WO2002055990A9 - Processus de microfabrication pour emetteurs de spectrometrie de masse en mode electronebulisation (electrospray) - Google Patents

Processus de microfabrication pour emetteurs de spectrometrie de masse en mode electronebulisation (electrospray)

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Publication number
WO2002055990A9
WO2002055990A9 PCT/US2002/000705 US0200705W WO02055990A9 WO 2002055990 A9 WO2002055990 A9 WO 2002055990A9 US 0200705 W US0200705 W US 0200705W WO 02055990 A9 WO02055990 A9 WO 02055990A9
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WO
WIPO (PCT)
Prior art keywords
electrospray
pdms
emitter
wafer
layer
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Application number
PCT/US2002/000705
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English (en)
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WO2002055990A8 (fr
WO2002055990A2 (fr
WO2002055990A3 (fr
Inventor
Daniel R Knapp
Jin-Sung Kim
Original Assignee
Music Foundation For Res Dev
Daniel R Knapp
Jin-Sung Kim
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Application filed by Music Foundation For Res Dev, Daniel R Knapp, Jin-Sung Kim filed Critical Music Foundation For Res Dev
Priority to AU2002243506A priority Critical patent/AU2002243506A1/en
Publication of WO2002055990A2 publication Critical patent/WO2002055990A2/fr
Publication of WO2002055990A3 publication Critical patent/WO2002055990A3/fr
Publication of WO2002055990A9 publication Critical patent/WO2002055990A9/fr
Publication of WO2002055990A8 publication Critical patent/WO2002055990A8/fr

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/62—Detectors specially adapted therefor
    • G01N30/72—Mass spectrometers
    • G01N30/7233—Mass spectrometers interfaced to liquid or supercritical fluid chromatograph
    • G01N30/724—Nebulising, aerosol formation or ionisation
    • G01N30/7266—Nebulising, aerosol formation or ionisation by electric field, e.g. electrospray
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/0013—Miniaturised spectrometers, e.g. having smaller than usual scale, integrated conventional components
    • H01J49/0018—Microminiaturised spectrometers, e.g. chip-integrated devices, Micro-Electro-Mechanical Systems [MEMS]
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/10—Ion sources; Ion guns
    • H01J49/16—Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
    • H01J49/165—Electrospray ionisation
    • H01J49/167—Capillaries and nozzles specially adapted therefor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/60—Construction of the column
    • G01N30/6004—Construction of the column end pieces
    • G01N2030/6013—Construction of the column end pieces interfaces to detectors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/60—Construction of the column
    • G01N30/6095—Micromachined or nanomachined, e.g. micro- or nanosize

