Abstract:
An electrospray system comprises a liquid extraction surface sampling probe. The probe comprises a probe body having a liquid inlet and a liquid outlet, and having a liquid extraction tip. A solvent delivery conduit is provided for receiving solvent liquid from the liquid inlet and delivering the solvent liquid to the liquid extraction tip. An open liquid extraction channel extends across an exterior surface of the probe body from the liquid extraction tip to the liquid outlet. An electrospray emitter tip is in liquid communication with the liquid outlet of the liquid extraction surface sampling probe. A system for analyzing samples, a liquid junction surface sampling system, and a method of analyzing samples are also disclosed.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application is claims priority to U.S. Provisional Patent Application No. 61/818,024, filed May 1, 2013, titled “AFM FLUID DELIVERY/LIQUID EXTRACTION SURFACE SAMPLING/ELECTROSTATIC SPRAY CANTILEVER PROBE,” the entire contents of which are incorporated herein by reference. 
    
    
     STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH 
     This invention was made with government support under contract No. DE-AC05-00OR22725 awarded by the U.S. Department of Energy. The government has certain rights in this invention. 
    
    
     FIELD OF THE INVENTION 
     This invention relates generally to a surface sampling and more particularly to liquid extraction surface sampling probes. 
     BACKGROUND OF THE INVENTION 
     The direct liquid extraction-based surface sampling approaches, which are applicable to the analysis of soluble components at a surface, provide several advantages over other surface sampling approaches. These advantages include the ability to on-line process the extracted sample post sampling and prior to analysis. While some problems like the analysis of certain absorbent surfaces impede this approach, the most significant limitation is the achievable sampling spatial resolution. The achievable spatial resolution is connected to the geometric configuration of the sampling probe as this configuration, along with solvent, and surface properties define the area of the liquid junction formed between the probe and the surface. As currently understood, this liquid junction size determines the effective sampling spatial resolution of one embodiment of a surface sampling probe which utilizes coaxial capillaries. This design provides extremely good liquid junction control and perturbations in the positioning of the inner and outer capillaries during sampling allow for sample trapping, reaction, and injection. However, robustness considerations limit the ultimate spatial resolution of this geometry because if the inner diameter of the inner capillary is too small, then the capillary easily plugs the extract flow path. The best spatial resolution using a continuous flow, dual capillary, liquid-extraction based probe claimed 12 μm resolution using solvent delivery and spray capillaries of at least 70 μm in outer diameter. To achieve a spatial resolution better than 1 μm will most likely require that the size of the inner diameter of the spray capillary be made smaller. However, a capillary smaller than 50 μm will likely result in plugging problem which will ultimately limit the resolution that can be achieved. 
     SUMMARY OF THE INVENTION 
     An electrospray system comprises a liquid extraction surface sampling probe. The probe comprises a probe body having a liquid inlet and a liquid outlet, and having a liquid extraction tip. A solvent delivery conduit is provided for receiving solvent liquid from the liquid inlet and delivering the solvent liquid to the liquid extraction tip. An open liquid extraction channel extends across an exterior surface of the probe body from the liquid extraction tip to the liquid outlet. An electrospray emitter tip is in liquid communication with the liquid outlet of the liquid extraction surface sampling probe. 
     The liquid extraction channel can be an open slotted channel extending across an exterior surface of the probe body from the liquid extraction tip to the liquid outlet. The aspect ratio of the liquid extraction channel can be greater than one. 
     The solvent delivery conduit can be a slotted channel extending across an exterior surface of the probe body from the liquid inlet to the liquid extraction tip. The aspect ratio of the slotted channel can be greater than one. 
     The electrospray emitter tip can be affixed to the probe body. The electrospray emitter tip can be integral with the probe body. The electrospray emitter tip can be provided on an electrospray nib. The electrospray nib can have a liquid nib channel for receiving extraction liquid from the liquid extraction channel and the liquid outlet, and delivering the extraction liquid to the electrospray emitter tip. 
     The electrospray nib can comprise a protrusion from the probe body. The protrusion can be shaped to provide the electrospray emitter tip. The electrospray nib can have a nib channel extending from the liquid outlet to the electrospray emitter tip. The nib channel can be an open slot. The nib channel can have an aspect ratio greater than one. 
     The solvent delivery conduit can be enclosed and pass through the probe body. The solvent delivery conduit can be an annular, inverted conical chamber within the probe body. The inverted conical chamber communicates with the liquid extraction tip at an apex end of the cone, and with the liquid inlet at the base end of the cone. 
