CN109613106A - Multifunctional modular sample pre-treatments device and its application method for high-throughput Mass Spectrometer Method - Google Patents
Multifunctional modular sample pre-treatments device and its application method for high-throughput Mass Spectrometer Method Download PDFInfo
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/62—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating the ionisation of gases, e.g. aerosols; by investigating electric discharges, e.g. emission of cathode
- G01N27/64—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating the ionisation of gases, e.g. aerosols; by investigating electric discharges, e.g. emission of cathode using wave or particle radiation to ionise a gas, e.g. in an ionisation chamber
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
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Abstract
A kind of multifunctional modular sample pre-treatments device and its application method for high-throughput Mass Spectrometer Method, device of the present invention includes appliance stand, extract module, filtering module, four parts of sample collection module, wherein: being connected between device modules of the present invention by interface channel, and the circulation of sample is controlled by plug, appliance stand is used to support and fixes modules, device of the present invention the multiple modules of permutation and combination can be realized simultaneously to multiple complex environments and biological sample progress pre-treatment simultaneously, and required sample size is minimum, the quick of small molecule compound may be implemented, high-throughput and highly sensitive detection, device of the present invention is by sample pre-treatments and Mass Spectrometer Method modularization, sample can be directly added drop-wise on commercialization MALDI target plate after pre-treatment, save sample preparation time, simplify operating procedure, it improves Detection efficiency.
Description
Technical field
The invention belongs to pre-treatment fields, relate more specifically to a kind of multifunctional modular for high-throughput Mass Spectrometer Method
Sample pre-treatments device and its application method.
Background technique
Substance assistant laser desorpted time-of-flight mass spectrometry (MALDI-TOF MS) technology is a kind of from 80 years 20th century
Quick, simple, the high-throughput analytical technique of mass spectrum that generation grows up.Its principle is mainly by by determinand and selected base
The solution of matter compound mixes, and forms cocrystallization with matrix after the solvent is volatilized, at this time with the laser irradiation of certain pulse, easily inhales
The matrix for receiving laser energy absorbs laser energy first and it is passed to determinand by cocrystallization again, excites determinand molecule
Ionization detects it by mass spectrograph after accelerating in tof tube.Flight time and mass-to-charge ratio, which exist, to be positively correlated, and matter is passed through
The molecular weight of determinand just can be detected in spectrogram.Since its Mass Spectrometer Method range is wide, does not need chromatography and separated, it can be to pole
Its complicated sample is analyzed.
And in the analysis and detection of complex sample, Sample Pretreatment Technique is most important.In recent years, before various samples
Reason technology flourishes, the pre-treatment applied to various types sample.Such as Solid Phase Extraction, solid phase microextraction, micro- Solid Phase Extraction, magnetic
The technologies such as property extraction, ultrasound on extracting, ultrafiltration and dialysis are widely used in complex environment sample and biological sample.
But due to time for sample pretreatment it is long, it is complicated for operation, be difficult to realize the disadvantages of high-throughput, automation, researcher is also always
Think a variety of different methods, finds new technology to reduce the time of pre-treatment or even avoid sample pre-treatments.
Summary of the invention
Based on problem above, the main purpose of the present invention is to provide a kind of multi-functional moulds for high-throughput Mass Spectrometer Method
Block sample pre-treatments device and its application method, for solving at least one of above technical problem.
