EP1713111A1

EP1713111A1 - Determining voltage-current-characteristics of an electrospray source

Info

Publication number: EP1713111A1
Application number: EP05110248A
Authority: EP
Inventors: Walter Schrenk
Original assignee: Agilent Technologies Inc
Current assignee: Agilent Technologies Inc
Priority date: 2005-11-02
Filing date: 2005-11-02
Publication date: 2006-10-18

Abstract

A method for determining a voltage-current-characteristic of an electrospray unit is described. The electrospray unit comprises an electrospray tip and an entrance electrode of a measurement unit, with the electrospraytip being adapted for generating a spray ion flow. The method comprises applying a voltage between the electrospray tip and the entrance electrode so as to direct at least parts of the spray ion flow towards the entrance electrode, and varying the voltage applied between the electrospray tip and the entrance electrode. The method further comprises detecting, in dependence on the applied voltage, an ion current between the electrospray tip and the entrance electrode, and at least partially determining a voltage-current-characteristic of the electrospray tip.

Description

BACKGROUND ART

The present invention relates to electrospraying.
US patent No. 6,462,337 to Li et al. discloses a method of providing ions to a mass spectrometer having an interface member with an orifice through which ions are received for analysis. A fluid is provided at a capillary tip of an electrospray ionization source and a potential difference is applied between the tip and the interface member so as to direct an ion beam from the tip toward and through the orifice. A field enhancing potential is applied on an auxiliary electrode so as to increase the electric field gradient from the capillary tip at least part way toward the interface member. A focusing potential may be applied to the auxiliary electrode to generate an electric field which decreases beam divergence from at least part way toward the interface member. Both the field enhancing and focussing potential may alternately be applied to the auxiliary electrode.
International patent application EP 2004/051024 "Electrospray Ion Generation with Stimulation" relates to an electrospray ionization device comprising a capillary tube arranged in a chamber and adapted for injecting a sample solution into the chamber. The electrospray ionization device further comprises a high voltage source adapted for generating an electric field between the tip of the capillary and an area of the chamber, thereby generating a spray of ion flow of the injected sample solution. To stabilize the ion generation and create a well-defined mass and size distribution of the spray flow, a generator is provided, which is adapted for generating an alternating signal with a frequency of at least 10 kHz. The generator is coupled to the capillary tube or the tip for a stimulation of ion droplets generation out of the injected sample solution in response to the generated signals.

