel
Time.It, will be undesirable or can not obtain legitimate result by the beginning and ending time in the invalid data area of unified each reference channel
Data exclude, thus data processing amount when reducing pulse recognition.In a specific embodiment, unified by following steps
The beginning and ending time in the invalid data area of multiple reference channels, as shown in Figure 7.
Step 70, longitudinal pollution step.One by one using single reference channel with invalid data area as by than reference channel
Compared with other reference channels, the pending data region of other reference channels is neutralized by the invalid data area than reference channel
The beginning and ending time identical period as invalid data area.The invalid data area of multiple reference channels has phase after longitudinal pollution
With at the beginning of and the end time.
Step 71, step is laterally polluted.The invalid data area of each single reference channel is adjacent with front and back after the longitudinal pollution of judgement
Pulse window whether have overlapping, if so, be then related to overlapping pulse window region be also used as invalid data area.Each reference channel
It is interior, since data buffer area is limited, legacy data to be removed is carried out with identification, increases new data.Therefore preferably implementing
In example, only retain the low volume data before the pulse recognition moment, the size of data volume can guarantee Chong Die with current PRF previous
Pulse data can be found in buffer area, but it cannot be guaranteed that more data can also be found before this.So having with invalid data area
The previous pulse window of overlapping only pollutes once, and later has the sustainable pollution of overlapping pulses window.That is: when have one piece of data area at
When for invalid data area, if then having weight with this section of invalid data earlier than the pulse window of its pulse generated on the time
Folded or contact, then this pulse window region is contaminated into invalid data area, and the two is linked together, and becomes invalid data area entirely, this section
If there are also pulse window, this pulse windows no longer to be polluted in data front, recognition result retains.If one section of invalid data
There is overlapping in area with the pulse window generated later or contacts, then the pulse window generated later is contaminated, and the two is linked together, if after
Side has pulse window to contact again, then three is linked together, and becomes invalid data area entirely, can be continued for pollution and go down, this claims
For chronic pollution.The beginning and ending time for executing the invalid data area of each reference channel after laterally polluting may be different, therefore holds
Row step 72.
Step 72, judge whether the beginning and ending time in the invalid data area of multiple reference channels is consistent, if each reference channel
Invalid data area beginning and ending time it is identical, then otherwise end loop turns to and executes step 70.
So circulation, until detection after and all reference channels " invalid data area " all have it is identical at the beginning of
Between and the end time.Longitudinal pollution and laterally pollution as shown in figure 8, pulse window T1-T2 shown in solid in reference channel 2 and
Pulse window overlapping has occurred in pulse window T3-T4 shown in dotted line, leads to the pulse window region of all coherent pulses in channel 2 (i.e.
The region T1-T4 in figure) data invalid, according to longitudinal pollution, in the same time period in channel 1 data field (T1-T4) also without
Effect, then further according to lateral pollution, the pulse window region T5-T6 in channel 1 also becomes invalid data, then further according to longitudinal dirt
Dye, (channel 1 and channel 2 i.e. as shown in the figure) region T1-T6 of all reference channels become invalid data area.For another example Fig. 9 institute
Show, the pulse width in channel 1 is abnormal, and pulse is wide, and pulse window T3-T4 becomes invalid data area, according to longitudinal pollution, channel 2
The region T3-T4 also become invalid data area, and since the region T3-T4 in channel 2 is Chong Die with pulse window T1-T2, according to transverse direction
Pollution causes pulse window T1-T2 to become invalid data area and eventually leads to the T1-T4 of all reference channels further according to longitudinal pollution
Region becomes invalid data area.
Step 54, the valid data area of multiple reference channels is determined based on the invalid data area after the unified beginning and ending time.Have
Effect data field can be entire data field and exclude the data field behind invalid data area, can also determine significant figure by other means
According to area.Valid data area should not be overlapped with invalid data area.
Step 55, whether find that pulse determines the logical value of each reference channel according to each reference channel.Each with reference to logical
In road, according to " it was found that pulse is then 1 ", the rule of " not finding that pulse is then 0 ", in each reference channel by its pulse validity
Chx_Valid is assigned a value of " 1 " or " 0 ".