Definitions

  • Microfluidic analytical systems have been a subject of increasing interest in recent years, particularly for the analysis of biomolecules.
  • Devices have been reported using high performance liquid chromatography, electrophoresis, isoelectric focusing, and electrochromatography separations with photometric, fluorometric, electrochemical, and mass spectrometric (MS) detection methods.
  • MS detection has been focused upon electrospray ionization (ESI), and several groups have reported the development of microfluidic systems for interfacing to ESI-MS.
  • ESI electrospray ionization
  • microfabricated ESI sources as an integral part of the device.
  • One research group developed silicon nitride and parylene electrospray emitters microfabricated on silicon devices.
  • An ESI emitter for an isoelectric focusing device has been constructed on polycarbonate plates using laser micromachining method.
  • electrospray nozzles have been fabricated from a monolithic silicon substrate.
  • microfabricated ESI devices gave good electrospray performance, but all of them require relatively complex processes and facilities to produce the devices.
  • a goal is to produce a microfluidic device for ESI-MS analysis, such as the analysis of peptides and proteins.
  • Another object is to produce inexpensive, disposable devices for high throughput proteomics work.
  • Such devices ideally include the electrospray emitter as an integral part fabricated by the same process as the device itself.
  • Microfabricated emitters for electrospray ionization mass spectrometry are produced using a soft lithography process.
  • a substrate is coated with a photo resist material.
  • a photo mask is positioned over the photo resist material.
  • the photo mask selectively permits, or prevents, exposure of the photo resist material to radiation.
  • the resulting wafer is developed so that the portion of the photo resist that was not exposed to radiation is removed, and the wafer forms a mold.
  • a suitable material such as polydimethylsiloxane (PDMS), is prepared as a two-part material, and is then poured over the wafer, which acts as a mold, to form one layer of the emitter.
  • PDMS polydimethylsiloxane
  • the adjoining layer may be similarly formed, with the top layer and bottom layer joined, such as by the application of oxygen plasma.
  • the substrate may be coated with a second layer of photo resist material, after radiation exposure of the first layer, but prior to development of the first layer, so as to provide more complex shape.
  • the emitters are formed as electrospray tips along a thin membrane on the edge of the device, which communicate with small channels that are formed in the device by the soft lithography process.
  • the process yields a device having small channels with relatively sharp angles at the emitter tip.
  • the sharp points give higher field strength in electrospray applications, and permit operation at lower voltages, while retarding the formation of undesired droplets at the tip.
  • the process provides a microfabrication method for ESI emitters of microfluidic devices, without the need for manual attachment of separate components.
  • Single channel and multiple channel emitters are formed along a thin membrane on the edge of a device comprising two bonded parts. These devices may be interfaced to an ESI time-of-flight (TOF) MS.
  • TOF time-of-flight
  • Figure 1 is a photomask for a top portion of a four channel device.
  • Figure 2A is side view of the molding of the device on the master wafer substrate with a photoresist pattern.
  • Figure 2B is an isolation of a portion of Figure 2A detailing the formation of the thin tip for the emitter.
  • Figure 2C is an isolated perspective view of the emitter, showing the angles of the emitter tip and the dimensions of the channel.
  • Figure 3 depicts photomasks for the bottom (A) and top (B) photoresist layers for the two layer method.
  • Figure 4A is a perspective view of the two layer photoresist process.
  • Figure 4B is an elevation showing the casting of the PDMS using the two layer photoresist process.
  • Figure 5A shows a photomask for the photoresist patterns of the emitter tips.
  • Figure 5B shows a photomask for the photoresist patterns of the channels.
  • Figure 6 demonstrates the steps of the resin casting method.
  • Figure 7 demonstrates the operation of the PDMS multichannel device interfaced to ESI-TOF-MS with sample injection system and ESI voltage connection.
  • Figure 8A is a photomicrograph showing a sample solution droplet on the hydrophobic surface of the emitter without ESI voltage.
  • Figure 8B is a photomicrograph of the electrospray.
  • Figure 9A is a graph showing the signal stabilities
  • Figure 9B is a graph showing the TIC of the sample concentration of 1 ⁇ M peptide mixture.
  • Figure 9C is a graph showing the TIC.
  • Figures 10A and 10B are graphs showing the spectra for the sample mixture of angiotensin I [a] and bradykinin [b].
  • Figure 11 is a graph showing the spectrum for the sample concentration flow.