DISCLOSURE

It is an object of the invention to improve the operating conditions of an electrospray unit. The object is solved by the independent claim(s). Further embodiments are shown by the dependent claim(s).
According to embodiments of the present invention, a method for determining a voltage-current-characteristic of an electrospray unit is provided. The electrospray unit comprises an electrospray tip and an entrance electrode of a measurement unit. The electrospray tip is adapted for generating a spray ion flow. The method comprises applying a voltage between the electrospray tip and the entrance electrode so as to direct at least parts of the spray ion flow towards the entrance electrode, and varying the voltage applied between the electrospray tip and the entrance electrode. The method further comprises detecting, in dependence on the applied voltage, an ion current between the electrospray tip and the entrance electrode, and at least partially determining a voltage-current-characteristic of the electrospray tip.
The voltage applied between the electrospray tip and the entrance electrode ionizes and vaporizes a fluid sample supplied to the electrospray tip. The ionized droplets are accelerated towards the entrance electrode. This spray ion flow gives rise to an ion current between the electrospray tip and the entrance electrode. By varying the voltage applied between the electrospray tip and the entrance electrode and determining the ion current as a function of the applied voltage, a voltage-current-characteristic of the electrospray tip is obtained. This voltage-current-characteristic contains a lot of information about the electrospray tip's properties and may therefore be used as a starting point for deriving various different parameters of interest. For example, the voltage-current-characteristic may be used for determining an optimum operation voltage, for tracking wear, for diagnostic purposes, for triggering replacement of the electrospray tip, and for various other purposes.
According to a preferred embodiment, the entrance electrode comprises a sampling orifice that defines the respective measurement unit's entrance path. Those parts of the spray ion flow that pass through the sampling orifice are subjected to further analysis by the measurement unit.
In a preferred embodiment, the measurement unit is a mass spectrometer. Further preferably, the measurement unit is a time-of-flight (TOF) mass spectrometer. The mass spectrometer is adapted for analyzing the mass distribution of those parts of the spray ion flow that pass through the sampling orifice. After the masses of the ionized species in the spray ion flow have been determined, the sample's various compounds may be identified.
In a preferred embodiment, the spray ion flow comprises both solvent ions and analyte ions, which are both accelerated towards the entrance electrode. Thus, both the analyte ions and the solvent ions contribute to the total ion current between the electrospray tip and the entrance electrode. Because of the solvent ions' contribution to the ion current, a current of considerable magnitude is obtained.
In a preferred embodiment, the voltage-current-characteristic is used as a starting point for determining parameters that indicate an actual state of the electrospray unit. In a further preferred embodiment, the method might comprise deriving, from the voltage-current-characteristic, a parameter that specifies an action to be taken. Possible actions might e.g. comprise setting the applied voltage to a preferred value, repositioning the electrospray unit, etc.
According to a preferred embodiment, the voltage-current-characteristic is acquired by performing a voltage sweep of the applied voltage. For example, the voltage may be continuously increased during a predefined period of time, and in dependence on the applied voltage, the corresponding ion current may be determined.
According to a preferred embodiment, a sudden rise of the detected ion current is observed at a certain voltage, which will furtheron be referred to as the "ignition voltage". The ignition voltage, which denotes the onset of the spray ion flow, can be derived from the acquired voltage-current-characteristic.
According to a further preferred embodiment of the invention, a voltage sweep is performed in the downward direction, with the applied voltage being continuously decreased as a function of time, and ion current is determined as a function of the applied voltage. In a further preferred embodiment, a so-called "cut-off voltage" is determined, with the cut-off voltage corresponding to a sudden decline of the measured ion current. As soon as the applied voltage drops below the cut-off voltage, the spray ion flow ceases.
In a preferred embodiment, voltage sweeps are performed both in the upward and in the downward direction, and both the ignition voltage and the cut-off voltage are determined.
In a preferred embodiment, the acquired voltage-current-characteristics are used for determining a preferred operation voltage of the electrospray unit. By setting the voltage applied between the electrospray tip and the entrance electrode to this operation voltage, a stable and reliable spray ion flow is accomplished. Because of the spray ion flow's improved stability, the accuracy of measurement results determined by the measurement unit is improved as well.
According to a preferred embodiment, a range of preferred operation voltages is determined by analyzing the voltage-current-characteristic and determining a voltage range that is characterized by a linear dependence between ion current and applied voltage. It has been found that in this voltage range of linear operation, a homogeneous vaporization and ionization of sample fluid is accomplished.