To achieve the goals above, the invention proposes a kind of multifunctional modular samples that will be used for high-throughput Mass Spectrometer Method
Product pre-treatment device and its application method, comprising: extraction module, filtering module, sample collection module and appliance stand；
The hollow column tube structure that the extraction module is vertically arranged, the extraction module top are equipped with the first opening, institute
The first opening is stated equipped with the first sealing cover, the opening downside is nearby equipped with acclivitous injection port；
The filtering module includes upper filtering module and lower filtering module, and upper filtering module and lower filtering module are vertical
The hollow column tube structure being arranged, the upper filtering module top are equipped with the second opening, and second opening is equipped with sealing cover, institute
Filtering module bottom end is stated equipped with annular protrusion, it is recessed that the lower filtering module top is equipped with annular compatible with the protrusion
Slot is placed with filter membrane and fixed with the protrusion on the groove；
The bottom of the extraction module is connected to by the hollow column tube of first level with the top of the upper filtering module, described
The hollow column tube of first level is equipped with the first plug；
The hollow column tube structure that the sample collection module is vertically arranged, sample collection module top are equipped with third
Opening, the third opening are equipped with third sealing cover, and third sealing cover one end is equipped with nozzle and is used to connect vacuum pump, institute
There is vertical conical pipeline in the bottom end for stating sample collection module；
The bottom of the lower filtering module is connected to by the second flat hollow column tube with the top of the sample collection module,
The second flat hollow column tube is equipped with the second plug；
Described device bracket is used to support the extraction module, the filtering module and the sample collection module, described
There is the card slot for placing and fixing MALDI target plate among appliance stand, the sample collection module is consolidated by described device bracket
Above the card slot, so that treated, sample is added drop-wise on MALDI target plate by the conical pipeline.
Further, the length of the hollow column tube of the extraction module, the filtering module and the sample collection module
It is 1.5-5cm, internal diameter is 0.5-3cm, and outer diameter is 0.8-5cm.
Further, compatible with MALDI target plate for placing the card slot of MALDI target plate among described device bracket, and lead to
Jackscrew is crossed to fix.
Further, in use, the third sealing cover is controlled to a vacuum pump, auxiliary power is provided for the transfer of sample.
Further, in order to guarantee that sample is accurately added drop-wise on the corresponding target spot of MALDI target plate, the sample collection mould
The diameter in the conical pipeline exit of block is 0.5-1mm.
Further, the third of the folding between control module is provided on the conical pipeline of the sample collection module bottom
Plug.
Further, the extraction module, the filtering module and the sample collection module are arranged side by side more
Quantity that is a, can adjusting while use according to the needs of sample pre-treatments, to realize high-throughput pre-treatment and detection.
Further, described device bracket can be according to the extraction module, the filtering module and the sample collection mould
The quantity that block uses simultaneously is sized.
Further, first plug and second plug are according to the extraction module, the filtering module and institute
It states sample collection module while the quantity used is single-rotatable plug or row's plug.
Further, the extraction module, the filtering module and the sample collection module be arranged side by side multiple
When, the plug of the folding between control module is row's plug, controls the circulation of sample by the row's of promotion plug at this time.
Further, the Module part by 3D printing rapid shaping, precise forming, machining, cold and hot working or
Manual shaping technology is formed.
Further, the Module part includes constant and micro environmental sample and biological sample for the sample of processing
Product, preferably micro biological sample.
On the other hand, the application provide it is a kind of according to Module part above-mentioned to sample to be tested carry out ground substance assistant laser
The method of desorption ionization time-of-flight mass spectrometry detection, comprising the following steps:
Sample to be tested and fiber material addition are used for high pass as described in any one of claims 1 to 12 by step 1
The multifunctional modular sample pre-treatments device and its application method for measuring Mass Spectrometer Method are passing through the extraction module, the mistake
After the completion of filtering module and the sample collection resume module, will finally it be received by controlling first plug and second plug
The sample drop of collection is on the corresponding target spot of commercialization MALDI target plate；
Step 2 carries out mass spectrum to the sample to be tested using substance assistant laser desorpted-time-of-flight mass spectrometry instrument
Detection.
Further, in step 1, extraction module is added in sample to be tested and fiber material, is controlled after extracting 30min
Mixed liquor is introduced filtering module by the first plug, keeps all plugs in the open state, by the third sealing cover
After nozzle is controlled to a vacuum pump and filters 30s, the filtrate filtered out is discarded；
If the fiber material can be used as the substance assistant laser desorpted ionization analyte of MALDI, filter residue can be taken off putting
Enter sample collection device, and the ultrapure water that 10-200 μ L is added is dispersed into suspension under ultrasonic wave added；If the extraction material
Material not can be used as the substance assistant laser desorpted ionization analyte of MALDI, then first places filter membrane in filtering module groove,
And upper filtering module and lower filtering module are snapped together；
Then the eluent of 0.5-3mL is added in filtering module, ultrasonic wave added 10min passes through the third sealing cover
After the vacuum pump of upper connection filters 30s, filter membrane is discarded；The second plug is finally controlled by Sample introduction sample collection module, and will
It is added drop-wise on the commercialization MALDI target plate being fixed on appliance stand.