Step 56, logical value and logical algorithm based on each reference channel carry out logical operation.It can in UI operation interface
"or" logical operation is still done to select multiple channels to do "AND" logical operation, based on different situations, user may be different
Selection, according to the user's choice, the Chx_Valid of each reference channel is carried out logical operation, and to obtain more reference channels final
Validity result ChAll_Valid.
Step 57, determined whether to carry out pulse recognition to the pending data in all channels according to logic operation result, such as
Fruit is to then follow the steps 58, no to then follow the steps 59.For example, if final result ChAll_Valid is " 0 ", all channels
Valid data area be also configured as " invalid data area ", no longer progress pulse recognition.If final result ChAll_Valid is
" 1 ", then continue to execute step 58.
Step 58, pulse recognition is carried out to the pending data in all channels, when carrying out pulse recognition only to significant figure
Pulse recognition is carried out according to the pulse in area, pulse recognition is no longer carried out to the pulse in invalid data area.It is calculated when pulse recognition effective
A, H, W information of the pulse of data field simultaneously export.
Step 59, terminate.
After the present embodiment is polluted by vertical and horizontal, corresponding to all width are abnormal, pulse window overlapping pulse
Pulse window region is removed, that is, the region that would be impossible to effectively be calculated is set to invalid data area, is carrying out pulse recognition
When, pulse recognition operation is not carried out to invalid data area, to reduce data operation quantity.Due to the pulse in invalid data area
The usually disturbing pulse either pulse that can not effectively be calculated, therefore remove after these pulses while also improving calculating
As a result accuracy.
Embodiment two:
According to above-described embodiment, after determining invalid data area, valid data area is further determined that, when subsequent identification pulse
Pulse recognition operation is carried out only for the data in valid data area.The difference of the present embodiment and above-described embodiment is the provision of one
The preferable valid data area of kind determines scheme.
In the present embodiment, effective district determination unit is used for according to same particle between the pulse that multiple reference channels are formed
Similitude rule, by carrying out pulse combined to data area of multiple reference channels in addition to the invalid data area, in pulse
It will be seen that single reference channel of pulse is used as by than reference channel when combination one by one, invalid data area will be removed than reference channel
Pulse window in outer data area is used as by than time zone.Having for multiple reference channels is determined according to pulse combined result
Data field is imitated, valid data area includes at least the successful pulse window region of pulse combined.
In a kind of specific example, as shown in Figure 10, similitude rule includes: in the respective pulses window of multiple reference channels
Pulse be no more than 1.Effective district determination unit 351 include threshold point obtain subelement 3510, the 4th judgment sub-unit 3511,
5th judgment sub-unit 3512 and the 6th judgment sub-unit 3513.Threshold point obtains subelement 3510 for obtaining other each references
Channel by than the threshold point in time zone；4th judgment sub-unit 3511 be used to judge other reference channels it is single by than when
Between the quantity of threshold point in region (i.e. individually by than time zone) whether be equal to 0, if the quantity of threshold point is equal to 0,
Illustrate the reference channel this by than no pulse in time zone, threshold point it is in varying numbers in 0, then the quantity of threshold point may
It is 1,2,3 even more.Directly think this by than the pulse combined success in time zone when the quantity of threshold point is equal to 0;
5th judgment sub-unit 3512 is used to judge single quilt in the in varying numbers in 0 when of 3511 judgment threshold point of the 4th judgment sub-unit
Whether the quantity than the threshold point in time zone is equal to 2.If be equal to 2, illustrate the reference channel this by than time zone
It may only one pulse in domain.If be not equal to 2, illustrate the reference channel this by more more than one than having in time zone
Pulse, such as 1.5 or 2, then think that this is failed than the pulse combined in time zone in this case；6th judgement
Subelement 3513 is used to sentence when the 5th judgment sub-unit 3512 judges that list is equal to 2 by the quantity than the threshold point in time zone
The time of preceding threshold point in two threshold points of breaking whether prior to rear threshold point time, if it is, illustrating that the reference is logical
This of road is by than only one pulse in time zone, it is believed that and this is succeeded than the pulse combined in time zone, otherwise it is assumed that
This is failed than the pulse combined in time zone, and this of the reference channel is by than may be previous pulse in time zone
The previous section of aft section and the latter pulse.