     The probe can be configured as part of an atomic force microscope cantilever. 
     The surface of the liquid extraction channel can have a contact angle that is less than the contact angle of probe body surfaces adjacent to the liquid extraction channel. The contact angle can be less than 90°. 
     A system for analyzing samples can include a liquid extraction surface sampling probe. The liquid extraction probe can comprise a probe body having a liquid inlet and a liquid outlet, and having a liquid extraction tip, a solvent delivery conduit for receiving solvent liquid from the liquid inlet and delivering the solvent liquid to the liquid extraction tip, and an open liquid extraction channel extending across an exterior surface of the probe body from the liquid extraction tip to the liquid outlet. An electrospray emitter tip is in liquid communication with the liquid outlet of the liquid extraction surface sampling probe. An analysis device is provided for receiving the electrospray and analyzing the sample. The analysis device can be a mass spectrometer, an ion mobility spectrometer, and a differential mobility analyzer, among others. 
     The probe can be configured as part of an atomic force microscope cantilever. The cantilever is connected to an atomic force microscope such that the probe can also be used as an atomic force microscope tip. 
     A liquid junction surface sampling system can include a liquid extraction surface sampling probe. The liquid extraction surface sampling probe has a probe body having a liquid inlet and a liquid outlet, and a liquid extraction tip, a solvent delivery conduit for receiving solvent liquid from the liquid inlet and delivering the solvent liquid to the liquid extraction tip, and an open liquid extraction channel extending across an exterior surface of the probe body from the liquid extraction tip to the liquid outlet. The probe is configured as part of an atomic force microscope cantilever, and the cantilever is connected to an atomic force microscope. 
     The probe can further comprise an electrospray emitter tip in liquid communication with the liquid outlet of the liquid extraction surface sampling probe. The system can further comprise an analysis device for receiving the electrospray and analyzing the sample. The analysis device can be a mass spectrometer. 
     A method of analyzing samples includes the step of providing a liquid extraction surface sampling probe, comprising a probe body having a liquid inlet and a liquid outlet, and having a liquid extraction tip, a solvent delivery conduit for receiving solvent liquid from the liquid inlet and delivering the solvent liquid to the liquid extraction tip, and an open liquid extraction channel extending across an exterior surface of the probe body from the liquid extraction tip to the liquid outlet; and an electrospray emitter tip in liquid communication with the liquid outlet of the liquid extraction surface sampling probe. Solvent liquid is applied to a sample surface through the solvent delivery conduit and the liquid extraction tip of the liquid extraction surface sampling probe. Sample-containing solvent is removed through the liquid extraction channel. The sample-containing solvent is directed through the electrospray tip, the electrospray tip forming an electrospray from the sample-containing solvent. The electrospray is directed to an analysis device. The method can further comprise the step of using the liquid extraction surface sampling probe as an atomic force microscope tip, and taking atomic force microscope readings with the tip. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       There are shown in the drawings embodiments that are presently preferred it being understood that the invention is not limited to the arrangements and instrumentalities shown, wherein: 
         FIG. 1  is a schematic diagram of a liquid extraction surface sampling probe as configured with an atomic force microscope. 
         FIG. 2A  is a bottom view of a first embodiment of a surface sampling probe having a slotted liquid extraction channel. 
         FIG. 2B  is a cross-section. 
         FIG. 3A  is a bottom view of an alternative embodiment having a slotted solvent delivery conduit. 
         FIG. 3B  is a cross-section. 
         FIG. 4A  is a bottom view of an embodiment having an integral electrospray emitter tip. 
         FIG. 4B  is a cross-section. 
         FIG. 5A  is a bottom view of an embodiment having a conical solvent delivery conduit. 
         FIG. 5B  is a cross-section. 
         FIG. 6A  is a bottom view of an embodiment having a conical solvent delivery conduit and an integral electrospray emitter tip. 
         FIG. 6B  is a cross-section. 
         FIG. 7  is a magnified view of an electrospray nib having an electrospray emitter tip. 
         FIG. 8  is a cross-section of a liquid extraction channel. 
         FIG. 9  is a perspective view, partially in phantom, of a liquid extraction surface sampling probe having a slotted liquid extraction channel. 
         FIG. 10  is a perspective view, partially in phantom, of a liquid extraction surface sampling probe having an alternative liquid extraction channel. 
         FIG. 11A  is a perspective view, partially in phantom, of a liquid extraction surface sampling probe having a surface-applied liquid extraction channel. 
         FIG. 11B  is a cross section illustrating the surface application. 