  • microfluidic devices of glass, silicon or quartz substrates utilize methods for channel production originally developed from microelectronic fabrication, soft lithography provides a simpler microfabrication process and requires less sophisticated production facilities.
  • the photoresist patterns for the microfluidic channels produced on silicon wafers by photolithography are used as masters to mold polydimethylsiloxane (PDMS) replicas as grooves in a PDMS surface.
  • PDMS polydimethylsiloxane
  • the PDMS substrate has several advantages for microfluidic devices including low cost, favorable optical properties for photometric or fluorometric detection, and a rapid and simple fabrication process using soft lithography.
  • the microfluidic devices made by this method are also readily transferable to injection molding processes for larger scale production of the devices.
  • the photomask design for the microfluidic channels of the device may be created with a CAD program, and printed on transparency film using a high- resolution image printer, such as a 3556 dpi resolution setter.
  • Figure 1 shows the photomask image 2 for the top PDMS part of the four channel device. This transparency was used as a mask in contact photolithography to produce masters composed of a positive relief of negative photoresist on a silicon wafer substrate. After radiation exposure and developing, the white areas of the mask yield raised areas on the wafer with negative photoresist.
  • the design defines the channels and edge profile of the PDMS device with each channel terminating at a point on the edge.
  • the channels 3, shown by white lines in Figure 1 are designed to a desired width and depth.
  • the channels have a width of 100 ⁇ m, a depth of 30 ⁇ m, and a length 4 of 4 cm. The depth is obtained by coating the photoresist on the wafer substrate to 30 ⁇ m.
  • the photomask of Figure 1 depicts four channels, but more, or fewer, channels can be formed by the configuration of the photomask.
  • a substrate 6 which may be a 100 mm silicon wafer, cleanroom grade. Moisture may be removed by heating the substrate on a hot plate at 100 °C for 2 hours to remove surface moisture.
  • Negative photoresist such as SU-8 50 (Microchemical Corp., Newton, MA) is coated on the wafer. For example, the photoresist 8 coating may be applied using a spin coater spun at 5000 rpm, following acceleration at 1000 rpm seconds -1 , for a total spin time of 25 seconds (including acceleration time). The coated wafer may cured by baking, such as by baking at 55 °C for 3 minutes, and then at 95 °C for 25 minutes.
  • the photomask image shown in Figure 1 is exposed to radiation that is suitable to the particular photo resist, and patterned on the negative photoresist to expose the wafer.
  • An ultraviolet (UV) lamp may provide radiation exposure to the SU-8 50 photoresist, and the wafer is exposed as required, such as for 30 seconds.
  • the wafer exposed with UV is baked at 95 °C for 15 minutes, and developed in a developer that is appropriate to the photoresist, which for SU-8 50 is 2-(1-methoxy)propyl acetate. After developing the wafer, the height of photoresist pattern on the master wafer is verified.
  • the photoresist pattern on the master wafer is surrounded by a barrier or dam 10, which may be formed by brass bars.
  • the thin membrane for the PDMS emitters is made by covering the ends of the tips 12 on the photoresist pattern (the right side of Figure 2A and 2B) with a material or device having the desired arcuate surface 14, such as an appropriately formed transparency film.
  • a PDMS prepolymer, such as SILGARD 184 (Dow Corning) is mixed with a curing agent in a ratio of 10:1 , and the premixture is degassed under vacuum for 1 hour.
  • FSCs fused-silica capillaries 16
  • the degassed premixture is cast against the master wafer which is silanized with (tridecafluoro-1 ,1 ,2,2-tetrahydrooctyi)-1-trichlorosilane under vacuum for 2 hours.
  • the premixture on the master wafer is cured by heating, such as at 70°C for 3 hours in an oven, and the cured top PDMS part was peeled from the master wafer.
  • the FCSs in the top PDMS part are removed and replaced with longer segments of the same cross sectional dimension FSCs to make fluid connections to the channels.
  • the new FSCs are attached while flowing nitrogen through the capillary to prevent clogging, and the FSCs are secured in the place with PDMS premixture.
  • the bottom PDMS part is made on a silicon wafer without the photoresist patterns, but an arcuate surface is formed for to make a curved edge symmetrical to the top PDMS part of the device, such as by using a transparency film.
  • the cured top and bottom PDMS parts are surface-oxidized at same time in a plasma cleaner, which may be used at a "medium" power setting for 1 minutes at 2 torr air pressure.
  • a plasma cleaner which may be used at a "medium" power setting for 1 minutes at 2 torr air pressure.
  • the top PDMS part is aligned to the bottom PDMS part using a thin layer of methanol between the parts, and then bonded by heating, such at 70°C for 4 hours to evaporate the methanol. While oxidation of the parts will bond them, the methanol allows the parts to be aligned by providing a lubricant and preventing bonding until the methanol is evaporated.