In another specific example, as shown in figure 11, similitude rule includes: the respective pulses window of multiple reference channels
Interior pulse is no more than 1 and peak value moment is close.Effective district determination unit 352 includes that threshold point obtains subelement 3520, the
Four judgment sub-units 3521, the 5th judgment sub-unit 3522, the 6th judgment sub-unit 3523 and the 7th judgment sub-unit 3524.Threshold
Value point obtain subelement 3520 be used for obtain other each reference channels by than the threshold point in time zone；4th judgement is single
Member 3521 is used to judge whether the single of other reference channels to be equal to 0 by the quantity than the threshold point in time zone, if it is,
Think this by than the pulse combined success in time zone;5th judgment sub-unit 3522 is single by than in time zone for judging
The quantity of threshold point whether be equal to 2, if being not equal to 2, then it is assumed that this is failed than the pulse combined in time zone；6th
Judgment sub-unit 3523 is used to sentence when the 5th judgment sub-unit judgement list is equal to 2 by the quantity than the threshold point in time zone
The time of preceding threshold point in two threshold points of breaking whether prior to rear threshold point time, if the time of preceding threshold point is later than
The time of threshold point afterwards, then it is assumed that this is failed than the pulse combined in time zone；7th judgment sub-unit 3524 is used for
When 6th judgment sub-unit judges the time of time of preceding threshold point prior to rear threshold point, the same quilt of all reference channels is judged
Whether it is greater than interval threshold than the difference between the peak value of pulse moment in time zone, if it is, thinking this by than the time
Pulse combined failure in region, otherwise it is assumed that this is by than the pulse combined success in time zone.
Since the same particle has certain similitude, such as similar width, peak in the pulse that multiple interchannels are formed
It is worth the moment is close, corresponds (particle can not form 2 or more pulses in a channel, can only be 0 or 1 pulse) etc.,
If it find that the pulse between reference channel does not meet these features, then it is assumed that this is not an effective particle signal.Based on this
The effective district determination unit of embodiment determines valid data area using the pulse similitude rule of same particle synchronization,
A kind of process of preferable specific embodiment is as shown in figure 12, comprising the following steps:
Step 120, it will be seen that single reference channel of pulse is used as by than reference channel one by one, it will be by removing than reference channel
It goes to the data area outside the invalid data area determined using the scheme of embodiment one to be known as initial valid data area, will initially have
Imitate each pulse window in area as one than time zone, obtained other each reference channels by than the threshold value in time zone
Point.
Step 121, judge whether the single of other reference channels is equal to 0 by the quantity than the threshold point in time zone, such as
Fruit is, then it is assumed that this is no to then follow the steps 122 by than the pulse combined success in time zone.
Step 122, judge whether list is equal to 2 by the quantity than the threshold point in time zone, if being not equal to 2, recognize
Failed for this than the pulse combined in time zone, if being equal to 2, executes following steps；
Step 123, after judging whether list is later than by the time than the preceding threshold point in two threshold points in time zone
Otherwise the time of threshold point executes following steps if it is, thinking that this is failed than the pulse combined in time zone；
Step 124, judge the same by than the difference between the peak value of pulse moment in time zone of all reference channels
Whether be greater than interval threshold, if it is, think this by than in time zone pulse combined fail, otherwise it is assumed that this by than when
Between pulse combined success in region.
Can be using the successful pulse window region of pulse combined as valid data area, valid data area is pulse combined success
All respective pulses windows time zone superposition.The region of pulse combined failure can also be considered invalid data area,
Invalid data area newly determining in the present embodiment is removed in initial valid data area again, it is remaining for for pulse recognition operation
Valid data area.Such as:
The above judgment step is refined as within the pulse window period of any one reference channel to other reference channels
It is identified, judges following several points:
A) only one threshold point of the pulse of other reference channels, such as situation P2 corresponding in channel 1 in Figure 13；
B) there are 3 or more threshold points for the pulse of other reference channels, such as situation P1 corresponding in channel 1 in Figure 13；
Although c) there are two threshold points, its " preceding threshold point " time to be later than " rear threshold value for other reference channel pulses
Point ", such as situation P3 corresponding in channel 1 in Figure 13；
If it find that any one of three cases above, then it is invalid to be determined according to " laterally pollution " and " longitudinal pollution "
Data field.If happened without any one of three cases above, that is, the pulse window of any one reference channel
In period, other reference channels all only have the normal front and back threshold point of 2 sequences (rear threshold value point moment > before threshold value point moment)
Or 0 threshold point, then it further includes steps of
All pulse windows in the valid data area of each reference channel are overlapped.Since a particle generates in multiple channels
Pulse inevitably has small difference, and the pulse window on multiple channels is at state pause judgments moment time although the moment is close
Inevitably there is a difference, in the present embodiment by way of taking " union ", obtains in all pulse windows earliest moment T1 and the latest moment
T2 forms the new period, and as shown in figure 14, which covers all pulses in the valid data area of all reference channels
Window, that is, " overlapping ".