In yet another preferred embodiment, the operation voltage is set to a value above the ignition voltage. By setting the operation voltage to a value that is greater than the ignition voltage, it is made sure that the spray ion flow generated at the electrospray tip is not disrupted.
In yet another embodiment, the voltage-current-characteristic is taken as a starting point for deriving the electrospray tip's actual condition. In particular, from the voltage-current-characteristic, a parameter indicating wear may be derived. Thus, low performance electrospray tips may be identified and replaced before any non-reliable measurement results are acquired. According to a preferred embodiment, aging of the electrospray tip is monitored by tracking the value of the ignition voltage. For example, due to corrosion, the electrospray tip's ignition voltage might be shifted to a higher value.
In a preferred embodiment, the electrospray tip's actual condition is determined by analyzing fluctuations of the ion current. For example, the electrospray unit's actual mode of operation might be an irregular mode of operation, like e.g. a burst mode or a spitting mode. Irregular spray patterns indicate that the electrospray tip does not operate properly.
In a preferred embodiment, the various frequency components of the voltage-current-characteristic are evaluated. For example, fluctuations occurring on different time scales may be analyzed. Preferably, techniques like e.g. Fourier analysis may be used for determining the electrospray unit's mode of operation.
In a preferred embodiment, the acquired voltage-current-characteristic is used for positioning the electrospray tip relative to the measurement unit's entrance path. The spray ion flow between the electrospray tip and the entrance electrode depends both on the applied voltage and the geometric arrangement of the electrospray tip relative to the measurement unit's entrance path. Hence, the voltage-current-characteristic can be used for evaluating whether the electrospray tip is correctly positioned relative to the measurement unit's entrance path. If the voltage-current-characteristic does not have a desired shape, repositioning of the electrospray tip relative to the sampling orifice will be initiated.
According to a preferred embodiment, the voltage-current-characteristic is repeatedly determined while the electrospray tip is being repositioned. When the acquired voltage-current-characteristic gets close to a predefined characteristic, the electrospray nozzle is correctly positioned relative to the entrance path.
In a preferred embodiment, in order to adjust the electrospray tip's position relative to the entrance path, the axial distance between the electrospray tip and the entrance path is varied. Preferably, the axial distance is varied until an optimum voltage-current-characteristic is obtained. In a further preferred embodiment, the angle between the electrospray tip and the measurement unit's entrance path is varied. This allows adjusting the spray ion flow's direction relative to the measurement unit's entrance path.
According to embodiments of the present invention, a control unit for an electrospray unit is adapted for varying a voltage applied between an electrospray tip and an entrance electrode of a measurement unit, and for detecting, in dependence on the applied voltage, an ion current between the electrospray tip and the entrance electrode. The control unit is further adapted for at least partially determining a voltage-current-characteristic of the electrospray unit.
Embodiments of the present invention further relate to an electrospray unit for providing a spray ion flow to an entrance path of a measurement unit. The electrospray unit comprises an electrospray tip adapted for generating a spray ion flow, an entrance electrode of the measurement unit, and a power supply adapted for applying a variable voltage between the electrospray tip and the entrance electrode so as to direct at least parts of the spray ion flow towards the entrance electrode. Furthermore, the electrospray unit comprises a control unit as described above.
According to a preferred embodiment, the electrospray tip, which is adapted for vaporizing and ionizing a fluid sample, is implemented as a needle. According to an alternatively preferred embodiment, the electrospray tip is implemented as an electrospray nozzle that is part of a microfluidic device. The microfluidic device might e.g. comprise channels adapted for supplying fluid sample to the electrospray nozzle. The microfluidic device might further comprise one or more electrodes adapted for electrically contacting the electrospray nozzle. In a further preferred embodiment, microstructuring techniques are used for manufacturing the microfluidic device and the electrospray nozzle.
According to yet another preferred embodiment, the electrospray unit comprises a positioning unit, whereby the electrospray tip may be attached to the positioning unit, and whereby the positioning unit is adapted for positioning the electrospray tip relative to the entrance path of the measurement unit. For example, the positioning unit might be adapted for varying the axial distance between the electrospray tip and the sampling orifice. Further preferably, the positioning unit might be adapted for varying an angle of the electrospray tip relative to the measurement unit's entrance path. Further preferably, the positioning device might comprise one or more linear drives adapted for adjusting the electrospray tip's position relative to the entrance path.
Embodiments of the invention can be partly or entirely embodied or supported by one or more suitable software programs, which can be stored on or otherwise provided by any kind of data carrier, and which might be executed in or by any suitable data processing unit. Software programs or routines are preferably applied for controlling the voltage applied to the electrospray unit, and for evaluating a corresponding ion current.