         FIG. 12A  is a perspective view, partially in phantom, of a liquid extraction surface sampling probe having a surface-modified liquid extraction channel. 
         FIG. 12B  is a cross-section illustrating the surface modifications. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     There is shown in  FIG. 1  an analysis system  10  according to the invention. The analysis system  10  includes a liquid extraction surface sampling probe  14 . In one embodiment, the liquid extraction surface sampling probe  14  is mounted to a cantilever  18  of an atomic force microscope  22 . The liquid extraction surface sampling probe  14  receives solvent from a source  30  and directs the solvent to a sample surface  34 . The probe  14  can further comprise an electrospray emitter tip  38  which forms an electrospray  40  and directs the electrospray to a suitable analysis device such as inlet  42  of a counter-electrode  44  which can be the inlet to an analysis device such as a mass spectrometer or ion mobility spectrometer. 
     There is shown in  FIG. 2  a liquid extraction surface sampling probe  50 . The probe  50  has a probe body  54 , a liquid inlet  58 , and a liquid outlet  62 . A solvent delivery conduit  66  receives solvent liquid from the liquid inlet  58  and delivers the solvent liquid to a liquid extraction tip  70 . An open liquid extraction channel  74  extends across an exterior surface of the probe body  54  from the liquid extraction tip  70  to the liquid outlet  62 . In one embodiment, solvent leaving the liquid extraction tip  70  forms a liquid microjunction  78  with the sample surface  34 . Sample-containing solvent is extracted from the liquid extraction tip  70  into the liquid extraction channel  74  by capillary action and is wicked to the liquid outlet  62 . The probe body  54  can be mounted to a suitable structure such as arm  98 , which in one embodiment can be the cantilever of an atomic force microscope. 
     An electrospray emitter tip  86  can be provided. The electrospray emitter tip  86  can be of any suitable design. The electrospray emitter tip receives the sample-containing solvent from the liquid outlet  62  and forms an electrospray  90  that is suitable for analysis. The electrospray emitter tip  86  can be provided on a nib  94  that is secured to the probe body  54  by any suitable means. 
     There is shown in  FIG. 3  a liquid extraction surface sampling probe  100 . The probe  100  has a probe body  104 , a liquid inlet  108 , and a liquid outlet  112 . A solvent delivery conduit  116  is provided in the form of a open slotted channel extending across the surface of probe body  104 . The slotted solvent delivery conduit  116  delivers the solvent liquid to a liquid extraction tip  120 . An open liquid extraction channel  124  extends across an exterior surface of the probe body  104  from the liquid extraction tip  120  to the liquid outlet  112 . In one embodiment, solvent leaving the liquid extraction tip  120  forms a liquid microjunction  128  with the sample surface  34 . Sample-containing solvent is extracted from the liquid extraction tip  120  into the extraction channel  124  by capillary action and is wicked to the liquid outlet  112 . The probe body  104  can be mounted to suitable structure such as arm  132  which in one embodiment can be the cantilever of an atomic force microscope. 
     An electrospray emitter tip  136  can be provided on a nib  140  that is secured to the probe body  104  by any suitable means. The electrospray emitter tip  136  receives the sample-containing solvent from the liquid outlet  112  and forms an electrospray  144  that is suitable for analysis. 
     There is shown in  FIG. 4  a liquid extraction surface sampling probe  150 . The probe  150  has a probe body  154 , a liquid inlet  158 , and a liquid outlet  162 . A solvent delivery conduit  166  is provided in the form of an open slotted channel extending across the surface of probe body  154 . The slotted solvent delivery conduit  166  delivers the solvent liquid to a liquid extraction tip  170 . An open liquid extraction channel  174  extends across an exterior surface of the probe body  154  from the liquid extraction tip  170  to the liquid outlet  162 . In one embodiment, solvent leaving the tip  170  forms a liquid microjunction  178  with the sample surface  34 . Sample-containing solvent is extracted from the liquid extraction tip  170  into the extraction channel  174  by capillary action and is wicked to the liquid outlet  162 . The probe body  154  can be mounted to suitable structure such as arm  184  which in one embodiment can be the cantilever of an atomic force microscope. 
     An electrospray emitter tip  186  can be provided on a protrusion  190 . The electrospray emitter tip  186  receives the sample-containing solvent from the liquid outlet  162  and forms an electrospray  194  that is suitable for analysis. 