By the peak value moment of the pulse between multiple reference channels (when being considered as peak value at the time of can corresponding to the midpoint of threshold window
Carve) it is compared, if (a value shown in Figure 14, a value can be set the big Mr. Yu's value of the maximum deviation of peak value according to the actual situation
It is fixed), then all coherent pulse windows region is " invalid data area " all in accordance with " laterally polluting " and " longitudinal to pollute " rule settings.
After determining valid data area, in the valid data area T1-T2 period shown in Figure 14, each with reference to logical
In road, according to " it was found that pulse is then the rule of 1, " not finding that pulse is then 0 ", in each reference channel by its pulse validity
Chx_Valid is assigned a value of " 1 " or " 0 ", according to the "AND" of user setting/inclusive-OR operation rule, by the Chx_ of each reference channel
Valid carries out logical operation and obtains the final validity result ChAll_Valid of more reference channels.If final result ChAll_
Valid is " 0 ", then the data in all channels between T1-T2 are set as " invalid data area ", otherwise further identification.
If ChAll_Valid is " 1 ", all reference channels, non-ginseng are identified in the T1-T2 period shown in Figure 14
It examines A, H, W information in channel and exports.Conventional method is: maximum value is scanned in the T1-T2 period shown in Figure 14 as arteries and veins
Rush peak value H, the W of the integral result that all the points the are added A as pulse, A divided by the result of H as pulse.In this way, final
A, H, W information in all channels are identified.
The present embodiment is after determining invalid data area, in initial valid data area further again using similitude rule
It determines the corresponding valid data area of effective impulse that same particle generates, further eliminates and some need not participate in pulse knowledge
Other data, to further reduce data operation quantity and improve the accuracy of calculated result.
It will be understood by those skilled in the art that all or part of the steps of various methods can pass through in above embodiment
Program instructs related hardware to complete, which can be stored in a computer readable storage medium, storage medium can wrap
It includes: read-only memory, random access memory, disk or CD etc..
The above content is specific embodiment is combined, further detailed description of the invention, and it cannot be said that this hair
Bright specific implementation is only limited to these instructions.For those of ordinary skill in the art to which the present invention belongs, it is not taking off
Under the premise of from present inventive concept, a number of simple deductions or replacements can also be made.
Claims (21)
- The pulse recognition method of reference channel more than 1., it is characterised in that include:The signal for acquiring multiple reference channel outputs obtains the pending data of each reference channel, the letter of the reference channel output Number electric signal being converted into for the optical information issued after being optically excited by the tested particle that reference channel is collected；Pending data and characteristic threshold value corresponding with the reference channel based on each single reference channel judge whether discovery pulse, The characteristic threshold value is the threshold value of the feature of interest of particle of interest, and the discovery pulse, which refers to, detects that peak value of pulse is greater than The pulse of characteristic threshold value；For finding single reference channel of pulse, the pending data of the list reference channel is determined based on the pulse to be identified of discovery In invalid data area；According to the beginning and ending time in the invalid data area of the unified multiple reference channels in invalid data area of each single reference channel；The valid data area of multiple reference channels is determined based on the invalid data area after the unified beginning and ending time；Pulse recognition is carried out to the pulse in valid data area when carrying out pulse recognition, the pulse in invalid data area is no longer carried out Pulse recognition.
- 2. the method as described in claim 1, which is characterized in that the pulse to be identified based on discovery determines the list with reference to logical Invalid data area in the pending data in road includes:Determine that the pulse window of pulse to be identified, the pulse window are the region that pulse continues；Judge whether the pulse window of the pulse window of the current pulse to be identified to be identified pulse adjacent with its front and back is be overlapped, if It is that will then be related to the pulse window region of overlapping as invalid data area；Judge whether the pulse width of pulse to be identified is abnormal, if it is, by the pulse window area of the pulse to be identified of the exception Domain is as invalid data area.
