CN104392886A - Capillary needle, and electro-spray ionization mass spectrometry analytical apparatus and method - Google Patents

Capillary needle, and electro-spray ionization mass spectrometry analytical apparatus and method Download PDF

Info

Publication number
CN104392886A
CN104392886A CN201410523168.0A CN201410523168A CN104392886A CN 104392886 A CN104392886 A CN 104392886A CN 201410523168 A CN201410523168 A CN 201410523168A CN 104392886 A CN104392886 A CN 104392886A
Authority
CN
China
Prior art keywords
sample
nozzle needle
sampling
electron spray
capillary
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201410523168.0A
Other languages
Chinese (zh)
Other versions
CN104392886B (en
Inventor
金迪琼
方群
祝莹
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Zhejiang University ZJU
Original Assignee
Zhejiang University ZJU
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Zhejiang University ZJU filed Critical Zhejiang University ZJU
Priority to CN201410523168.0A priority Critical patent/CN104392886B/en
Priority claimed from CN201410523168.0A external-priority patent/CN104392886B/en
Publication of CN104392886A publication Critical patent/CN104392886A/en
Application granted granted Critical
Publication of CN104392886B publication Critical patent/CN104392886B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/62Investigating 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
    • HELECTRICITY
    • H01BASIC ELECTRIC ELEMENTS
    • H01JELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00Particle spectrometers or separator tubes
    • H01J49/02Details
    • H01J49/04Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
    • HELECTRICITY
    • H01BASIC ELECTRIC ELEMENTS
    • H01JELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00Particle spectrometers or separator tubes
    • H01J49/26Mass spectrometers or separator tubes

Abstract

The invention discloses a capillary needle. The capillary needle comprises a tube body, the two ends of the tube body are respectively provided with an inlet and an outlet for electro-spray, a part of the tube body is bent to form a sampling end, and the sampling end is provided with a sampling port communicating with a cavity in the tube body. The invention also discloses an electro-spray ionization mass spectrometry analytical apparatus applying the capillary needle. The invention also simultaneously discloses a method applying the electro-spray ionization mass spectrometry analytical apparatus for analytical detection. The analytical apparatus is high in integration, compact in structure, easy to control, small in size and low in cost; the sample consumption is greatly reduced, and the experiment cost is decreased; an integrated sample introduction method is employed, and an sample introduction end does not have to be repeatedly placed in a sample and blank solution, such that cross contamination is reduced, and more importantly, the analytical flux is substantially improved; and through combination with an automatic sample changing system, different samples can be automatically introduced, and therefore, the capillary needle, the apparatus and the method are quite suitable for such fields as high-flux screening, unicell analysis, mass spectrum imaging analysis and the like.