  • the membrane edges for the emitter tips in the bonded PDMS device are trimmed to shape using iris scissors and a scalpel blade under a stereomicroscope along the photoresist pattern in the cast PDMS device as a guide for the emitter shape.
  • the angle of emitter tip and channel shape and size are shown in Figure 2C.
  • the devices are preferred to have small channels, for example, 100 ⁇ m wide and 30 ⁇ m deep, in order to minimize clogging problems when the device is fabricated and trimmed, or when a solution is injected.
  • the method may be used to produce emitters with channel dimensions larger or smaller, with the smaller dimensions limited only by the resolution capability of the soft lithography technique.
  • Figures 2A and 2B show one method of forming the curved shape and thin membrane along the edge of the PDMS device using a piece of curved transparency film. It is was critical to locate the position of the transparency film edge on the end of channel openings on the master wafer for the top PDMS part in order to control the thickness of the PDMS membrane edge.
  • the brass bar provides sufficient pressure to the film to control the membrane thickness at the channel openings of the emitters to less than 100 ⁇ m.
  • a block of material such as a resin block having an arcuate surface, may be used to form the curved, thin membrane, by positioning the block over the developed photoresist material at the end of the channel.
  • the pointed emitter tips 18, which are preferred to be 2-4 mm long, at each channel opening are made by trimming the membrane edge of the bonded PDMS device following the profile ( Figure 1) that is formed in the PDMS, using the photoresist pattern as a guide. After trimming, the shaped PDMS device is heated, such as at 70° C, to remove the prepolymer residue in the trimmed PDMS device. A total time for curing and heating may be 72 hours, to minimize the background signals from PDMS device.
  • Figure 3 may be drawn using a CAD program and printed on transparency film with a high-resolution printer, such as an image setter having 3556 dpi resolution.
  • the photomask designs define an angle for the sharply pointed emitter tips 26. This angle ⁇ may be 60 degrees, with a width of 100 ⁇ m, and length of 4 cm for the channels
  • the first photoresist pattern may be produced by coating negative photoresist 28 on a substrate 27, such as a silicon wafer substrate.
  • a required quantity of photoresist solution is coated on the silicon wafer substrate.
  • the wafer substrate may be chucked in a spin coater and spun, such as at 5000 rpm, following acceleration at 1000 rpm seconds "1 , for a total spin time of 25 seconds.
  • the coated wafer is baked, such as by prebaking at 55°C for 3 minutes, and then at 95°C for 25 minutes.
  • the photomask image for the first layer photoresist pattern ( Figure 3A) is exposed to radiation while positioned on the coated wafer.
  • the transparency with the pattern of first layer may be attached under a glass plate in the mask holder of the mask aligner.
  • a quantity of photoresist solution is coated on the first layer photoresist, such as by spin coating at 2500 rpm, following acceleration at 1000 rpm seconds "1 , for a total spin time of 20 seconds, and producing a second layer having a thickness of 150 ⁇ m.
  • the spin-coated wafer with two layer photoresist is baked, such as at 55°C for 3 minutes, and then at 95°C for 25 minutes.
  • the transparency with the pattern of the second layer ( Figure 3B) is aligned onto the exposed first layer photoresist using the mask aligner, and exposed to radiation.
  • the silicon wafer with the exposed first 28, 29 and exposed second photoresist is hard-baked, such as at 95°C for 15 minutes, and developed in 2-(1-methoxy)propyl acetate.
  • the heights of the photoresist pattern in each layer on the master wafer ( Figure 4A) are measured to verify thickness 30, 32, such as by using a profilometer.
  • Three or more layers may be produced by using the same method as set forth above wherein the second layer is added to the first layer. Additional layers may be added, as long as the underlying layers are not developed and postbaked prior to adding the additional layers.
  • the first step of the process for making PDMS device with emitter tips in order to connect fused- silica capillaries segments of FSCs are attached at the end points of the photoresist pattern for the channels ( Figure 3B) on the master wafer using the PDMS premixture as "glue.
  • the second step ( Figure 4B) for molding the PDMS replica on the master wafer the master wafer with two-layer photoresist pattern is surrounded to form a barrier or dam about the perimeter.
  • the ends of the reference points in the two layer photoresist pattern on the master wafer may be covered with a form 34 having an arcuate surface, such as a curved-profile resin bar, for producing the emitter tips of the, top part.
  • the barriers and resin bar are held in place, such as by clamping.
  • the degassed premixture for the top PDMS part is cast against the whole system on the master wafer which is had been silanized with (tridecafluoro-1 ,1 ,2,2-tetrahydrooctyl)-1 - trichlorosilane under vacuum.