- 3. method according to claim 2, which is characterized in that the pulse window of the determination pulse to be identified includes:The threshold window of pulse to be identified is detected based on characteristic threshold value, the threshold window is formed by pulse to be identified with characteristic threshold value Boundary intersection two threshold points between pulse area；Threshold window respectively forwardly and after rear extension presumptive area is obtained into pulse window.
- 4. method according to claim 2, which is characterized in that according to the unified multiple ginsengs in invalid data area of each single reference channel The beginning and ending time for examining the invalid data area in channel includes:Circulation executes following steps, until the invalid data area of each single reference channel has the unified beginning and ending time:Longitudinal pollution step, one by one using single reference channel with invalid data area as by more logical than reference channel and other references Road compares, and the pending data region of other reference channels is neutralized by the beginning and ending time phase in the invalid data area than reference channel The same period is as invalid data area；Laterally pollution step, judges whether the invalid data area of each single reference channel pulse window adjacent with front and back has overlapping, such as Fruit has, then the pulse window region for being related to overlapping is also used as invalid data area.
- 5. method according to any one of claims 1 to 4, which is characterized in that based on the invalid number after the unified beginning and ending time The valid data area for determining multiple reference channels according to area includes:According to similitude rule of the same particle between the pulse that multiple reference channels are formed, nothing is removed to multiple reference channels The data area imitated outside data field carries out pulse combined, determines the valid data area of multiple reference channels, the valid data Area includes at least the successful pulse window region of pulse combined.
- 6. method as claimed in claim 5, which is characterized in that the similitude rule includes: the correspondence of multiple reference channels Pulse in pulse window is no more than 1, and the pulse combined step includes:Will be seen that single reference channel of pulse is used as by than reference channel one by one, by by than reference channel in addition to invalid data area Data area in pulse window be used as than time zone, obtained other each reference channels by than the threshold value in time zone Point；Judge whether the single of other reference channels is equal to 0 by the quantity than the threshold point in time zone, if it is, thinking this By than the pulse combined success in time zone, following steps are otherwise executed；Judge whether list is equal to 2 by the quantity than the threshold point in time zone, if being not equal to 2, then it is assumed that this is by than the time Pulse combined failure in region executes following steps if being equal to 2；Judge it is single by the time than the preceding threshold point in two threshold points in time zone whether prior to rear threshold point time, If it is, thinking that this is succeeded than the pulse combined in time zone, otherwise it is assumed that this is by than the pulse group in time zone Close failure.
- 7. method as claimed in claim 5, which is characterized in that the similitude rule includes: the correspondence of multiple reference channels Pulse in pulse window is no more than 1 and peak value moment is close, and the pulse combined step includes:Will be seen that single reference channel of pulse is used as by than reference channel one by one, by by than reference channel in addition to invalid data area Data area in each pulse window as one than time zone, obtained other each reference channels by than in time zone Threshold point；Judge whether the single of other reference channels is equal to 0 by the quantity than the threshold point in time zone, if it is, thinking this By than the pulse combined success in time zone, following steps are otherwise executed；Judge whether list is equal to 2 by the quantity than the threshold point in time zone, if being not equal to 2, then it is assumed that this is by than the time Pulse combined failure in region executes following steps if being equal to 2；Judge single time for whether being later than rear threshold point by the time than the preceding threshold point in two threshold points in time zone, If it is, thinking that this is failed than the pulse combined in time zone, following steps are otherwise executed；Judge whether the same of all reference channels is greater than interval than the difference between the peak value of pulse moment in time zone Threshold value, if it is, thinking that this is failed than the pulse combined in time zone, otherwise it is assumed that this is by than the arteries and veins in time zone Punching is combined successfully.
- 8. method as claimed in claim 5, which is characterized in that the valid data area is pulse combined successfully all correspondences The superposition of the time zone of pulse window.
- 9. method according to any one of claims 1 to 4, which is characterized in that in the significant figure for determining multiple reference channels Behind area further include:Whether find that pulse determines the logical value of each reference channel according to each reference channel；Logical value and logical algorithm based on each reference channel carry out logical operation；Determined whether to carry out pulse recognition to the pending data in all channels according to logic operation result.