Description

A kind of capillary nozzle needle, Electrospray Ionization Mass Spectrometry device and method
Technical field
The invention belongs to mass spectral analysis field, particularly a kind of capillary nozzle needle, with this capillary nozzle needle Electrospray Ionization Mass Spectrometry device and use this device to carry out the method for mass spectral analysis.
Background technology
Utilize electrospray ionization mass spectrum detection technique, direct-detection can be carried out to all kinds of sample molecule without the need to mark, and obtain informative testing result.For the optical detecting method needing to embed fluorescence or develop the color group in sample molecule, electrospray ionization mass spectrum detects can not change the original biologically active of molecule, can avoid the appearance of false positive/negative findings, thus improves Efficiency, reduces research cost.But existing Electrospray Ionization Mass Spectrometry method, not only its sample consumption is at microlitre within the scope of milliliter, and analysis throughput is also well below optical detecting method.
At present, for electrospray ionization mass spectrum high flux sampling and detection technique mainly can be divided into two classes: a class is the automation sampler based on robot; Another kind of, be the microminiaturized analytical equipment of array electron spray nozzle needle based on micro-fluidic chip or droplet array.
The operational mode of Autosampler is generally Flow Injection Analysis pattern, namely utilizes mechanical device to carry out the sampling of automation, sample is injected fluid valve, and by Vavle switching, sample is pumped into electric spray ion source and detect.Because the determined volume of fluid valve limits, the method sample consumption is higher, generally between 1 to 10 microlitre.For reducing sample consumption, Karger seminar utilizes draws the capillary nozzle needle of point directly to draw from porous plate under the effect of negative pressure to receive the sample of upgrading and carry out electron spray detection (Felten, C.; Foret, F.; Minarik, M.; Goetzinger, W.; Karger, B.L.Anal.Chem.2001,73,1449-1454.).Zenobi seminar then utilizes metal sampler pin to dip nano-upgrading sample, and and liquid bridge joint between two capillary gaps touch and carry out sample injection, enter ion source and carry out detecting (Neu, V.; Steiner, R.; M ü ller, S.; Fattinger, C.; Zenobi, R.Anal.Chem.2013,85,4628-4635.).
Owing to having powerful micro-example manipulation ability, microfluidic system has been successfully applied in high flux Electrospray Ionization Mass Spectrometry.Adopt ripe photoetching and micro-processing technology, in monolithic chip, can go out have the array electron spray nozzle needle of good homogeneity by batch making.On chip, each root nozzle needle can both carry out independently sample manipulation and electron spray detection, thus without the need to flushing process, avoids cross pollution possibility, also significantly increases detection flux simultaneously.Such as, Karger seminar is integrated with 96 electron spray nozzle needle arrays in the microfluidic device with 96 passages, can complete detection (Liu, H. to 96 samples in 480 seconds; Felten, C.; Xue, Q.; Zhang, B.; Jedrzejewski, P.; Karger, B.L.; Foret, F.Anal.Chem.2000,72,3303-3310.); Commercialization instrument NanoMate receives the silicon of upgrading electron spray spout array and the Autosampler with disposable pipettor gun head carry out integrated by being integrated with, and achieves to carry out high flux sampling to micro-example and electron spray detects (Kertesz, V.; Van Berkel, G.J.J.Mass Spectrom.2010,45,252-260.).
Liquid drop microfluidic system provides another high-throughout Electrospray Ionization Mass Spectrometry method.Liquid drop microfluidic system utilizes immiscible oil phase to separate drop, and effectively reduce and to merge between the evaporation of micro-volume drop and adjacent drops and the possibility of cross pollution, therefore each drop can be considered an independently microreactor.Compared with the perforated plate sampling of routine or many nozzle needles detection technique, drop microflow control technique significantly can reduce the consumption of sample/reagent.In order to carry out effective electrospray ionization mass spectrum detection to the microlayer model in oil phase, needing to utilize special interface taken out from oil phase by drop and send in the electrospray ionization mass spectrum buffer solution of Continuous Flow, avoiding oil phase to the interference of electro-spray ionization process.For this reason, the seminar at applicant place invents and is a kind ofly integrated with drop formation, drop extracts and integrated chip device (Zhu, the Y. of electron spray function; Fang, Q.Anal.Chem.2010,82,8361-8366.).But because this device can only be used for generation and the detection of identical chemical composition drop, sample is changed comparatively loaded down with trivial details, is difficult to the detection realizing Multi-example, limits its application in high flux screening.
Summary of the invention
The invention provides a kind of capillary nozzle needle, utilize this capillary can realize the fast sampling of testing sample, ensure that the sampling amount of testing sample is reduced to simultaneously and ascend to heaven, practicality is stronger.
Invention also provides and a kind ofly with above-mentioned capillary nozzle needle there is the Electrospray Ionization Mass Spectrometry device of trace and high flux sample ability, electron spray process is utilized to hold the surface tension of hydrophilic surface to the extraction force of liquid in electron spray nozzle needle or sampling, complete the micro liquid sample of fast and reliable, this device can realize the sample solution sampling in conventional 96 or 384 orifice plates, also can sample the micro-drop immersed in oil phase, trace solid or the fluid sample sampling that also can carry out the surface of solids detect.
Invention also provides and a kind ofly utilize above-mentioned Electrospray Ionization Mass Spectrometry device to carry out the method detected, the method is simple to operate, detection efficiency is high, can be used for high-flux medicaments sifting, enzyme dynamics, drug toxicity mensuration, Single cell analysis, intercellular communication thing mensuration and the surface of solids and imaging of tissue etc.
A kind of capillary nozzle needle, comprises body, and these body two ends are inlet and the outlet carrying out electron spray respectively, and a described body part is bent to form sampling end, and this sampling end is provided with the sample tap be communicated with tube cavity body.
In the actual course of processing of described capillary nozzle needle, through bending process in advance by capillary, the end of bending part forms described sampling end, and described sample tap is positioned at the sample end position of capillary, and described inlet, sample tap are connected by the passage in capillary with outlet.
Described capillary is glass or the quartzy or material such as high molecular polymer or metal, and be hollow tubular structure, its cross section is circular or oval or square or trapezoidal or other polygons.The internal diameter (diameter) of described capillary or the interior length of side are 0.1 micron to 1 centimetre, and external diameter (diameter) or the outer length of side are 0.1 micron to 1 centimetre.