     There is shown in  FIG. 5  a liquid extraction surface sampling probe  200 . The probe  200  has a probe body  204 , a liquid inlet  208 , and a liquid outlet to  212 . A solvent delivery conduit  216  receives solvent liquid from the liquid inlet  208  and delivers the solvent liquid to a liquid extraction tip  220 . The solvent delivery conduit  216  is in the form of a conical annulus, such that solvent will be funneled down to the tip  220 . An open liquid extraction channel  224  extends across an exterior surface of the probe body  204  from the liquid extraction tip  220  to the liquid outlet  212 . In one embodiment, solvent leaving the liquid extraction tip  220  forms a liquid microjunction  228  with the sample surface  34 . Sample-containing solvent is extracted from the liquid extraction tip  220  into the extraction channel  224  by capillary action and is wicked to the liquid outlet  212 . The probe body  204  can be mounted to a suitable structure such as arm  232  which in one embodiment can be the cantilever of an atomic force microscope. 
     An electrospray emitter tip  236  can be provided on a nib  240  that is secured to the probe body  204  by any suitable means. The electrospray emitter tip  236  receives the sample-containing solvent from the liquid outlet  212  and forms an electrospray  244  that is suitable for analysis. 
     There is shown in  FIG. 6  a liquid extraction surface sampling probe  250 . The probe  250  has a probe body  254 , a liquid inlet  258 , and a liquid outlet to  262 . A solvent delivery conduit  266  receives solvent liquid from the liquid inlet  258  and delivers the solvent liquid to a liquid extraction tip  270 . The solvent delivery conduit  266  is in the form of a conical annulus, such that solvent will be funneled down to the tip  270 . An open liquid extraction channel  274  extends across an exterior surface of the probe body  254  from the liquid extraction tip  220  to the liquid outlet  212 . In one embodiment, solvent leaving the liquid extraction tip  220  forms a liquid microjunction  278  with the sample surface  34 . Sample-containing solvent is extracted from the tip  220  into the extraction channel  274  by capillary action and is wicked to the liquid outlet  262 . The probe body  254  can be mounted to a suitable structure such as arm  282  which in one embodiment can be the cantilever of an atomic force microscope. 
     An electrospray emitter tip  286  can be provided on a protrusion  290  that can be formed with the probe body  254  by any suitable means such as molding, milling or 3D printing. The electrospray emitter tip  286  receives the sample-containing solvent from the liquid outlet  262  and forms an electrospray  294  that is suitable for analysis. 
     There is shown in  FIGS. 7-9  an electrospray emitter nib  300  having an electrospray emitter tip  304  that is formed at the distal end of a nib body  308 . An electrospray emitter channel  312  carries sample-containing solvent to the electrospray emitter tip  304  where it is released from the electrospray emitter tip  304  as an electrospray for suitable analysis in a suitable analysis device. An electrospray nib channel  316  carries the sample-containing solvent from a liquid extraction channel  320  of the probe to the electrospray emitter channel  312 . 
     A suitable electrical contact  324  can be provided to create a voltage gradient between the electrospray emitter tip  304  and a counter-electrode so as to create an electric field appropriate to initiate the electrospray process. The voltage can be applied near or at the electrospray emitter tip or elsewhere in the probe or in the solvent source or solvent delivery conduit or at the counter-electrode. It is only necessary that the solvent be at the required voltage at the time that it is released from the electrospray emitter tip  304 . To electrospray a water solution requires an electric field at the spray tip of about 1.8×10 8  V/m. Solvents like methanol with a lower surface tension require less voltage. 
     The liquid extraction channel is open to the surrounding atmosphere such that there is a reduced opportunity for clogging by sample particulates. Flow to the liquid extraction tip of the probe body can be gravitational or can be promoted by a suitable pump or pressurized source of solvent. Upon reaching the liquid extraction tip, the solvent is placed in contact with the sample surface and is at the surrounding atmospheric pressure. Flow into and through the liquid extraction channel can be by or assisted by capillary action. Capillary action is promoted where the dimensions of each succeeding flow channel are reduced from the prior channel. Thus the dimensions of the liquid extraction channel are less than the dimensions at the liquid extraction tip  346 . As can be seen in  FIG. 7 , the dimensions of the electrospray nib channel  316  are reduced from the dimensions of the liquid extraction channel  320 . The dimensions of the electrospray emitter channel  312  are reduced from the dimensions of the electrospray nib channel  316 . The dimensions of a channel can taper in the direction of flow as shown for the electrospray nib channel  316  to promote capillary flow or wicking of the sample-containing solvent to the electrospray emitter tip  304 . The liquid extraction channel can have a width that is less than or equal to the width of the solvent orifice of the liquid extraction tip. The channels in one aspect are between 10-1000 nm or between 100-500 nm in width. The solvent flow rate can be less than 1000 nanoliters/min or between 0.1-500 nanoliters/min. Other flow rates are possible. 