  • the premixture on the master wafer is cured by heating, for example, at 70°C for 3 hours in an oven.
  • the cured top PDMS part is peeled from the master wafer.
  • the FCSs in the top PDMS part are removed and replaced with new longer cm segments of same dimension FSCs to make fluid connections to the channels.
  • the new FSCs are attached while flowing nitrogen through the capillary to prevent clogging, and the FSCs are secured in the place with PDMS premixture.
  • the bottom PDMS part which is symmetrical to top PDMS part of the device, is cast on a silicon wafer with the photoresist pattern identical to that of the top part without the channels.
  • the cured top and bottom PDMS parts are surface-oxidized at same time in a plasma cleaner as described above. After oxidation in air plasma, the top PDMS part is aligned to the bottom PDMS part using a thin layer of methanol between the parts under a stereomicroscope, and bonded by heating to evaporate the methanol.
  • the shape and size of emitter tip and channel for the PDMS ESI-emitter device are shown in Figure 2.
  • the photoresist pattern for the ESI-emitter is made on a substrate by a photomask design 40 ( Figure 5).
  • the photomask may be designed with a CAD program and printed on transparency film with a high-resolution image printer or setter, as described above.
  • the design of the PDMS device defines a sharply pointed emitter tip 42, which may be at an angle of 50°-70°.
  • the channels 44 may have, for example, a width of 100 ⁇ m, a depth of 30 ⁇ m, and a length of 4 cm.
  • Negative photoresist 45 s coated on a silicon wafer substrate 46 as described above.
  • the coated wafer substrate is baked as described above. After baking, the photomask image is patterned on the negative photoresist and exposed to radiation as described above.
  • the resulting wafer substrate is postbaked and developed as described above. After developing, the height of photoresist pattern on the master wafer is verified.
  • a desired quantity of polymer resin 50 is dropped on each emitter tip position in the photo resist pattern ( Figure 5A), and the resin is caused to flow to the end of the emitter tip photoresist pattern ( Figure 6A).
  • the resin is cured at room temperature overnight.
  • the viscous resin wets the photoresist pattern, forming a smoothly curved surface to the point of the emitter tip after curing.
  • a desired quantity of resin is placed immediately adjacent to the cured resin at each tip position of the photoresist pattern, and then cured at room temperature (Figure 6B).
  • a curved-profile block 52 which may be formed of PDMS and is fabricated to the same size as the photoresist pattern, is aligned onto the cured resin pattern ( Figure 6C), and additional resin 54, such as EPOFIX is filled between the block and the master wafer, and silanized with a releasing agent (tridecafluoro-1 ,1 ,2,2-tetrahydrooctyl)-1- trichlorosilane under vacuum. After curing overnight at an elevated temperature, the resin imprint is peeled from the block.
  • the resin premixture is, such as at a 16:1 ratio, with resin and hardener, and is degassed to remove bubbles under vacuum.
  • Capillaries which may be FCSs, are attached at the end points of the channels of photoresist pattern (Figure 5B) on the master wafer using the PDMS premixture as "glue" to provide openings for connecting longer FCSs to the cured PDMS device.
  • PDMS premixture as "glue”
  • the premixture on the master with resin imprint wafer is cured overnight in an oven, and the cured top PDMS part is peeled from the resin imprint, which is not adherent to PDMS.
  • the FCSs in the top PDMS part are removed and replaced with longer segments of same dimension FSCs to make fluid connections to the channels.
  • the new FSCs are attached while flowing nitrogen through the capillary to prevent clogging, and the FSCs are secured in the place with PDMS premixture.
  • the bottom PDMS part was made on a silicon wafer without the photoresist patterns using the resin imprint to make a curved edge symmetrical to the top PDMS part of the device.
  • the cured top and bottom PDMS parts are joined by first surface-oxidizing the parts at same time in a plasma cleaner as described above. After oxidation in air plasma, the top PDMS part is aligned to the bottom PDMS part using a thin layer of methanol between the parts under a stereomicroscope. The parts are bonded by heating to evaporate the methanol.
  • the angle of the emitter tip 58 and the channel 60 shape and size are shown in Figure 6E.
  • a MARINER ESI-TOF-MS instrument is used to acquire MS data.
  • the instrument was modified by adding a Z-axis adjustment made from an acrylic plate that attached edgewise to a microscope mechanical stage mechanism mounted to the existing XY adjustable ESI mount.
  • the channels of the microfabricated PDMS device are washed with methanol and water using a syringe pump.
  • the FCSs in the PDMS device were connected with a metal union to which ESI high voltage is applied.
  • a standard solution of 1 mg mL "1 each of angiotensin I and bradykinin in a 1 :1 (v/v) water- methanol solution, to which 0.1% acetic acid was added, is diluted to 10, 1, and 0.1 ⁇ M with same solvent.
  • the sample is injected into the PDMS device by the syringe pump with flow rate of 1-20 ⁇ l_ minutes "1 .
  • FSC 75 ⁇ m i.d. and 360 ⁇ m o.d.
  • the ESI performance of the FSC emitter is examined with sample concentrations of 10, 1 , and 0.1 ⁇ M and flow rates of
  • the distance of the emitter tip for the single channel and the four channel PDMS devices is varied from 5 to 10 mm in front of the orifice of the ESI-TOF- MS using an XYZ translational stage.
  • the ESI potential from the ESI power supply of the instrument is applied to the metal union connecting the FSC to the syringe pump.
  • the flow rate of nitrogen curtain gas varied from 500 to 2000 mL minutes "1 , and the interface is heated to 120° C.
  • the images of the Taylor cone and solution drop on the emitter were acquired with a CCD video camera with a 20 cm extension tube and 4X microscope objective as lens and using a video capture interface and software.
  • an array of the microfabricated emitters may be produced along the edge of a rectangular device for analysis of multiple samples.
  • Figure 7 shows an array of four such emitters, but any number of emitters may be produced along an edge of a device.
  • the device In the case of a linear array of such emitters, the device is moved linearly to position successive emitters in front of the ion entrance of the mass spectrometer.
  • the microfabrication methods may also be used to produce a circular device, wherein the array of emitters is arranged around the periphery of the device. In the latter case, the device is rotated to position successive emitters in front of the ion entrance of the mass spectrometer.
  • Electrospray Mass Spectrometry Results The emitter tips are positioned from 5 to 10 mm in front of MS orifice by the XYZ translational stage as shown schematically in Figure 7.
  • Figure 8A shows that when a solution of angiotensin I and bradykinin (10 ⁇ M each) is injected at flow late of 3 ⁇ L minutes "1 without ESI high voltage, a solution drop accumulated on the emitter tip of the PDMS device without wetting due to the hydrophobic nature of the PDMS surface. It has been reported that when a solution of angiotensin I and bradykinin (10 ⁇ M each) is injected at flow late of 3 ⁇ L minutes "1 without ESI high voltage, a solution drop accumulated on the emitter tip of the PDMS device without wetting due to the hydrophobic nature of the PDMS surface. It has been reported that when a solution of angiotensin I and bradykinin (10 ⁇ M each) is injected at flow late of 3 ⁇ L
  • FIG. 8B shows the change in shape of the droplet and formation of a Taylor cone upon application of ESI potential. In order to observe the Taylor cone of the electrospray, we used a single channel device to facilitate positioning the CCD camera.
  • FIG. 8B shows the Taylor cone on a 30° angle emitter at 8 mm from the orifice using a flow rate of 3 ⁇ L minutes "1 at 2.7 kV.
  • the electrospray performance of the PDMS emitter is durable for more than 30 hours.
  • ESI voltages of ⁇ 4 kV are applied to generate the electrospray directly from the edge opening at 5 mm position in front of the orifice.
  • the electrospray from the hydrophobic PDMS emitter device with a thin point could be performed using lower ESI voltages.
  • sample solutions of 10, 1 and 0.1 ⁇ M are injected into the PDMS device at flow rates of 1-20 ⁇ L minutes "1 .
  • TIC 9 shows the electrospray stabilities and the signal intensities monitored at 10 mm distance from the orifice with ESI voltage of 2.7 kV.
  • TICs are shown for the concentrations of 10 and 1 ⁇ M as well as PDMS background in the mass range between 200 to 700 m/z with an acquisition time of 1 seconds/spectrum for 20 minutes using flow rate of 3 ⁇ L minutes "1 .
  • the signal stability of the TIC is evaluated by measuring the relative standard deviation (RSD) of the signal intensity.
  • the PDMS background ( Figure 9A) has a 12.5% RSD.
  • Figure 11 shows the spectrum for a 1 ⁇ M sample sprayed with flow rate of 1 ⁇ L minutes "1 at the distance of 10 mm from the orifice using an acquisition time of 0.1 seconds/spectrum.
  • the LOD is observed as 1 ⁇ M at the 10 mm position with the S/N ratio of 18 for the [M+3H] 3+ peak of angiotensin I [a].
  • the sample concentration and the parameters of ESI-TOF-MS are kept constant, as is the 10 mm distance from the MS orifice.
  • the LOD with the 25 ⁇ m i.d. FSC tip is 0.01 ⁇ M (S/N 25).
  • the electrospray from the PDMS emitter is unstable, and when the sample concentration is decreased to 0.1 ⁇ M, the signal was undetectable.
  • the embodiments set forth above disclose the use of negative photoresist.
  • a positive photomask and positive photoresist may be used in a similar manner to produce the emitter of the invention.
  • the photomask may be produced as a positive, rather than a negative, by the methods set forth above.
  • Positive photoresist materials may be used and processed to produce the mold, which is then used to form the emitter according to the methods herein.

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Abstract

La présente invention concerne des émetteurs microfabriqués destinés à la spectrographie de masse en mode électronébulisation (ESI-MS), qui sont produits par un processus de lithographie «douce». Un substrat est revêtu avec un matériau photorésine. On positionne un masque photographique sur ce matériau photorésine. Ce masque photographique permet ou empêche sélectivement l'exposition de ce matériau photorésine au rayonnement, tel que le rayonnement UV. La plaquette qui en résulte est développée de sorte que la partie de la photorésine qui n'a pas été exposée au rayonnement soit retirée, et cette plaquette forme un moule. On prépare un matériau adapté, tel que du polydiméthylsiloxane (PDMS) sous forme d'un matériau en deux parties, puis on le verse sur cette plaquette, qui agit comme un moule, de façon à former une couche de l'émetteur. On peut former la couche adjacente de la même manière, la couche supérieure et la couche de fond étant assemblées, par exemple par application de plasma d'oxygène. le substrat peut être revêtu avec une seconde couche de matériau photorésine, après exposition au rayonnement de la première couche, mais avant le développement de cette première couche de façon à obtenir une forme plus complexe.
PCT/US2002/000705 2001-01-11 2002-01-09 Processus de microfabrication pour emetteurs de spectrometrie de masse en mode electronebulisation (electrospray) WO2002055990A2 (fr)

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AU2002243506A AU2002243506A1 (en) 2001-01-11 2002-01-09 Microfabrication process for electrospray ionization mass spectrometry emitters

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US60/260,655 2001-01-11

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WO2002055990A3 WO2002055990A3 (fr) 2002-11-07
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US7105810B2 (en) 2001-12-21 2006-09-12 Cornell Research Foundation, Inc. Electrospray emitter for microfluidic channel
US7537807B2 (en) 2003-09-26 2009-05-26 Cornell University Scanned source oriented nanofiber formation
FR2862006B1 (fr) * 2003-11-12 2006-01-27 Univ Lille Sciences Tech Sources d'electronebulisation planaires sur le modele d'une plume de calligraphie et leur fabrication.
US8785881B2 (en) 2008-05-06 2014-07-22 Massachusetts Institute Of Technology Method and apparatus for a porous electrospray emitter
US10125052B2 (en) 2008-05-06 2018-11-13 Massachusetts Institute Of Technology Method of fabricating electrically conductive aerogels
US8207496B2 (en) * 2010-02-05 2012-06-26 Thermo Finnigan Llc Multi-needle multi-parallel nanospray ionization source for mass spectrometry
US10308377B2 (en) 2011-05-03 2019-06-04 Massachusetts Institute Of Technology Propellant tank and loading for electrospray thruster
US9358556B2 (en) 2013-05-28 2016-06-07 Massachusetts Institute Of Technology Electrically-driven fluid flow and related systems and methods, including electrospinning and electrospraying systems and methods
US10141855B2 (en) 2017-04-12 2018-11-27 Accion Systems, Inc. System and method for power conversion
EP3973182A4 (fr) 2019-05-21 2023-06-28 Accion Systems, Inc. Appareil d'émission par électronébulisation

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US6087006A (en) * 1994-08-31 2000-07-11 Hitachi, Ltd. Surface-protecting film and resin-sealed semiconductor device having said film
US6033202A (en) * 1998-03-27 2000-03-07 Lucent Technologies Inc. Mold for non - photolithographic fabrication of microstructures
US6245227B1 (en) * 1998-09-17 2001-06-12 Kionix, Inc. Integrated monolithic microfabricated electrospray and liquid chromatography system and method
US6319634B1 (en) * 1999-03-12 2001-11-20 Corning Incorporated Projection lithography photomasks and methods of making

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WO2002055990A8 (fr) 2003-02-27
WO2002055990A2 (fr) 2002-07-18
WO2002055990A3 (fr) 2002-11-07
AU2002243506A1 (en) 2002-07-24

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