The described sampling end being positioned at the bending part of capillary can be circular arc, or square, or V-type, or U-shaped shape, and its processing method can choose high temperature method or Mechanical Method or die methods etc. according to the difference of capillary material.Described sample tap is positioned at the outburst area of sampling end (arc or square or V-type, or U-shaped), and its processing method can choose polishing or etch or laser processing or machining or needle point method etc. according to the difference of capillary material.
For ease of the processing of sample tap, as preferably, described body is U-shaped bending, and described sample tap is located at the bottom outside wall of U-shaped bending.As preferred further, described sample tap outer peripheral edges are the horizontal segment being positioned at same level with sample tap.When adopting this preferred technical scheme, polishing directly can be adopted to grind and to form.
According to the character of sampling sample solution, regioselectivity surface modification is carried out to the capillary surface around sample tap, makes this surface and sample solution have affinity interaction, to improve the stability of sampling.As preferably, described outlet outer wall and sampling end outer wall are through hydrophobicity process; Described horizontal segment is through hydrophily process.The sampling end outer wall of described electron spray needle outlets and sample probe end carries out hydrophobizing surface process; Described hydrophobization process, comprises silanization or the method such as fluothane or polymer coating.
According to the difference of capillary material, choose the structure that existing capillary can be processed into capillary requirement, high-temperature drawn or machining or the method such as laser processing or chemical corrosion can be adopted to process the outlet of described electron spray nozzle needle.As preferably, reduce internal diameter or the external diameter of electron spray needle outlets, improve stability and the sensitivity of electron spray.As preferred further, described sample tap is oval or similar ellipsoidal structure.When adopting this technical scheme, sample tap can adopt polishing to grind self-assembling formation.
A kind of Electrospray Ionization Mass Spectrometry device, the mass spectrometer comprising electron spray nozzle needle, electron spray nozzle needle is provided to the liquid driving device of buffer solution, detect the sample of electron spray nozzle needle ejection, to the sample storing unit of electron spray nozzle needle sampling and high voltage source, described electron spray nozzle needle is the capillary nozzle needle described in above-mentioned arbitrary technical scheme.
The inlet of described electron spray nozzle needle is connected with the liquid driving device that buffer solution is housed, the outlet of described electron spray nozzle needle is placed near mass spectrometric entrance, described sample tap is connected with the sample of sample storing unit, one pole of described high voltage source is connected with the outlet of the inlet of electron spray nozzle needle or electron spray nozzle needle, and an other pole is connected with mass spectrometric entrance.
As preferably, described electron spray nozzle needle is multiple, and in one dimension or two-dimensional arrangement form capillary array.Adopt the program can realize Multi-example sampling and mass spectral analysis.
As preferably, described sample storing unit comprises: for holding microchip or the porous plate of sample to be analyzed; System is changed to the sample that microchip or porous plate move in real time or change.Described porous plate can adopt existing 96 or 384 orifice plates; System changed by described sample can adopt the conveying mechanism etc. automatically controlling to realize three-dimensional displacement, such as, can adopt the three-dimensional working platform of displacement on the realized three-dimensional realized by screw pair structure.
Utilize the above-mentioned Electrospray Ionization Mass Spectrometry device of right to carry out the method detected, comprising:
Step one: start liquid drive unit, the inlet of electron spray buffer solution from electron spray nozzle needle is injected continuously, through sampling end and sample tap, arrives the outlet of electron spray nozzle needle, and start high voltage source, electron spray buffer solution is sprayed by the outlet of electron spray nozzle needle and forms stable electron spray;
Step 2: make the sample contacts in the sample tap of the sampling end of electron spray nozzle needle and sample storing unit, then both are separated, utilize electron spray process to the swabbing action of liquid in electron spray nozzle needle or sample in the surface tension of sample tap, sample is sampled in introducing electron spray nozzle needle passage by sample tap;
Step 3: keep the sampling end of electron spray nozzle needle and the disengaged position of sample, make to enter sample in electron spray nozzle needle passage under the driving of electron spray buffer solution, outlet via electron spray nozzle needle sprays, and ionization under the effect of electric field, enters mass spectrometer analysis.For fluid sample, by the size regulating the buffer solution optional surface modification's area injected around flow velocity, electron spray voltage, the time of contact sampling end and sample and sample tap to regulate sampling amount.For solid sample, inject flow velocity, electron spray voltage by regulating buffer solution, sample the size of holding and regulating sampling amount with the time of contact of sample, the size of sample tap, the solvent composition of buffer solution.
Repeat above step, complete sampling and the analysis of different sample or same sample diverse location.
In the present invention, described sample to be analyzed can be fluid sample or solid sample or liquid-solid mixture sample.
Sampling end and sample tap, in the sampling interval process of carrying out different sample or same sample diverse location, are immersed in cleaning fluid the cleaning carrying out sampling end and sample tap, reduce the cross pollution between different sample by the present invention.
In order to prevent the liquid evaporation problems in sampling process, sample covers one deck and the immiscible liquid of this solution as protective layer.When sample to be analyzed is inorganic matter sample, as preferably, described sample surfaces is covered with oil phase layer.
In the present invention, the difference of single sampling amount state of matter is per sample different, and for fluid sample, sampling volume scope 1 receives and rise to 1 milliliter; For solid sample, sample size scope 0.1 flies gram to 1 gram.