A kind of multifunctional modular sample pre-treatments device for high-throughput Mass Spectrometer Method proposed by the present invention and its make
It is had the advantages that with method
1, the multifunctional modular sample pre-treatments device and its application method for high-throughput Mass Spectrometer Method of the invention
Modules shape, structure it is flexibly controllable, can be assembled according to the pre-treatment demand of different samples, to realize different
Pre-treatment operation, it is easy to operate, it is convenient and efficient.
2, the multifunctional modular sample pre-treatments device and its application method for high-throughput Mass Spectrometer Method of the invention
The multiple modules of permutation and combination it can realize simultaneously while pre-treatment is carried out to multiple complex environments and biological sample, realize quickly high
The Mass Spectrometer Method of flux.
3, the multifunctional modular sample pre-treatments device and its application method for high-throughput Mass Spectrometer Method of the invention
Volume is minimum, and required sample size is few, passes through the dense of the enrichment of extraction module, the separation of filtering module and sample collection module
Contracting, may be implemented the highly sensitive Mass Spectrometer Method of small molecule compound, and detection limit can reach ppt and be even lower than ppt rank.
4, the multifunctional modular sample pre-treatments device and its application method for high-throughput Mass Spectrometer Method of the invention
By sample pre-treatments and Mass Spectrometer Method modularization, device is compatible with commercialization MALDI target plate, can simplify operating procedure, saves
Sample preparation time improves detection efficiency；
5, sample pre-treatments of the invention and high-throughput Mass Spectrometer Method Module part are modularized design, it is easy to disassemble and
Assembling, can also further increase other function module, have good scalability and compatibility.
6, the multifunctional modular sample pre-treatments device and its application method for high-throughput Mass Spectrometer Method of the invention
With at low cost, manufacturing process is simple, signal stabilization, high-throughput, easy to use feature, and have continue to optimize can
Energy；
Detailed description of the invention
Before Fig. 1 and Fig. 2 is the multifunctional modular sample for high-throughput Mass Spectrometer Method that one embodiment of the invention proposes
The print example of processing apparatus and its application method, wherein Fig. 1 is the front view that ten modules use simultaneously, Fig. 2 (a) and 2
(b) be respectively the device main view and top view, Fig. 2 (c) and 2 (d) be appliance stand structure, Fig. 2 (e) be ten modules
Five platoon plugs when using simultaneously for control, Fig. 2 (f) are commercialization MALDI target plate；
Before Fig. 3 is the multifunctional modular sample for high-throughput Mass Spectrometer Method proposed using one embodiment of the invention
Device and its application method are managed to the Mass Spectrometer Method result of 1 μ L hybrid standard sample, Fig. 3 (a) and 3 (b) is in anion respectively
It is detected under mode and positive ion mode；
Before the multifunctional modular sample for high-throughput Mass Spectrometer Method for using one embodiment of the invention to propose in Fig. 4
Device and its application method are managed to actual lung perfusion liquid Mass Spectrometer Method result, wherein Fig. 4 (a) and 4 (b) be respectively bear from
It is detected under subpattern and positive ion mode；
Before the multifunctional modular sample for high-throughput Mass Spectrometer Method for using one embodiment of the invention to propose in Fig. 5
Device and its application method are managed to actual serum mark-on sample Mass Spectrometer Method result, wherein Fig. 5 (a) and 5 (b) be respectively
It is detected under negative ion mode and positive ion mode；
Before the multifunctional modular sample for high-throughput Mass Spectrometer Method for using one embodiment of the invention to propose in Fig. 6
Device and its application method are managed to actual single drop whole blood mark-on sample Mass Spectrometer Method result, wherein Fig. 6 (a) and 6 (b) is respectively
It is to be detected under negative ion mode and positive ion mode；
Before the multifunctional modular sample for high-throughput Mass Spectrometer Method for using one embodiment of the invention to propose in Fig. 7
Device and its application method are managed to actual single drop whole blood sample perfluorochemical mass spectrum screening results.