BRIEF DESCRIPTION OF DRAWINGS

Other objects and many of the attendant advantages of embodiments of the present invention will be readily appreciated and become better understood by reference to the following more detailed description of embodiments in connection with the accompanied drawing(s). Features that are substantially or functionally equal or similar will be referred to by the same reference sign(s).
Fig. 1 shows an electrospray unit together with a measurement unit's entrance path;
Fig. 2 shows how a voltage-current-characteristic of an electrospray unit is acquired;
Fig. 3 shows two voltage-current-characteristics of a single electrospray unit that have been acquired by performing voltage sweeps in the upwards and downwards direction, respectively;
Fig. 4 illustrates the behaviour of a low-quality electrospray tip;
Fig. 5 shows the variation of an electrospray unit's voltage-current-characteristic as a function of operation time; and
Fig. 6 shows how ion current depends on the axial distance between an electrospray tip and a measurement unit's entrance path.
Fig. 1 shows an electrospray unit 1 together with an entrance path of a mass spectrometer 2. In the embodiment shown in Fig. 1, a microfluidic device 3 with an electrospray nozzle 4 is used as an electrospray ionization source. At the electrospray nozzle 4, a fluid supplied via a channel 5 is vaporized, in order to generate a spray ion flow 6. By means of a spray electrode 7 connected to ground, the fluid supplied via the channel 5 is kept at ground potential.
An electrospray ionization source generates ions at atmospheric pressure while a mass spectrometer requires a pressure of generally under 10^-4 Pascal. Therefore, mass analysis requires introducing the ions into a vacuum chamber. This can be achieved by means of a transfer capillary 8 having a small sampling orifice 9 (typically 0.1 to 2 millimeter in diameter), the transfer capillary 8 being located between a low pressure chamber of the mass spectrometer 2 and the atmospheric pressure region. The transfer capillary 8 comprises a metal-coated tip 10, which can either be an outer coating or an inner coating, if the tip comprises a small inner metal coating layer. A ring-shaped electrode 11 is located around the sampling orifice 9. A gold wire 12 provides an electric connection between the metal-coated tip 10 and the ring-shaped electrode 11. A voltage source 13 applies a voltage V_ESI between the spray electrode 7 and the ring-shaped electrode 11, whereby the voltage source 13 is controlled by a control unit 14. The voltage V_ESI might be in the range between 1 kV and 2.5 kV. For focussing the electric field between the electrospray nozzle 4 and the ring-shaped electrode 11, the electrospray unit further comprises a counter-electrode 15, with a voltage V_CE of approximately -500 V being applied between the ring-shaped electrode 11 and the counter-electrode 15. Hence, the counter-electrode 15 is kept at a potential between 0.5 and 2 kV.
The electric field between the electrospray nozzle 4 and the ring-shaped electrode 11 is adapted for accelerating electrospray ionization droplets towards and through the sampling orifice 9. The total spray ion flow comprises a flow 16 of analyte ions as well as a flow 17 of solvent ions, with the intensity of the flow 17 of solvent ions being much larger than the intensity of the analyte ion flow. A part of the flow 16 of analyte ions passes through the sampling orifice 9. The remaining part of the flow 16 of analyte ions as well as the flow 17 of solvent ions hit the ring-shaped electrode 11 and contribute to a total ion current (TIC), which is measured by a current determination unit 18.
The microfluidic device 3 is fixed to a positioning unit 19 that allows positioning the electrospray nozzle 4 in at least one of the x-, y- and z-direction. The positioning unit 19, which might preferably comprise one or more linear drives driven by stepper motors, might further be adapted for adjusting an angle Θ between the electrospray nozzle 4 and the mass spectrometer's entrance path.
Fig. 2 shows how a voltage-current-characteristic of the electrospray unit 1 of Fig. 1 is determined. First, the control unit 14 controls the voltage source 13 in a way that the voltage V_ESI applied between the spray electrode 7 and the ring-shaped electrode 11 is continuously increased as a function of time. Curve 20 shows this continuous increase of the applied voltage V_ESI. On the left ordinate axis 21, the applied voltage V_ESI is indicated, and time t is sketched along the abscissa 22. Curve 23 relates to the total ion current (TIC) measured between the electrospray nozzle 4 and the ring-shaped electrode 11, which is also shown as a function of time. The right ordinate axis 24 depicts the measured ion current (in nA). At a characteristic ignition voltage V_IGN, a sudden rise 25 of the measured ion current is observed. The ignition voltage V_IGN corresponds to the onset of the electrospray ion flow. When the applied voltage V_ESI surpasses a voltage of about 2500 volts, the control unit 14 starts to continuously decrease the applied voltage V_ESI, as a function of time, as indicated by curve 26. Curve 27 shows the corresponding ion current determined by current determination unit 17. At a characteristic cut-off voltage V_CUT, a sudden drop 28 of the measured current is observed, and the spray ion flow is stopped. The cut-off voltage V_CUT lies below the ignition voltage V_IGN.
After a measurement of the type shown in Fig. 2 has been performed, voltage-current-characteristics of the electrospray ionization unit can be derived. Fig. 3 shows two voltage-current-characteristics 29, 30 that have been acquired for one single electrospray ionization unit. Voltage-current-characteristic 29 corresponds to a voltage sweep in the upwards direction, whereas voltage-current-characteristic 30 corresponds to the downwards direction. The electrospray ionization voltage V_ESI (in volts), which ranges from 1800 volt to 2600 volt, is depicted along the abscissa 31, and the corresponding total ion current (in nA) is indicated on the ordinate axis 32. Voltage-current-characteristic 29 has been obtained by recording the total ion current as a function of a continuously increasing electrospray ionization voltage V_ESI, and therefore, the curve starts at the ignition voltage V_IGN. Voltage-current-characteristic 30 has been recorded while continuously decreasing the applied voltage V_ESI, and for this reason, the voltage-current-characteristic 30 extends down to the cut-off voltage V_CUT. Due to the electrospray unit's hysteresis, the ignition voltage V_IGN lies above the cut-off voltage V_CUT. In the example of Fig. 3, V_IGN ≈ 2125 volt, and V_CUT ≈ 2040 volt.