Major advantage of the present invention is: (1) analytical equipment material is simple and easy to get, integration degree is high, compact conformation, be easy to manipulation, volume is little, cost is low; (2) both may be used for the sample feeding analysis of porous plate, the medium conventional-volume of PCR pipe, and sample introduction and the surface analysis of submicrosample can have been carried out again, greatly reduce sample consumption, save experimental cost; (3) sample injection method of integration, sample introduction end does not need repeatedly to be placed in sample and blank solution, reduces cross pollution, the more important thing is and significantly improve analysis throughput; (4) vary system in conjunction with automation, can realize introducing the automation of various sample, be applicable to very much in the fields such as high flux screening, single cell analysis, mass spectrum imaging analysis.
Accompanying drawing explanation
Fig. 1 is the schematic diagram for the Electrospray Ionization Mass Spectrometry device of droplet sample sampling under oil with trace and high flux sample ability of embodiment 1.
Fig. 1 a is the schematic enlarged-scale view of part A in Fig. 1.
Fig. 2 is the Electrospray Ionization Mass Spectrometry device schematic diagram for fluid sample sampling in porous plate with trace and high flux sample ability of embodiment 3.
Fig. 3 is the mass signal figure of acetylcholinesterase (AchE) the inhibitor screening experiment products therefrom choline of embodiment 1.
Fig. 4 is the calibration curve of relation between the choline concentration of embodiment 2 and mass signal intensity.
Fig. 5 is the enzyme level curve of three kinds of effective AchE inhibitor of embodiment 2.
Fig. 6 is the mass signal figure reserpine sample solution in 96 orifice plates with same concentrations being carried out to sample analysis of embodiment 3.
Fig. 7 is mass signal figure sample different in 96 orifice plates being carried out to sample analysis of embodiment 3.
In above-mentioned accompanying drawing, 1-inlet, 2-samples end, 3-sample tap, 3a-horizontal segment, the outlet of 4-electron spray nozzle needle, 5-liquid driving device, system changed by 6-sample, 7-high voltage source, 8-mass spectrometer, 9-sample, 10-capillary nozzle needle, 11-electron spray buffer solution, 12-microchip, 13-oil phase layer, 14-porous plate, 15-service sink.
Embodiment
Below in conjunction with specific embodiment, technical scheme of the present invention is described further, but protection scope of the present invention is not limited thereto.
With reference to accompanying drawing, below will describe in detail according to a preferred embodiment of the invention.
Embodiment 1
Fig. 1 is the Electrospray Ionization Mass Spectrometry device schematic diagram for droplet sample sampling under oil with trace and high flux sample ability set up according to the present invention.This device is integrated with inlet 1, sampling end 2 and sample tap 3 by one and exports the capillary nozzle needle 10 of 4, a set of liquid driving device 5, and system 6 changed by a set of moveable sample, and a set of high voltage source 7 and a mass spectrometer 8 form.In Fig. 1, arrow represents the buffer solution direction of motion.
Capillary nozzle needle 10 is processed by capillary, comprises body, and these body two ends are inlet 1 and the outlet 2 of buffer solution respectively, and a body part is U-shaped is bent to form sampling end 2, and this sampling end is provided with and is communicated with sample tap 3 with tube cavity body.Sample tap 3 is located at the bottom outside wall of U-shaped bending.Export 2 place's horizontal bucklings.Sample tap 3 outer peripheral edges are the horizontal segment 3a being positioned at same level with sample tap 3.
The material of capillary nozzle needle 10 is fused silica glass, cross section is circular, internal diameter is 100 microns, external diameter is 365 microns, its concrete procedure of processing is as follows: (1) carries out stretch processing by flame heating to capillary, obtain the electron spray needle outlets 4 drawing point, its internal diameter is 50 microns; (2) by flame heating, bending process is carried out to capillary, obtain U-shaped sample end 2, and make the outlet 4 of electron spray nozzle needle be orthogonal state with the liquid inlet 1 of buffering; (3) silanization treatment is carried out to capillary outer wall, make it have hydrophobicity; (4) sample tap 3 is obtained by carrying out grinding to the top of sample end 2 outburst area, sample tap 3 is oval, long diameter 200 microns, short diameter 100 microns, the horizontal segment 3a that the grinding of sample tap 3 surrounding is formed is for having hydrophilic hydrophilic circle, can effectively prevent oil phase from entering capillary nozzle needle 10 by sample tap 3 inner, as Fig. 1 a.
The concrete using method of embodiment 1 device is as follows: (1) start liquid drive unit 5, the inlet 1 of electron spray buffer solution 11 from capillary nozzle needle 10 is injected continuously, through sampling end 2 and sample tap 3, arrive the outlet 4 of electron spray nozzle needle, and start high voltage source 7, electron spray buffer solution is sprayed by the outlet 4 of capillary nozzle needle 10 and forms stable electron spray; (2) sample 9 solution to be analyzed is retained in the form of drop to be had on the microchip 12 of hydrophilic pores array, droplet array is coated with the oil phase layer 13 immiscible with sample 9, for preventing the material exchange between drop evaporation and drop; (3) microchip 12 is placed in sample replacing system 6, the movement of system 6 in x, y and z axes three dimensions is changed by sample, sample 9 drop and oil reservoir is departed from after making the sample tap 3 of the sampling end 2 of capillary nozzle needle 10 and sample 9 drop contact certain hour, to utilize in electron spray process the swabbing action of liquid in capillary nozzle needle 10 or sample 9 solution in the surface tension of sample tap, sample 9 is introduced in capillary nozzle needle 10 passage by sample tap 3; Sample is changed system 6 and is generally three-dimensional movement platform structure; (4) disengaged position of capillary sampling end 2 and sample tap 3 and sample 9 drop and oil reservoir is kept, make to enter sample 9 solution in capillary channel under the driving of electron spray buffer solution, electron spray needle outlets 4 via capillary nozzle needle 10 sprays, ionization under the effect of electric field, enters mass spectrometer 8 and analyzes; (5) repeat the step of above (2) (3) (4), complete sampling and the analysis of different sample 9 drop.
Fig. 3 is according to above-mentioned sampling analysis device and using method thereof, carries out sampling and analysing to sample drop under 128 oil, for screening the mass signal figure of acetylcholinesterase (AchE) inhibitor.
Concrete, its buffer solution is 30% methyl alcohol 1% acetic acid solution; Each analyzed drop in droplet array on microchip 12 comprises three kinds of reactants, substrate---acetylcholine (Ach), enzyme catalyst---acetylcholinesterase (AchE), compound to be screened---the compound of 3 kinds of known AchE inhibitor and 27 kinds of Stochastic choice, product choline (m/z 104.5) is as mass spectrographic determinand; The volume of each drop is 300 receive liter; Oil phase layer 13 is the mineral oil of 400 microlitres; Buffer flow rate is 1 mul/min, and voltage is 2.7 kilovolts, and sampling end 2 is 1 second with the time of contact of sample 9 drop.