Specific embodiment
To make the objectives, technical solutions, and advantages of the present invention clearer, below in conjunction with specific embodiment, and reference
Attached drawing, the present invention is described in further detail.
High-throughput mass-spectrometric technique applied to complex sample analysis learns research, environment and health etc. for food safety, group
Many fields all have extremely important effect.And pretreatment technology is most important one component part, wherein place before simplifying
The step of reason, realizes high-throughput, modularization, is that barrier in the pretreatment technology of complex sample and people are urgently to be solved
Problem.Therefore, the invention proposes a kind of multifunctional modular sample pre-treatments device for high-throughput Mass Spectrometer Method and its
Application method, including extraction module 2, filtering module 3,4, sample collection module 5 and appliance stand 8；
The hollow column tube structure that the extraction module 2 is vertically arranged, 2 top of extraction module are equipped with the first opening,
First opening is equipped with the first sealing cover, is nearby equipped with acclivitous injection port 1 on the downside of the opening；
The filtering module 3,4 includes upper filtering module 3 and lower filtering module 4, upper filtering module 3 and lower filtering module 4
The hollow column tube structure being vertically arranged, upper 3 top of filtering module are equipped with the second opening, and second opening is equipped with
Sealing cover, upper 3 bottom end of filtering module are equipped with annular protrusion, and lower 4 top of filtering module is equipped with mutually suitable with the protrusion
The annular groove matched is placed with filter membrane 6 and fixed with the protrusion on the groove；
The bottom of the extraction module 2 is connected to by the hollow column tube of first level with the top of the upper filtering module 3, institute
The hollow column tube of first level is stated equipped with the first plug 7；
The hollow column tube structure that the sample collection module 5 is vertically arranged, 5 top of sample collection module are equipped with the
Three openings, the third opening are equipped with third sealing cover, and third sealing cover one end is equipped with nozzle and is used to connect vacuum pump,
There is vertical conical pipeline in the bottom end of the sample collection module 5；
The bottom of the lower filtering module 4 is connected by the top of the second flat hollow column tube and the sample collection module 5
Logical, the second flat hollow column tube is equipped with the second plug 9；
Described device bracket 8 is used to support the extraction module 2, the filtering module 3,4 and the sample collection module
5, there is the card slot for placing and fixing MALDI target plate among described device bracket 8, the sample collection module 5 is by the dress
It sets bracket 8 to be fixed on above the card slot, so that treated, sample is added drop-wise on MALDI target plate by the conical pipeline.
Further, the hollow column tube of the extraction module 2, the filtering module 3,4 and the sample collection module 5
Length is 1.5-5cm, and internal diameter is 0.5-3cm, and outer diameter is 0.8-5cm；In some embodiments of the invention, the extraction
The length of the hollow column tube of modulus block 2, the filtering module 3,4 and the sample collection module 5 is 4cm, and pipe inside radius is
0.74cm, pipe outside diameter 1cm.
It is compatible with MALDI target plate for placing the card slot of MALDI target plate among described device bracket 8 and solid by jackscrew
It is fixed.
In use, the third sealing cover is controlled to a vacuum pump, auxiliary power is provided for the transfer of sample.
In order to guarantee that sample is accurately added drop-wise on the corresponding target spot of MALDI target plate, the taper of the sample collection module 5
The diameter of pipeline exit is 0.5-1mm.Preferably, the vertical conical pipeline exit diameter of 5 bottom end of sample collection module is
0.8mm。
The third plug of the folding between control module is provided on the conical pipeline of 5 bottom of sample collection module.