The voltage-current-characteristics 29, 30 shown in Fig. 3 can be used for determining an optimum range of operation voltages for the electrospray ionization unit. Initially, the voltage-current-characteristics are acquired and analyzed, then, the electrospray ionization unit's operation voltage is set to a preferred value that ensures a stable spray ion flow, and then, a given sample may be subjected to spray ionisation and analysed by the mass spectrometer.
The voltage-current-characteristics 29, 30 comprise various different regions that are characterized by different types of behaviour. For example, in voltage range 33, the measured ion current substantially shows a linear dependency on the applied voltage V_ESI. In the example shown in Fig. 3, the voltage range 33 of linear operation starts at the ignition voltage V_IGN = 2125 volt and extends up to an upper bound V_UP ≈ 2340 volt, and the corresponding ion currents range from 45 nA to 90 nA. Within the voltage range 33, the slope of the voltage-current-characteristics 29, 30 is approximately equal to 15 nA/100 V. When the applied voltage V_ESI exceeds the upper bound V_UP of the voltage range 33, a different kind of behaviour is encountered. For example, due to the high voltage, multiple charged ionized droplets might be generated, corrosion of the electrospray nozzle might occur, etc. These undesired artifacts cause a non-linear dependency between the applied voltage V_ESI and the measured ion current in the voltage range above V_UP.
From the above, it is clear that a preferred operation voltage V_OP should lie within the voltage range 33 of linear operation. Furthermore, the operation voltage V_OP should lie above the ignition voltage V_IGN, in order to prevent disruption of the spray ion flow. In the example of Fig. 3, V_OP has been set to 2250 volt. The corresponding ion current is approximately equal to 65 nA. With these settings, a stable operation of the spray ionization source is accomplished, and as a consequence, the accuracy of the mass spectrometric measurements is improved.
By acquiring voltage-current-characteristics of the electrospray ionization unit, it is further possible to evaluate the electrospray tip's actual condition. Thus, wear and aging of the electrospray tip may be monitored, and as soon as any severe degradation is observed, replacement of the electrospray tip may be initiated.
Fig. 4 shows two voltage-current- characteristics 34, 35 of a low-quality electrospray nozzle. Voltage-current-characteristic 34, which starts at the ignition voltage V_IGN, has been acquired by recording ion current as a function of a continuously increasing voltage. Voltage-current-characteristic 35 has been recorded while continuously decreasing the applied voltage. Voltage-current-characteristic 35 extends down to a cut-off voltage V_CUT, which lies below the ignition voltage V_IGN. In region 36, the ion current does not fluctuate significantly. However, in region 37, fluctuations of the detected ion current are observed, which indicate a non-stable mode of operation of the electrospray source. For example, the current fluctuations in region 37 might indicate a burst mode or a spitting mode of the electrospray ionization source. The fluctuations might e.g. be detected by performing a frequency analysis of the acquired voltage-current-characteristics, whereby fluctuations typically occur on a time scale of about one second. Fourier analysis might be a suitable method for detecting current fluctuations. In the example of Fig. 4, it can be concluded that the respective electrospray nozzle is of minor quality and should better be replaced.
Analysis of the acquired voltage-current-characteristics can further be used for monitoring wear of an electrospray tip. For example, by tracking ignition voltage over operation time, it is possible to monitor aging of an electrospray tip. An user may be informed in due time that a replacement of the electrospray tip is necessary.
The three-dimensional diagram of Fig. 5 has been obtained by repeatedly acquiring a voltage-current-characteristic of an electrospray tip during the electrospray tip's operation time. 300 different voltage-current-characteristics have been recorded during a time period of 150 hours, which means that every 0.5 h, a voltage-current-characteristic has been acquired. The number of a respective voltage-current-characteristic is indicated along axis 38. Axis 39 shows the applied voltage V_ESI (in volts), and axis 40 indicates a measured current (in nA). Fig. 5 shows the time dependence of an electrospray tip's voltage-current-characteristic. Initially, during the first 2.5 h, a voltage-current-characteristic 41 is obtained, which is characterized by a rather low ignition voltage. Then, during consecutive runs, voltage-current-characteristics 42 are acquired. The reason for the completely different shape of the voltage-current-characteristic 41 is that initially, the electrospray tip is at least partly covered with non-covalently bound materials. After these materials have been vaporized, the shape of the voltage-current-characteristic changes considerably.
An acquired voltage-current-characteristic of an electrospray unit might further be used as a starting point for repositioning the electrospray tip relative to the mass spectrometer's entrance electrode. By means of the positioning unit 19 shown in Fig. 1, the electrospray tip can be repositioned until a desired voltage-current-characteristic is obtained. The positioning unit 19 might comprise facilities for positioning the electrospray tip in at least one of the x-, y-, z-direction. Optionally, the angle Θ between the electrospray tip and the axis of the mass spectrometer's entrance path might be varied as well.
Fig. 6A shows how an electrospray tip 43 is axially positioned relative to a sampling orifice 44 of a mass spectrometer. The spray ion flow generated by the electrospray tip 43 comprises an analyte ion flow 45 and a solvent ion flow 46. Fig. 6B shows the measured ion current as a function of the axial distance between the electrospray tip 43 and the sampling orifice 44. As long as the distance in z-direction is rather small, the solvent ion flow 46 contributes to the total ion current. Accordingly, the total ion current is initially quite large. When the distance in z-direction becomes larger, only the analyte ion flow contributes to the ion current, whereas the solvent ions do not contribute to the ion current any more. By evaluating the diagram of Fig. 6B, the optimum operation range can be determined. Generally, the operation range is chosen such that solvent ion flow does not contribute to the total ion current.