- 10. method as claimed in claim 5, which is characterized in that also wrapped behind the valid data area for determining multiple reference channels It includes:Whether find that pulse determines the logical value of each reference channel according to each reference channel；Logical value and logical algorithm based on each reference channel carry out logical operation；Determined whether to carry out pulse recognition to the pending data in all channels according to logic operation result.
- 11. method as claimed in claim 6, which is characterized in that also wrapped behind the valid data area for determining multiple reference channels It includes:Whether find that pulse determines the logical value of each reference channel according to each reference channel；Logical value and logical algorithm based on each reference channel carry out logical operation；Determined whether to carry out pulse recognition to the pending data in all channels according to logic operation result.
- 12. the method for claim 7, which is characterized in that also wrapped behind the valid data area for determining multiple reference channels It includes:Whether find that pulse determines the logical value of each reference channel according to each reference channel；Logical value and logical algorithm based on each reference channel carry out logical operation；Determined whether to carry out pulse recognition to the pending data in all channels according to logic operation result.
- 13. method according to claim 8, which is characterized in that also wrapped behind the valid data area for determining multiple reference channels It includes:Whether find that pulse determines the logical value of each reference channel according to each reference channel；Logical value and logical algorithm based on each reference channel carry out logical operation；Determined whether to carry out pulse recognition to the pending data in all channels according to logic operation result.
- The pulse recognition device of reference channel more than 14., it is characterised in that include:Data acquisition unit, the signal for acquiring multiple reference channel outputs obtain the pending data of each reference channel, institute The signal for stating reference channel output is that the optical information issued after being optically excited by the tested particle that reference channel is collected is converted into Electric signal；Pulse finds unit, for pending data and characteristic threshold value corresponding with the reference channel based on each single reference channel Judge whether to find pulse, the characteristic threshold value is the threshold value of the feature of interest of particle of interest, and the discovery pulse refers to Detect that peak value of pulse is greater than the pulse of characteristic threshold value；Single channel dead space determination unit, for single reference channel for finding pulse, the pulse to be identified based on discovery is true Invalid data area in the pending data of the fixed list reference channel；Dead space Unified Element, for unifying the invalid data of multiple reference channels according to the invalid data area of each single reference channel The beginning and ending time in area；Effective district determination unit determines the valid data of multiple reference channels based on the invalid data area after the unified beginning and ending time Area；Pulse recognition unit, for carrying out pulse recognition to the pulse in valid data area when carrying out pulse recognition, to invalid number Pulse recognition is no longer carried out according to the pulse in area.
- 15. device as claimed in claim 14, which is characterized in that single channel dead space determination unit includes:Pulse window determines subelement, for determining that the pulse window of pulse to be identified, the pulse window are the region that pulse continues；First judgment sub-unit, for judging the pulse window of current pulse to be identified and the arteries and veins of pulse to be identified adjacent before and after it Rush whether window is overlapped, if it is, the pulse window region of overlapping will be related to as invalid data area；Second judgment sub-unit, whether the pulse width for judging pulse to be identified abnormal, if it is, by the exception to Identify the pulse window region of pulse as invalid data area.
- 16. device as claimed in claim 15, which is characterized in that dead space Unified Element includes:Longitudinal pollution subelement, for one by one using single reference channel with invalid data area as by than reference channel with it is other Reference channel compares, and the pending data region of other reference channels is neutralized by the start-stop in the invalid data area than reference channel The time identical period is as invalid data area；Laterally pollution subelement, for judging whether the invalid data area of each single reference channel pulse window adjacent with front and back has weight It is folded, if so, the pulse window region for being then related to overlapping is also used as invalid data area；Third judgment sub-unit, for judging whether the invalid data area of each single reference channel has unified beginning and ending time, root It is judged that result is determined by longitudinally polluting subelement and laterally pollution subelement works on or end loop.
- 17. the device as described in any one of claim 14 to 16, which is characterized in that effective district determination unit is used for according to same Similitude rule of one particle between the pulse that multiple reference channels are formed, by removing invalid data to multiple reference channels Data area outside area carries out pulse combined, and the valid data area of multiple reference channels, institute are determined according to pulse combined result Valid data area is stated including at least the successful pulse window region of pulse combined.