128 drops comprise a positive control group (not containing inhibitor, be numbered No. 0), 30 contain different compound but same substrate and screening of catalyst group (being numbered No. 1-30), and a negative control group is not (containing substrate, be numbered No. 31), every 4 drops are one group, often organize the Compound Phase used in drop same.Wherein, compound used in No. 1-3 each group is known inhibitor, and compound used in No. 4-30 each group is the material of random choose.Because the classes of compounds in difference group drop is different, different to the suppression degree of enzyme reaction, the product assay therefore in different drop is different.In No. 1-3, the signal of choline is lower, illustrates that these three kinds of compounds have enzyme inhibition to AchE.In same group, the mass signal of 4 drops is relatively consistent.
The present embodiment proves that this device is applicable to the medicament high flux screening of micro-reaction system.
Embodiment 2
Fig. 4 is sampling analysis device and the using method thereof of according to a preferred embodiment of the invention 1, take choline as sample, by detecting the mass signal with drop under the oil of various biliary alkali concn, obtain the calibration curve of relation between choline concentration and mass signal intensity in the lower drop of oil.
Concrete, courage paper mill wastewater is respectively 0.2mM (mmol/L), 0.4mM, 1.0mM, 2.5mM, 5.0mM, 8mM and 10.0mM, and droplet size is 300 and receives liter, and the drop number of each concentration is 8.Obtain the standard curve I=3632C+1694 (R between the corresponding mass signal intensity of choline concentration 2=0.999).According to this calibration curve, calculate the choline concentration in different drop by mass signal.
Fig. 5 is the analytical equipment utilizing preferred embodiment 1, and the calibration curve of Fig. 4, the enzyme level curve of the three kinds of effective inhibitor of AchE obtained.
Concrete, under three kinds of effective AchE inhibitor being carried out respectively to the oil of enzyme reaction product content of choline under variable concentrations inhibitor, drop sample analysis detects, and inhibitor concentration is respectively 0.01nM (nmol/L), 0.1nM, 1nM, 10nM, 100nM, 1 μM, 10 μMs, 100 μMs, 1mM and 10mM, droplet size is 300 and receives liter, and the drop number under each concentration is 4.Gained choline mass signal intensity obtains the content of choline under each inhibitor concentration according to above-mentioned standard curve I=3632C+1694 conversion, get the negative log value of inhibitor concentration, obtain neostigmine respectively, rise happiness dragon and the enzyme inhibitor curve corresponding to eserine, calculate its half inhibitory enzyme concentration according to S shape approximating method and be respectively 69 ± 19nM, 26 ± 3.7 μMs and 61 ± 17nM.
Utilize the method in the present embodiment to calculate neostigmine, rise happiness dragon consistent with its normal data with half inhibitory enzyme concentration of the enzyme inhibitor corresponding to eserine, the present embodiment proves that this device can carry out quantitative analysis to sample, has reliable drug screening ability.
Embodiment 3
Fig. 2 is the analytical equipment schematic diagram of embodiment 3.Adopt the capillary sampler of similar embodiment 1, sampling and analysing is carried out to sample 9 solution in porous plate 14.In the present embodiment, processing method of capillary tube is identical with embodiment 1.Porous plate 14 adopts commercial 96 orifice plates.
Described in embodiment 3, the concrete using method of analytical equipment is as follows: (1) start liquid drive unit 5, the buffer solution inlet 1 of electron spray buffer solution from capillary nozzle needle 10 is injected continuously, through sampling end 2 and sample tap 3, arrive electron spray needle outlets 4, and start high voltage source 7, buffer solution is sprayed by electron spray needle outlets 4 and forms stable electron spray; (2) sample 9 solution storage to be analyzed is in porous plate 14; (3) porous plate 14 is placed in sample replacing system 6, the movement of system 6 in x, y and z axes three dimensions is changed by sample, the sample tap 3 making capillary sample end contacts with sample 9 solution, and then mobile example changes system 6, make capillary sample end 2 and sample tap 3 and sample 9 solution to depart from, to utilize in electron spray process the swabbing action of liquid in capillary or sample 9 solution in the surface tension of sample tap, sample is introduced in capillary channel by sample tap 3; (4) disengaged position of capillary sampling end 2 and sample tap 3 and sample 9 solution is kept, make sample 9 solution entering capillary channel under the driving of electron spray buffer solution, electron spray needle outlets 4 via capillary nozzle needle 10 sprays, ionization under the effect of electric field, enters mass spectrometer 8 and analyzes; (5) mobile example changes system 6, capillary sampling end 2 and sample tap 3 immersion are stored in the service sink 15 of cleaning fluid clean, then mobile example changes system 6, make capillary sample end 2 and sample tap 3 and cleaning fluid to depart from, and keep disengaged position certain hour, until remain without cleaning fluid outside capillary sampling end 2 and sample tap 3; (6) repeat the step of above (2) (3) (4) (5), complete sampling and the analysis of sample 9 liquid in the different hole of porous plate.
Concrete, its buffer solution is 30% methyl alcohol 1% acetic acid solution; Sample solution is concentration 1.0 × 10 -6reserpine (m/z 609.5) solution of mol/L, the liquor capacity in each hole is 30 microlitres; Cleaning fluid is 30% methyl alcohol 1% acetic acid solution; Buffer flow rate is 1 mul/min, and voltage is 2.7 kilovolts, and the sample tap 3 of sampling end is 1 second with the time of contact of sample 9 drop, and sampling end 2 is 5 seconds with the scavenging period of sample tap 3.
Fig. 6 is according to above-mentioned sampling analysis device and using method thereof, carries out the mass signal figure of sample analysis to the reserpine solution of same concentrations in 96 orifice plates.The detection signal in each hole be one unimodal, the relative standard deviation of 96 signal peak heights is 11.4%, and sampling detection time of average each sample is 31.3 seconds.
Fig. 7 is according to above-mentioned sampling analysis device and using method thereof, 8 kinds of samples in 96 orifice plates is carried out to the mass signal figure of sample analysis.8 kinds of samples are respectively a-caffeine, b-angiotensin I, c-angiotensin II, d-reserpine, e-deserpidine, f-5-methoxysulfadiazine, g-people's Tyrosinase (243-251) and h-cycocel, 12 holes filled by per sample (p.s.), totally 96 holes, the detection signal in each hole be one unimodal.With 8 kinds of each Kong Weiyi row of sample, totally 12 row, detect by row during detection, have namely detected first row and have detected secondary series, until detected the 12nd row.The relative standard deviation of each mass signal peak value of these 8 kinds of samples is respectively 2.9%, 6.1%, 15.6%, 7.5%, 10.7%, 5.0%, 5.0% and 6.6%, all in the relative standard deviation allowed band of existing Mass Spectrometer Method; Sampling detection time of average each sample is 34.3 seconds.
The present embodiment result shows that the sampling detection of this system to fluid sample in porous plate has good stability and reappearance, and higher detection flux.