Claims

A method for determining a voltage-current-characteristic of an electrospray unit (1),
the electrospray unit (1) comprising an electrospray tip (4) and an entrance electrode of a measurement unit (2), the electrospray tip (4) being adapted for generating a spray ion flow (6),
the method comprising:
applying a voltage between the electrospray tip (4) and the entrance electrode so as to direct at least parts of the spray ion flow (6) towards the entrance electrode;

varying the voltage applied between the electrospray tip (4) and the entrance electrode;

detecting, in dependence on the applied voltage, an ion current between the electrospray tip (4) and the entrance electrode, and at least partially determining a voltage-current-characteristic of the electrospray tip (4).
The method of claim 1, comprising at least one of the features:
the entrance electrode of the measurement unit comprises a sampling orifice, and at least parts of the spray ion flow are directed towards and through the sampling orifice;

the measurement unit is a mass spectrometer, preferably a time-of-flight mass spectrometer;

the spray ion flow comprises both contributions of solvent ions and analyte ions.
The method of claim 1 or any one of the above claims, further comprising at least one of:
deriving, from the voltage-current-characteristic, a parameter indicating an action to be taken;

continuously increasing the voltage applied between the electrospray tip and the entrance electrode during a predefined period of time;

determining an ignition voltage where a rise of the detected ion current occurs;

continuously decreasing the voltage applied between the electrospray tip and the entrance electrode during a predefined period of time;