The extraction module 2, the filtering module 3,4 and the sample collection module 5 be it is arranged side by side multiple, can
According to the quantity that the needs of sample pre-treatments are adjusted while being used, to realize high-throughput pre-treatment and detection.Of the invention one
In a little embodiments, while 10 modules are used, it may be assumed that the extraction module 2, the filtering module 3,4 and the sample collection
Module 5 is 10 arranged side by side, and appliance stand is also adjusted to 10 modules that are sustainable while using.
Described device bracket 8 can be same according to the extraction module 2, the filtering module 3,4 and the sample collection module 5
When the quantity that uses be sized.
First plug and second plug are according to the extraction module 2, the filtering module 3,4 and the sample
The quantity that collection module 5 uses simultaneously is single-rotatable plug or row's plug.In some embodiments of the invention, opening between control module
The plug of conjunction is 5 platoon plugs, and the circulation of sample is controlled by the row's of promotion plug.
The extraction module 2, the filtering module 3,4 and the sample collection module 5 be arranged side by side it is multiple when, control
The plug of the folding of intermodule processed is row's plug, controls the circulation of sample by the row's of promotion plug at this time.
The Module part passes through machining, cold and hot working, precise forming, 3D printing rapid shaping or offhand skill
Art is formed.Preferably, above-mentioned device is fabricated by 3D printing.
Sample of the Module part for processing includes constant and micro environmental sample and biological sample, preferably
Micro biological sample.
In another embodiment of the application, the application provide it is a kind of according to Module part above-mentioned to sample to be tested
The method for carrying out substance assistant laser desorpted ionization tandem flight time mass spectrum detection, comprising the following steps:
Sample to be tested and fiber material addition are used for high pass as described in any one of claims 1 to 12 by step 1
The multifunctional modular sample pre-treatments device and its application method for measuring Mass Spectrometer Method are passing through the extraction module 2, the mistake
After the completion of filtering module 3,4 and the sample collection module 5 processing, sample drop that will finally be collected by controlling the third plug
On the corresponding target spot of commercialization MALDI target plate；
Step 2 carries out mass spectrum to the sample to be tested using substance assistant laser desorpted-time-of-flight mass spectrometry instrument
Detection.
Further, in step 1, extraction module 2 is added in sample to be tested and fiber material, is controlled after extracting 30min
It makes the first plug 7 and mixed liquor is introduced into filtering module 3,4, keep all plugs in the open state, sealed by the third
After the nozzle covered is controlled to a vacuum pump and filters 30s, the filtrate filtered out is discarded；
If the fiber material can be used as the substance assistant laser desorpted ionization analyte of MALDI, filter residue can be taken off putting
Enter sample collection device, and the ultrapure water that 10-200 μ L is added is dispersed into suspension under ultrasonic wave added；If the extraction material
Material not can be used as the substance assistant laser desorpted ionization analyte of MALDI, then first places filter in 3,4 groove of filtering module
Film, and upper filtering module 3 and lower filtering module 4 are snapped together；
Then the eluent of 0.5-3mL is added in filtering module 3,4, ultrasonic wave added 10min is sealed by the third
After the vacuum pump suction filtration 30s for covering connection, filter membrane is discarded；The second plug 9 is finally controlled by Sample introduction sample collection module 5,
And it is added dropwise on the commercialization MALDI target plate being fixed on appliance stand.
The Module part of the application, accessible sample include the whole blood sample singly dripped, and the small molecule of detection can reach
The detection limit of ppt rank is even lower than to ppt rank.
Below by way of specific embodiment, to the multifunctional modular sample proposed by the present invention for high-throughput Mass Spectrometer Method
Pre-treatment device and its application method are described in detail.