Claims (10)

1. a capillary nozzle needle, comprise body, these body two ends are inlet (1) and the outlet (2) carrying out electron spray respectively, it is characterized in that, a described body part is bent to form sampling end (2), and this sampling end is provided with the sample tap (3) be communicated with tube cavity body.
2. capillary nozzle needle according to claim 1, is characterized in that, described sample tap (3) is located at the bottom outside wall of sampling end (2) bending part.
3. capillary nozzle needle according to claim 2, is characterized in that, described sample tap (3) outer peripheral edges are the horizontal segment (3a) being positioned at same level with sample tap (3).
4. capillary nozzle needle according to claim 3, is characterized in that, described outlet (2) outer wall and described sampling end (2) outer wall are through hydrophobicity process; Described horizontal segment (3a) is through hydrophily process.
5. capillary nozzle needle according to claim 1, is characterized in that, described sample tap (3) is oval or similar ellipsoidal structure.
6. an Electrospray Ionization Mass Spectrometry device, the mass spectrometer (8) comprising electron spray nozzle needle, electron spray nozzle needle is provided to the liquid driving device of buffer solution (5), the sample of electron spray nozzle needle ejection is detected, to the sample storing unit of electron spray nozzle needle sampling and high voltage source (7), it is characterized in that, described electron spray nozzle needle is the capillary nozzle needle (10) described in the arbitrary claim of claim 1-5.
7. Electrospray Ionization Mass Spectrometry device according to claim 6, is characterized in that, described capillary nozzle needle (10) for multiple, and is that one dimension or two-dimensional arrangement form capillary array.
8. the Electrospray Ionization Mass Spectrometry device according to claim 6 or 7, is characterized in that, described sample storing unit comprises:
For holding microchip (12) or the porous plate (14) of sample to be analyzed (9);
System (6) is changed to the sample that microchip (12) or porous plate (14) move in real time or change.
9. utilize the Electrospray Ionization Mass Spectrometry device described in the arbitrary claim of claim 6-8 to carry out the method detected, comprising:
Step one: start liquid drive unit (5), the inlet (1) of electron spray buffer solution from capillary nozzle needle (10) is injected continuously, through sampling end (2) and sample tap (3), arrive the outlet (4) of capillary nozzle needle (10), and start high voltage source (7), electron spray buffer solution is sprayed by the outlet (4) of capillary nozzle needle (10) and forms stable electron spray;
Step 2: the sample tap of capillary nozzle needle (10) (3) is contacted with the sample (9) in sample storing unit, then both are separated, utilize electron spray process to the swabbing action of liquid in capillary nozzle needle (10) or sample (9) surface tension in sample tap (3), sample (9) is sampled in introducing capillary nozzle needle (10) passage by sample tap (3);
Step 3: keep the sampling end (2) of capillary nozzle needle (10) and the disengaged position of sample (9), make to enter sample (9) in capillary nozzle needle (10) passage under the driving of electron spray buffer solution, outlet (4) via capillary nozzle needle (10) sprays, ionization under the effect of electric field, enters mass spectrometer (8) and analyzes.
10. Electrospray Ionization Mass Spectrometry detection method according to claim 9, is characterized in that, described sample (9) surface is covered with immiscible fluid protection layer.
CN201410523168.0A 2014-09-30 A kind of capillary tube nozzle needle, Electrospray Ionization Mass Spectrometry device and method Active CN104392886B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201410523168.0A CN104392886B (en) 2014-09-30 A kind of capillary tube nozzle needle, Electrospray Ionization Mass Spectrometry device and method