- 18. device as claimed in claim 17, which is characterized in that the similitude rule includes: pair of multiple reference channels It answers the pulse in pulse window to be no more than 1, will be seen that single reference channel of pulse is used as by than reference one by one in pulse combined Channel, using by the pulse window in the data area in addition to invalid data area than reference channel as by than time zone, it is described Effective district determination unit includes:Threshold point obtain subelement, for obtain other each reference channels by than the threshold point in time zone；4th judgment sub-unit, for judge other reference channels it is single by the quantity than the threshold point in time zone whether etc. In 0, if it is, thinking this by than the pulse combined success in time zone；5th judgment sub-unit, in the in varying numbers in 0 when of the 4th judgment sub-unit judgment threshold point, judge it is single by than when Between the quantity of threshold point in region whether be equal to 2, if being not equal to 2, then it is assumed that this is by than the pulse combined in time zone Failure；6th judgment sub-unit, for judging two threshold values when list is equal to 2 by the quantity than the threshold point in time zone The time of preceding threshold point in point whether prior to rear threshold point time, if it is, thinking this by than the arteries and veins in time zone Punching is combined successfully, otherwise it is assumed that this is failed than the pulse combined in time zone.
- 19. device as claimed in claim 17, which is characterized in that the similitude rule includes: pair of multiple reference channels The pulse in pulse window is answered no more than 1 and peak value moment is close, will be seen that the single with reference to logical of pulse one by one in pulse combined Road is used as by than reference channel, using by the pulse window in the data area in addition to invalid data area than reference channel as by than Time zone, the effective district determination unit include:Threshold point obtain subelement, for obtain other each reference channels by than the threshold point in time zone；4th judgment sub-unit, for judge other reference channels it is single by the quantity than the threshold point in time zone whether etc. In 0, if it is, thinking this by than the pulse combined success in time zone；5th judgment sub-unit, in the in varying numbers in 0 when of the 4th judgment sub-unit judgment threshold point, judge it is single by than when Between the quantity of threshold point in region whether be equal to 2, if being not equal to 2, then it is assumed that this is by than the pulse combined in time zone Failure；6th judgment sub-unit, for being equal in the 5th judgment sub-unit judgement list by the quantity than the threshold point in time zone Judge when 2 the preceding threshold point in two threshold points time whether prior to rear threshold point time, if preceding threshold point when Between be later than time of rear threshold point, then it is assumed that this is failed than the pulse combined in time zone；7th judgment sub-unit, for judging time of the time prior to rear threshold point of preceding threshold point in the 6th judgment sub-unit When, judge whether the same of all reference channels is greater than interval threshold than the difference between the peak value of pulse moment in time zone Value, if it is, thinking that this is failed than the pulse combined in time zone, otherwise it is assumed that this is by than the pulse in time zone It combines successfully.
- 20. device as claimed in claim 17, which is characterized in that the valid data area is that pulse combined is successfully all right Answer the superposition of the time zone of pulse window.
- 21. a kind of particle analyzer, it is characterised in that include:Excitation light source, for providing the exciting light for irradiating tested particle；Flow chamber, for providing tested particle illuminated place；Light collecting device, for collecting the optical information issued after tested particle is optically excited, the light collecting device includes multiple Reference channel；WithDevice as described in any one of claim 14-20.
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| ES2924076T3 (en) * | 2015-12-18 | 2022-10-04 | Abbott Lab | Particle detection methods and systems for your practice |
| CN107101983B (en) * | 2017-04-25 | 2019-11-08 | 广东永诺医疗科技有限公司 | Droplet multichannel fluorescence synchronous waveform method and device |
| CN107290253B (en) * | 2017-06-27 | 2019-06-04 | 迈克医疗电子有限公司 | The processing method and processing device of pattern detection data |
| CN111122420B (en) * | 2018-10-31 | 2025-05-27 | 深圳市帝迈生物技术有限公司 | Synchronous identification method and device for multi-channel pulse signals, and particle detection system |
| CN112881351A (en) * | 2019-11-30 | 2021-06-01 | 深圳市帝迈生物技术有限公司 | Particle detection method and device based on pulse recognition and storage medium |
| CN111235023A (en) * | 2020-03-25 | 2020-06-05 | 梨薯(厦门)科技有限公司 | Single particle detection method based on multi-channel triggering |
| CN115398209B (en) * | 2020-04-13 | 2025-08-26 | 深圳迈瑞生物医疗电子股份有限公司 | Cell analysis method, cell analyzer, and computer-readable storage medium |
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