Embodiment
As shown in Figure 1, the present embodiment proposes a kind of multifunctional modular sample pre-treatments for high-throughput Mass Spectrometer Method
Device and its application method, in the present embodiment, the device are fabricated by 3D printing, and main material is photosensitive resin
And rubber；The entirety of the device is assembled by nine parts, as shown in Figure of abstract, wherein 1 is injection port, and 2 be extraction mould
Block, 3,4 top half and lower half portion for filtering module, 5 be sample collection module, and 6 be filter membrane, and 7 be row's plug, and 8 be device
Bracket.Target plate is for holding the sample to be tested for needing to be detected by MALDI-TOF mass spectrograph.Wherein, such as Fig. 1 and Fig. 2 institute
Show, Fig. 1 is the front view that ten modules use simultaneously, and Fig. 2 (a) and 2 (b) is respectively the main view and top view of the device, Fig. 2
(c) and 2 (d) be appliance stand structure, Fig. 2 (e) is five platoon plugs when ten modules use simultaneously for control, Fig. 2 (f)
To be commercialized MALDI target plate.
Using the present embodiment propose for high-throughput Mass Spectrometer Method multifunctional modular sample pre-treatments device and its
Application method and MALDI-TOF mass spectrograph are 0.9 μ g/mL bisphenol S to concentration；Concentration is 4.5 μ g/mL 2,2', 4,4'- tetrabromos
Biphenyl Ether；Concentration is the pentachlorophenol of 0.9 μ g/mL；Concentration is 4.5 μ g/mL estradiol；Concentration is that the perfluor of 0.09 μ g/mL is pungent
Base sulfonic acid；Concentration is the tetrabromobisphenol A of 0.9 μ g/mL；Concentration is the trivalent arsenic of 1.4 μ g/mL；Concentration is the N- ten of 0.4 μ g/mL
Six alkyl-N, N- dimethyl benzyl ammonium chlorides；Concentration is the dodecyldimethylamine ammonium chloride of 0.4 μ g/mL；Concentration is 0.4 μ g/
The dodecyl benzyl dimethyl ammonium chloride of mL；Concentration is the cetyl trimethylammonium bromide of 0.09 μ g/mL；Concentration is 0.09
The N of μ g/mL, N, N- trimethyl -1- Tetra-n-decylammonium bromide are tested and analyzed.The sample for drawing 20 μ L with liquid-transfering gun first is dilute
In the device for releasing the present embodiment equipped with 980 μ L water, the fiber material of 100 μ L 10mg/mL is added；Treated sample drop
Onto the target plate of connection, target plate is put into MALDI-TOF mass spectrograph to the instrument type for detecting, using after sample exsiccation
It number is Bruker DaltonicsAutoflex III Smartbean MALDI-TOF mass spectrograph, frequency of use is 100Hz
355nm Nd:YAG, laser power are set as 40%, and anion is respectively adopted and positive ion mode is detected.Measurement result is such as
Shown in Fig. 3, Fig. 4, Fig. 5, Fig. 6 and Fig. 7, wherein Fig. 3 is the Mass Spectrometer Method of 1 μ L hybrid standard sample as a result, Fig. 4 is actual
Lung perfusion liquid Mass Spectrometer Method is as a result, Fig. 5 is actual serum mark-on sample Mass Spectrometer Method as a result, Fig. 6 is actual single drop whole blood
Mark-on sample Mass Spectrometer Method result, Fig. 7 are actual single drop whole blood sample Mass Spectrometer Method result.From Fig. 3~6 as can be seen that
The 12 kinds of organic matters surveyed have stronger detection signal, it was demonstrated that the device of the present embodiment can be by sample pre-treatments and high-throughput mould
Block.From figure 7 it can be seen that screening 3 kinds of perfluorochemicals can be gone out from single drop whole blood sample, it was demonstrated that the device of the present embodiment
Not only can be by sample pre-treatments and high-throughput detection module, and have the function of the non-target compound of mass spectrum screening, it can be with
Further extend its application.
As can be seen from the above embodiments, using the multifunctional modular proposed by the present invention for high-throughput Mass Spectrometer Method
Sample pre-treatments device and its application method the multiple modules of permutation and combination can be realized simultaneously to multiple complex environments and life simultaneously
Object sample carries out pre-treatment, realizes the Mass Spectrometer Method of fast high-flux, and required sample size is minimum, and small molecule may be implemented
Close the highly sensitive detection of object, detection limit can reach ppt and be even lower than ppt rank, and device of the present invention is by sample pre-treatments and matter
Detection module is composed, device is compatible with commercialization MALDI target plate, can simplify operating procedure, saves sample preparation time, improves
Detection efficiency.Device of the present invention is easy to disassemble and assembles, easy to use, and has the possibility continued to optimize, therefore has wide
Wealthy application prospect.
Particular embodiments described above has carried out further in detail the purpose of the present invention, technical scheme and beneficial effects
Describe in detail bright, it should be understood that the above is only a specific embodiment of the present invention, is not intended to restrict the invention, it is all
Within the spirit and principles in the present invention, any modification, equivalent substitution, improvement and etc. done should be included in protection of the invention
Within the scope of.
Claims (14)
1. a kind of multifunctional modular sample pre-treatments device and its application method that will be used for high-throughput Mass Spectrometer Method, feature
It is, comprising: extraction module (2), filtering module (3,4), sample collection module (5) and appliance stand (8)；
The hollow column tube structure that extraction module (2) is vertically arranged, the extraction module (2) top are equipped with the first opening,
First opening is equipped with the first sealing cover, is nearby equipped with acclivitous injection port (1) on the downside of the opening；
The filtering module (3,4) includes upper filtering module (3) and lower filtering module (4), upper filtering module (3) and lower filter module
The hollow column tube structure that block (4) is vertically arranged, upper filtering module (3) top are equipped with the second opening, and described second opens
Mouth be equipped with sealing cover, upper filtering module (3) bottom end be equipped with annular protrusion, lower filtering module (4) top be equipped with
The protrusion compatible annular groove is placed with filter membrane (6) and fixed with the protrusion on the groove；
The bottom of extraction module (2) is connected to by the hollow column tube of first level with the top of the upper filtering module (3), institute
The hollow column tube of first level is stated equipped with the first plug (7)；
The hollow column tube structure that the sample collection module (5) is vertically arranged, sample collection module (5) top are equipped with the
Three openings, the third opening are equipped with third sealing cover, and third sealing cover one end is equipped with nozzle and is used to connect vacuum pump,
There is vertical conical pipeline in the bottom end of the sample collection module (5)；
The bottom of the lower filtering module (4) is connected by the top of the second flat hollow column tube and the sample collection module (5)
Logical, the second flat hollow column tube is equipped with the second plug (9)；
Described device bracket (8) is used to support the extraction module (2), the filtering module (3,4) and the sample collection mould
Block (5), the intermediate card slot having for placing and fixing MALDI target plate of described device bracket (8), the sample collection module (5)
It is fixed on above the card slot by described device bracket (8), so that treated, sample is added drop-wise to by the conical pipeline
On MALDI target plate.
2. multifunctional modular sample pre-treatments device according to claim 1 for high-throughput Mass Spectrometer Method and its making
With method, which is characterized in that the extraction module (2), the filtering module (3,4) and the sample collection module (5) sky
The length of stem pipe is 1.5-5cm, and internal diameter is 0.5-3cm, and outer diameter is 0.8-5cm.
3. multifunctional modular sample pre-treatments device according to claim 1 or 2 for high-throughput Mass Spectrometer Method and
Its application method, which is characterized in that the card slot and MALDI target plate among described device bracket (8) for placing MALDI target plate are simultaneous
Hold, and is fixed by jackscrew.
4. multifunctional modular sample pre-treatments device according to claim 1 for high-throughput Mass Spectrometer Method and its making
With method, which is characterized in that in use, the third sealing cover is controlled to a vacuum pump, provide auxiliary power for the transfer of sample.
5. multifunctional modular sample pre-treatments device according to claim 1 or 2 for high-throughput Mass Spectrometer Method and
Its application method, which is characterized in that in order to guarantee that sample is accurately added drop-wise on the corresponding target spot of MALDI target plate, the sample
The diameter in the conical pipeline exit of collection module (5) is 0.5-1mm.