determining a cut-off voltage where a decline of the detected current occurs.
The method of claim 1 or any one of the above claims, further comprising at least one of:
deriving, from the voltage-current-characteristic, a parameter indicating wear of the electrospray tip;

determining wear of the electrospray tip by tracking ignition voltage as a function of the electrospray tip's operation time;

analysing frequency components of the voltage-current-characteristic;

deriving, from the frequency components of the voltage-current-characteristic, a mode of operation of the electrospray unit;

detecting an irregular spray pattern of the electrospray unit.
The method of claim 1 or any one of the above claims, further comprising at least one of:
deriving, from the voltage-current-characteristic, a preferred range of operation voltages;

analysing a slope of the voltage-current-characteristic, and determining a preferred range of operation voltages showing a linear dependency between the applied voltage and the ion current;

analysing a slope of the voltage-current-characteristic, and determining a preferred range of ion currents;

locating a preferred range of operation voltages above an ignition voltage;

adjusting the electrospray tip's position relative to the measurement unit's entrance path in dependence on the voltage-current-characteristic.
The method of claim 1 or any one of the above claims, further comprising at least one of:
repeatedly determining a voltage-current-characteristic of the electrospray tip, and repositioning the electrospray tip relative to the measurement unit's entrance path in accordance with the respective voltage-current-characteristic;

varying, in dependence on the voltage-current-characteristic, an angle of the electrospray tip relative to the axis defined by the measurement unit's entrance path;

varying an axial distance between the electrospray tip and the measurement unit's entrance path in dependence on the voltage-current-characteristic.
An electrospray unit (1) comprising a control unit (14), wherein:
the control unit (14) is adapted for varying a voltage applied between an electrospray tip (4) and an entrance electrode of a measurement unit (2);

for detecting, in dependence on the applied voltage, an ion current between the electrospray tip (4) and the entrance electrode, and

for at least partially determining a voltage-current-characteristic of the electrospray unit (1).
The electrospray unit of claim 7, comprising at least one of the features:
the control unit is adapted for deriving, from the voltage-current-characteristic, a parameter indicating wear of the electrospray tip;

the control unit is adapted for deriving, from the voltage-current-characteristic, a preferred range of operation voltages.
The electrospray unit of claim 7 or any one of the above claims, the electrospray unit (1) being adapted for providing a spray ion flow (6) to an entrance path of a measurement unit (2),
the electrospray unit (1) comprising
an electrospray tip (4) adapted for generating the spray ion flow (6),

an entrance electrode of the measurement unit (2),

a power supply (13) adapted for applying a variable voltage between the electrospray tip (4) and the entrance electrode so as to direct at least parts of the spray ion flow (6) towards the entrance electrode.
The electrospray unit of claim 9, comprising at least one of the features:
the entrance electrode of the measurement unit comprises a sampling orifice, and at least parts of the spray ion flow are directed towards and through the sampling orifice;

the electrospray tip is one of: a needle or an electrospray nozzle of a microfluidic device;

the spray ion flow comprises both contributions of solvent ions and analyte ions;

the measurement unit's entrance path comprises a transfer capillary, with the transfer capillary's inlet at least partly coinciding with the sampling orifice;

a counter electrode adapted for focussing an electric field between the electrospray tip and the entrance electrode;

the measurement unit is a mass spectrometer, preferably a time-of-flight mass spectrometer.
The electrospray unit of claim 9 or any one of the above claims, further comprising a positioning unit adapted for adjusting, in dependence on the voltage-current-characteristic, the electrospray tip's position relative to the measurement unit's entrance path.
The electrospray unit of claim 11, wherein the control unit is adapted for repeatedly determining a voltage-current-characteristic of the electrospray tip, and wherein the positioning unit is adapted for repositioning the electrospray tip relative to the measurement unit's entrance path in accordance with the respective voltage-current-characteristic.
A mass spectrometer comprising
an electrospray unit according to claim 9 or any one of the above claims,

a mass spectrometry unit with an entrance path.
A software program or product, preferably stored on a data carrier, for controlling or executing the method of claim 1 or any one of the above claims, when run on a data processing system such as a computer.