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201410523168.0A CN104392886B (en) 2014-09-30 A kind of capillary tube nozzle needle, Electrospray Ionization Mass Spectrometry device and method

Publications (2)

Publication Number Publication Date
CN104392886A true CN104392886A (en) 2015-03-04
CN104392886B CN104392886B (en) 2017-01-04

Family

ID=

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104776384A (en) * 2015-04-29 2015-07-15 青岛康源聚力生物科技有限公司 Electrostatic spraying streetlamp device capable of eliminating PM2.5 (Particulate Matter 2.5)
CN105181784A (en) * 2015-08-20 2015-12-23 中国检验检疫科学研究院 Method for rapidly screening 40 prohibited antibiotics in cosmetics
CN105632875A (en) * 2016-01-27 2016-06-01 浙江大学 Deabsorption ionization mass spectrum interface used for high-resolution imaging of mass spectrum
CN108780063A (en) * 2016-03-09 2018-11-09 株式会社岛津制作所 The analysis method of the Biosample of quality analysis apparatus and the use device
WO2020114344A1 (en) * 2018-12-05 2020-06-11 浙江大学 Chromatographic analysis device employing multi-function integrated probe, and use method
CN111965093A (en) * 2020-10-26 2020-11-20 宁波华仪宁创智能科技有限公司 Single cell mass spectrometry device and method

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1321327A (en) * 1998-06-09 2001-11-07 杜邦药物研究实验室股份有限公司 Parallel fluid electrospray mass spectrometer
CN1975413A (en) * 2005-11-16 2007-06-06 安捷伦科技有限公司 Reference mass introduction via a capillary
CN101060932A (en) * 2004-11-22 2007-10-24 霍夫曼-拉罗奇有限公司 Bent microfluidic device
US7303727B1 (en) * 2002-03-06 2007-12-04 Caliper Life Sciences, Inc Microfluidic sample delivery devices, systems, and methods
US20080315083A1 (en) * 2004-02-05 2008-12-25 Dieter Lubda Device and Method for Coupling Capillary Separation Methods and Mass Spectrometry
US20110220784A1 (en) * 2010-03-11 2011-09-15 Battelle Memorial Institute Focused analyte spray emission apparatus and process for mass spectrometric analysis