     Flow through the liquid extraction channel will also be facilitated be the formation of the electrospray at the electrospray emitter tip. The charged electrospray will be pulled away from the electrospray emitter tip, drawing the liquid toward the electrospray emitter tip. This action of the electric field at the electrospray emitter tip will act to draw more sample-containing solvent through the liquid extraction channel. 
     The dimensions of the channels to foster capillary flow can vary. In one aspect, the width of the succeeding channels is reduced relative to prior channels, such that the electrospray nib channel  316  has a reduced width relative to the liquid extraction channel  320 . As shown in  FIG. 8 , the liquid extraction channel  320  can be formed by side walls  334  and base wall  338  as formed in the surface of probe body  342 . The aspect ratio of the liquid extraction channel  320  is the ratio of the height h to the width w. The aspect ratio should be greater than 1 to facilitate capillary flow. Similarly, the aspect ratio of succeeding flow channels can be greater than the aspect ratio of prior channels to facilitate capillary flow from channel to channel. 
     The liquid extraction channel can be constructed in any suitable manner that is open to the atmosphere surrounding the probe body. There is shown in  FIG. 10  a liquid extraction surface sampling probe  350  having a probe body  354 . Solvent is received through a suitable solvent delivery conduit  358  and passes through an orifice  362  of liquid extraction tip  366  to contact the sample. Sample-containing solvent is drawn up the side of the probe body  354  by means of an open liquid extraction flow channel  370  in the form of a strip of hydrophilic material. The hydrophilic material forming the liquid extraction channel  370  can the any suitable hydrophilic material, such as a material providing a contact angle with the solvent of less than 90 degrees. The hydrophilic character of the channel  370  should be greater than that of surrounding areas  374  of the probe body  354 . The surrounding areas  374  in this embodiment should thus be more hydrophobic than the material making up the liquid extraction channel  370 . In this manner, the solvent will be wicked up the liquid extraction channel  370  to the electrospray emitter nib  378  and electrospray emitter tip  382 . An electrospray emitter channel  386  or other suitable flow path can receive the sample-containing solvent from the liquid extraction channel  370  and deliver the solvent to the electrospray emitter tip  382 . 
     The manner in which the liquid extraction channel can be rendered more hydrophilic than surrounding areas of the probe body can be varied. There is shown in  FIG. 11  an embodiment in which the liquid extraction channel  370  is formed by a strip  390  of material that is applied to the probe body  354  and is more hydrophilic than surrounding areas  374  of its the probe body  354 . The strip  390  can comprise a surface providing a contact angle with the solvent of 90 degrees or less. There is shown in  FIG. 12  an embodiment in which the liquid extraction channel  370  is formed by surface modifying the probe body  354  as with nano-structure or etching  394  such that the liquid extraction channel  370  is more hydrophilic than surrounding areas  374  of the probe body  354 . The surface modification can provide a contact angle with the solvent of 90 degrees or less. It is alternatively possible to treat surrounding areas to be more hydrophobic that the liquid extraction channel, such that the aqueous solvent will be drawn through the liquid extraction channel. 
     The invention provides AFM devices capable of both dispensing and aspirating as necessary for a subsequent analysis of the extracted sample. The use of very low micrometer or smaller diameter capillaries to deliver and, especially, to retrieve and transport the extract at nanoliter/min flow rates is possible. In a continuous sampling mode a liquid junction is created with the sample surface and the electrospray process is continuous. In a tapping mode the liquid junction with the surface is broken and the electrospray process is initiated. In an alternative tapping mode, the liquid junction is created and broken repeatedly as the probe tip is moved to and from the surface and the electrospray is continuous. Alternating the sampling/spray and tapping modes of operation may allow analysis of wettable or absorbant surfaces. The AFM hardware and software also can provide built-in probe to surface liquid junction control. Also, the AFM capability provides automatic co-registration of spatial information from the multiple measurements of the surface within the same system. The AFM probe of the invention when used in conjunction with appropriate AFM hardware and software can be used for measurements such as topography, conductivity and current imaging among others. These measurements may be performed simultaneously with operation of the liquid extraction system, or separately. 
     This invention can be embodied in other forms without departing from the spirit or essential attributes thereof. Accordingly reference should be made to the following claims to determine the scope of the invention.