6. the multifunctional modular sample pre-treatments device described in one of -5 for high-throughput Mass Spectrometer Method according to claim 1
And its application method, which is characterized in that be provided between control module on the conical pipeline of sample collection module (5) bottom
The third plug of folding.
7. the multifunctional modular sample pre-treatments device described in one of -6 for high-throughput Mass Spectrometer Method according to claim 1
And its application method, which is characterized in that the extraction module (2), the filtering module (3,4) and the sample collection module
It (5) is multiple, the quantity that can be adjusted while use according to the needs of sample pre-treatments, before realizing high throughput arranged side by side
Processing and detection.
8. the multifunctional modular sample pre-treatments device described in one of -7 for high-throughput Mass Spectrometer Method according to claim 1
And its application method, which is characterized in that described device bracket (8) can according to the extraction module (2), the filtering module (3,
4) quantity used simultaneously with the sample collection module (5) is sized.
9. the multifunctional modular sample pre-treatments device described in one of -8 for high-throughput Mass Spectrometer Method according to claim 1
And its application method, which is characterized in that first plug and second plug are according to the extraction module (2), the mistake
The quantity that filter module (3,4) and the sample collection module (5) use simultaneously is single-rotatable plug or row's plug.
10. multifunctional modular sample pre-treatments device according to claim 9 for high-throughput Mass Spectrometer Method and its
Application method, which is characterized in that the extraction module (2), the filtering module (3,4) and the sample collection module (5) are
When arranged side by side multiple, the plug of the folding between control module is row's plug, controls the stream of sample by the row's of promotion plug at this time
It is logical.
11. the multifunctional modular sample pre-treatments device described in one of -10 for high-throughput Mass Spectrometer Method according to claim 1
Part and its application method, which is characterized in that the Module part passes through 3D printing rapid shaping, precise forming, machining, cold
Hot-working or manual shaping technology are formed.
12. the multifunctional modular sample pre-treatments device described in one of -11 for high-throughput Mass Spectrometer Method according to claim 1
Part and its application method, which is characterized in that sample of the Module part for processing includes constant and micro environment sample
Product and biological sample, preferably micro biological sample.
13. a kind of Module part according to one of preceding claims 1-12 carries out ground substance assistant laser to sample to be tested
The method of desorption ionization time-of-flight mass spectrometry detection, which comprises the following steps:
Sample to be tested and fiber material addition are used for high-throughput matter as described in any one of claims 1 to 12 by step 1
The multifunctional modular sample pre-treatments device and its application method for composing detection are passing through the extraction module (2), the filtering
After the completion of module (3,4) and the sample collection module (5) processing, sample that will finally be collected by controlling the third plug
Drop is on the corresponding target spot of commercialization MALDI target plate；
Step 2 carries out mass spectrum inspection to the sample to be tested using substance assistant laser desorpted-time-of-flight mass spectrometry instrument
It surveys.
14. according to the method for claim 12, which is characterized in that in step 1, sample to be tested and fiber material are added
Enter to extract module (2), controls the first plug (7) for mixed liquor introducing filtering module (3,4) after extracting 30min, keep all plugs
Son is in the open state, after being controlled to a vacuum pump by the nozzle on the third sealing cover and filter 30s, discards and filters out
Filtrate；
If the fiber material can be used as the substance assistant laser desorpted ionization analyte of MALDI, filter residue can be taken off being put into sample
Product collection device, and the ultrapure water that 10-200 μ L is added is dispersed into suspension under ultrasonic wave added；If the fiber material is not
It can be used as the substance assistant laser desorpted ionization analyte of MALDI, then first place filter in filtering module (3,4) groove
Film, and upper filtering module (3) and lower filtering module (4) are snapped together；
Then the eluent of 0.5-3mL is added in filtering module (3,4), ultrasonic wave added 10min passes through the third sealing cover
After the vacuum pump of upper connection filters 30s, filter membrane is discarded；The second plug (9) is finally controlled by Sample introduction sample collection module
(5), it and is added dropwise on the commercialization MALDI target plate being fixed on appliance stand.
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