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1321327A (en) * 1998-06-09 2001-11-07 杜邦药物研究实验室股份有限公司 Parallel fluid electrospray mass spectrometer
US7303727B1 (en) * 2002-03-06 2007-12-04 Caliper Life Sciences, Inc Microfluidic sample delivery devices, systems, and methods
US20080315083A1 (en) * 2004-02-05 2008-12-25 Dieter Lubda Device and Method for Coupling Capillary Separation Methods and Mass Spectrometry
CN101060932A (en) * 2004-11-22 2007-10-24 霍夫曼-拉罗奇有限公司 Bent microfluidic device
CN1975413A (en) * 2005-11-16 2007-06-06 安捷伦科技有限公司 Reference mass introduction via a capillary
US20110220784A1 (en) * 2010-03-11 2011-09-15 Battelle Memorial Institute Focused analyte spray emission apparatus and process for mass spectrometric analysis

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
HANGHUI LIU ET AL: "Development of Multichannel Device with an Array of Electrospray Tips for High-Throughput Mass Spectrometry", 《ANALYTICAL CHEMISTRY》 *
HELENE BONKERUD DUGSTAD ET AL: "Development and characterization of a small electromembrane extraction probe coupled with mass spectrometry for real-time and online monitoring of in vitro drug metabolism", 《ANALYTICAL AND BIONANLYTICAL CHEMISTRY》 *
祝莹: "基于微流控液滴系统的质谱和色谱分析方法的研究", 《中国博士学位论文全文数据库(工程科技I辑)》 *

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104776384A (en) * 2015-04-29 2015-07-15 青岛康源聚力生物科技有限公司 Electrostatic spraying streetlamp device capable of eliminating PM2.5 (Particulate Matter 2.5)
CN104776384B (en) * 2015-04-29 2017-04-12 青岛康源聚力生物科技有限公司 Electrostatic spraying streetlamp device capable of eliminating PM2.5 (Particulate Matter 2.5)
CN105181784A (en) * 2015-08-20 2015-12-23 中国检验检疫科学研究院 Method for rapidly screening 40 prohibited antibiotics in cosmetics
CN105632875A (en) * 2016-01-27 2016-06-01 浙江大学 Deabsorption ionization mass spectrum interface used for high-resolution imaging of mass spectrum
CN108780063A (en) * 2016-03-09 2018-11-09 株式会社岛津制作所 The analysis method of the Biosample of quality analysis apparatus and the use device
CN108780063B (en) * 2016-03-09 2021-02-26 株式会社岛津制作所 Mass spectrometer and method for analyzing biological sample using same
WO2020114344A1 (en) * 2018-12-05 2020-06-11 浙江大学 Chromatographic analysis device employing multi-function integrated probe, and use method
CN111272887A (en) * 2018-12-05 2020-06-12 浙江大学 Chromatographic analysis device based on multifunctional integrated probe and use method
CN111272887B (en) * 2018-12-05 2021-04-20 浙江大学 Chromatographic analysis device based on multifunctional integrated probe and use method
CN111965093A (en) * 2020-10-26 2020-11-20 宁波华仪宁创智能科技有限公司 Single cell mass spectrometry device and method
CN111965093B (en) * 2020-10-26 2021-02-05 宁波华仪宁创智能科技有限公司 Single cell mass spectrometry device and method

Similar Documents

Publication Publication Date Title
US20180078933A1 (en) Injection of multiple volumes into or out of droplets
EP3473905B1 (en) System and method for performing droplet inflation
US9120096B2 (en) Manipulating the size of liquid droplets in digital microfluidics
Kaigala et al. A vertical microfluidic probe
Petersen et al. Electromembrane extraction from biological fluids
CA2740113C (en) Hybrid digital and channel microfluidic devices and methods of use thereof
Tice et al. Formation of droplets and mixing in multiphase microfluidics at low values of the Reynolds and the capillary numbers
US8742338B2 (en) Systems and methods for laser assisted sample transfer to solution for chemical analysis
US6423966B2 (en) Method and apparatus for maldi analysis
Feng et al. Advances in coupling microfluidic chips to mass spectrometry
Fair Digital microfluidics: is a true lab-on-a-chip possible?
US6918309B2 (en) Sample deposition method and system
Gelpí Interfaces for coupled liquid‐phase separation/mass spectrometry techniques. An update on recent developments
AU744879B2 (en) Apparatus and method for transferring liquids
EP1866408B1 (en) Electrosonic cell manipulation device and method of use thereof
JP4142280B2 (en) Apparatus for fluid analysis and controlled transport of fluids
US6231737B1 (en) Material transport method and apparatus
Kameoka et al. An electrospray ionization source for integration with microfluidics
Gao et al. Recent advances in microfluidics combined with mass spectrometry: technologies and applications
AU2002307529B2 (en) Hollow fiber membrane sample preparation devices
Wang et al. Microfluidics-to-mass spectrometry: a review of coupling methods and applications
Shui et al. Scalable attoliter monodisperse droplet formation using multiphase nano-microfluidics
US8231844B2 (en) Method and device for manipulating liquids in microfluidic systems
EP2200740B1 (en) Microfluidic methods
Licklider et al. A micromachined chip-based electrospray source for mass spectrometry

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant