DEVICE AND METHOD FOR THE PRODUCTION OF AERODYNAMICALLY STABILIZED, ELECTRIFIED MICROSCOPIC JETS FOR THE TRANSPORT OF SAMPLES

Abstract

The present disclosure relates to a device for the transport of biological or other samples and for analysis thereof by interaction with a pulsed and focused energy beam, comprising: a transport capillary configured to house transport liquid, configured with an outlet section; a nozzle disposed concentrically and externally to the transport capillary, wherein said nozzle comprises a discharge section; and wherein the space between the transport capillary and the nozzle is configured to house a stabilizing gas; at least a first electrode for connecting a voltage to the transport liquid, in turn connected to a second electrode arranged at the outlet of the transport liquid capillary and the nozzle wherein said electrodes are subjected to an electrical potential difference. The disclosure also relates to a method comprising the use of said device.

Claims

1. A device for the production of aerodynamically stabilized, electrified microscopic jets, suitable for the transport of biological or other samples for molecular analysis, wherein the device comprises: a transport liquid capillary configured to receive a transport liquid, the transport liquid capillary comprising an outlet section, with diameter D.sub.l; a nozzle disposed concentrically and externally to the transport liquid capillary, wherein said nozzle comprises a discharge section; and wherein there is a stabilizing space between the transport liquid capillary and the nozzle configured to house a stabilizing gas; wherein the outlet section of the transport liquid capillary is configured to protrude from the discharge section of the nozzle by a distance not exceeding five times the opening diameter D.sub.g of said discharge section; at least one first electrode configured to provide a voltage to the transport liquid; a second electrode arranged at the outlet section of the transport liquid capillary at a distance H, and connected to the first electrode; wherein the density of the stabilizing gas .sub.g, the speed of the stabilizing gas .sub.g, the viscosity of the gas .sub.g and the opening diameter D.sub.g of the discharge section satisfy that the Reynolds number ${\mathrm{Re}}_g=\frac{{}_g.Math.v_g.Math.D_g}{{}_g}$ is between 0.1 and 5000; and wherein, given the following physical properties of the transport liquid: surface tension and electrical permittivity of vacuum .sub.o, the device is configured to subject said electrodes to an electrical potential difference (V) between 1 and 4 times the voltage ${\left(\frac{.Math..Math.D_l}{{\mathrm{.Math.}}_o}\right)}^{1/2}\mathrm{Ln}\left(\frac{H}{D_l}\right);$ which produces an electric field on the transport liquid emerging from the outlet section sufficient to stretch it in the shape of a stable conical meniscus.

2. The device according to claim 1, wherein the second electrode opposite to the first electrode connected to the transport liquid comprises a flat electrode, an annular or circular electrode and/or a conical electrode.

3. The device according to claim 1, further comprising a sample housing capillary, concentric and internal to the transport liquid capillary, configured to house a sample carrier liquid carrying said samples.

4. A method for the production of aerodynamically stabilized, electrified microscopic jets, suitable for the transport of biological or other samples for molecular analysis; wherein the method comprises the use of a device according to claim 1, and carrying out at least the following steps: introducing the samples into the transport liquid, which is forced to flow continuously through the transport liquid capillary whose outlet section, with diameter D.sub.l, is concentrically surrounded by the nozzle; given the following physical properties of the transport liquid: surface tension with either its vapor or vacuum, electric conductivity , density and electrical permittivity of vacuum .sub.o, the reference velocity of said transport liquid expressed as ${\left(\frac{}{{\mathrm{.Math.}}_o}\right)}^{1/3}$ is equal to or greater than 5.0 meters per second; given the viscosity of the transport liquid, the reference length $\frac{{}^2}{}$ is equal to or greater than 0.1 micrometer; the first electrode is connected to the transport liquid, and the second electrode is placed in front of the outlet section of the transport liquid capillary at a distance H, and a potential difference V between both is applied between 1 and 4 times the voltage ${\left(\frac{.Math..Math.D_l}{{\mathrm{.Math.}}_o}\right)}^{1/2}\mathrm{Ln}\left(\frac{H}{D_l}\right);$ which produces an electric field on the transport liquid emerging from the outlet section; a flow of transport liquid is forced through the transport liquid capillary equal to or less than 100000 times the reference flow expressed as $\frac{{\mathrm{.Math.}}_o}{};$ a stream of stabilizing gas is discharged concentrically with the transport liquid through the nozzle; given the density of the stabilizing gas .sub.g, the speed of the stabilizing gas .sub.g, the viscosity of the gas .sub.g and the opening diameter D.sub.g of said discharge section, the Reynolds number ${\mathrm{Re}}_g=\frac{{}_g.Math.v_g.Math.D_g}{{}_g}$ is between 0.1 and 5000; under all of the foregoing conditions the transport liquid forms at the outlet section of the transport liquid capillary a stable conical capillary meniscus from the apex of which emerges a steady and stable microscopic capillary jet that is a vehicle of the samples previously introduced into the transport liquid.

5. The method according to claim 4, wherein the reference velocity of said ${\left(\frac{}{{\mathrm{.Math.}}_o}\right)}^{1/3}$ transport liquid expressed as is greater than 50 meters per second.

6. The method according to claim 4, wherein a potential difference V between 2 and 3 times the voltage ${\left(\frac{.Math..Math.D_l}{{\mathrm{.Math.}}_o}\right)}^{1/2}\mathrm{Ln}\left(\frac{H}{D_l}\right);$ is established between the electrodes producing an electric field on the transport liquid emerging from the outlet section.

7. The method according to claim 4, wherein a flow of transport liquid through the transport liquid capillary is less than 500 times the reference flow expresses as $\frac{{\mathrm{.Math.}}_o}{}.$

8. The method according to claim 4, wherein in said discharge section, the Reynolds number ${\mathrm{Re}}_g=\frac{{}_g.Math.v_g.Math.D_g}{{}_g}$ is less than 1000 and greater than 10.

9. The method according to claim 4, wherein, given the viscosity of the transport liquid, the length $\frac{{}^2}{}$ is equal to or greater than 1 micrometer.

10. The method according to claim 4, wherein the samples are introduced into the transport liquid by suspension, solution, or emulsion either directly or by introducing them previously into another liquid which is subsequently mixed or emulsified in the transport liquid.

11. The method according to claim 4, wherein the device further comprises a sample housing capillary, concentric and internal to the transport liquid capillary, configured to house a sample carrier liquid carrying said samples, and wherein the samples are continuously introduced into the transport liquid flowing through the capillary, by means of a sample housing capillary discharging the sample carrier liquid inside the capillary.

12. The method according to claim 11, wherein a defined and convergent stream of the sample carrier liquid is finally generated flowing coaxially through the interior of the microscopic capillary jet entrained by the transport liquid.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0045] FIG. 1: General diagram of the device of the disclosure, according to a preferred embodiment thereof, showing the main elements of said device.

[0046] FIG. 2: Perspective view of the device of the disclosure, according to a preferred embodiment thereof.

[0047] FIG. 3: Micrograph of a preferred embodiment of the device of the disclosure, showing the conical meniscus and the microscopic capillary jet generated in the use of said device.

[0048] FIG. 4: Schematic of the device of the disclosure, according to a preferred embodiment thereof based on the use of a conical electrode.

[0049] FIG. 5: Schematic of the device of the disclosure, according to a preferred embodiment thereof based on the use of an annular electrode.

[0050] FIG. 6: Alternative configuration of introduction of the samples, through a capillary through which a carrier liquid flows, and which discharges into the liquid forming a defined and focused current.

NUMERICAL REFERENCES USED IN THE DRAWINGS

[0051]

TABLE-US-00001 (1) Samples (2) Transport liquid or matrix (3) Transport liquid capillary (4) Capillary outlet section (5) Stabilizing gas funnel or nozzle (6) Discharge section of funnel or nozzle (7) First voltage connection electrode to transport liquid (8) Second electrode opposite to the transport liquid, with which a difference of electric potential (V) is established (9) Stabilizing gas (10) Stable conical capillary meniscus (11) Microscopic stable capillary jet (12) Sample housing capillary (13) Sample carrier liquid

DETAILED DESCRIPTION

[0052] Different examples of preferred embodiments of the present disclosure on are shown in FIGS. 1-6 herein. In said Figures, it is seen how the device of the disclosure for sample (1) transport and analysis device of the disclosure preferably comprises a transport liquid capillary (3) configured to receive transport liquid (2) (or liquid matrix), configured with an outlet section (4) for forming a stable conical capillary meniscus (10), from which emerges a microscopic capillary jet (11) which remains stable and stationary, and which is a vehicle of the samples (1) which have been Introduced into the transport liquid (2) previously. To achieve this effect, the device further comprises a nozzle (5) or funnel arranged concentrically and externally to the transport liquid capillary (3), wherein said nozzle (5) comprises a discharge section (6). The space between the transport liquid capillary (3) and the nozzle (5) is configured to house a stabilizing gas (9).

[0053] The device further comprises at least one first electrode (7) for connecting a voltage to the transport liquid (2), and a second opposite electrode (8) arranged at the outlet section (4) of the transport liquid capillary (3) and the nozzle (5), wherein said electrodes (7, 8) are subjected to an electrical potential difference (V).

[0054] In different preferred embodiments of the disclosure, the second electrode (8) opposite to the electrode (7) connected to the transport liquid (2) may be, for example, a flat electrode (FIG. 1), a conical electrode (FIG. 4), or a circular or annular electrode (FIG. 5). Other electrode forms are equally feasible within the scope of the disclosure.

[0055] In another preferred embodiment of the disclosure, the outlet section (4) of the transport liquid capillary (3) is conical (see FIGS. 1-6).

[0056] In yet another preferred embodiment of the disclosure, the discharge section (6) of the nozzle (5) is conical (see FIGS. 1-6).

[0057] The samples (1) to be transported are preferably housed or introduced by the transport liquid capillary (3) (FIGS. 1, 4 and 5). However, in other preferred embodiments of the disclosure (FIG. 6), the device may comprise a sample housing capillary (12), concentric and internal to the transport liquid capillary (3), configured to house a sample carrier liquid (13) carrying said samples (1).

[0058] Another object of the disclosure relates to a process for the transport of biological or other samples and for analysis by interaction with a pulsed and focused beam of energy (for example by means of X-rays). Said method preferably comprises carrying out the following steps:

[0059] The samples (1) are introduced into a conveying transport liquid (2) or matrix, which is forced to flow continuously through a transport liquid capillary (3) whose outlet section (4), with diameter D.sub.l, is concentrically surrounded by a funnel or nozzle (5).

[0060] The outlet section (4) of the transport liquid capillary (3) is configured to protrude a distance of no more than five times the opening diameter D.sub.g of the discharge section (6) from said nozzle (5).

[0061] Given the following physical properties of the transport liquid (2): surface tension with either its vapor or vacuum, electric conductivity , density and electrical permittivity of vacuum .sub.o, the reference velocity of said transport liquid (2) expressed as

[00012]${\left(\frac{}{{\mathrm{.Math.}}_o}\right)}^{1/3}$

is equal to or greater than 5.0 meters per second; preferably larger than 50 meters per second.

[0062] Given the liquid viscosity , the reference length

[00013]$\frac{{}^2}{}$

is equal to or greater than 0.1 micrometer;

[0063] A first electrode (7) is connected to the transport liquid (2), and another planar electrode (8) is placed in front of the outlet section (4) of the transport liquid capillary (3) at a distance H, and a potential difference V between both of them is established between 1 and 4 times the voltage

[00014]${\left(\frac{.Math..Math.D_l}{{\mathrm{.Math.}}_o}\right)}^{1/2}\mathrm{Ln}\left(\frac{H}{D_l}\right),$

preferably between 2 and 3 times the foregoing voltage;

[0064] a flow of transport liquid (2) is forced through the transport liquid capillary (3) equal to or less than 100000 times the reference flow expressed as

[00015]$\frac{{\mathrm{.Math.}}_o}{};$

preferably less than 15 to 500 times said reference flow rate.

[0065] A stream of stabilizing gas (9) is discharged concentrically with the transport liquid (2) through the nozzle (5);

[0066] given the density of the gas .sub.g, the speed of the gas .sub.g, the viscosity of the gas g and the opening diameter D.sub.g of said discharge section, the Reynolds number

[00016]${\mathrm{Re}}_g=\frac{{}_g.Math.v_g.Math.D_g}{{}_g}$

is between 0.1 and 5000; preferably less than 1000 and greater than 10.

[0067] Under all of the above conditions, the transport liquid (2) forms at the outlet section (4) of the transport liquid capillary (3) a stable conical capillary meniscus (10) from the apex of which emerges a microscopic capillary jet (11) which remains stable and stationary, and is a vehicle of the samples (1) which have been introduced into the transport liquid (2) previously.

[0068] Preferably, the samples (1) are introduced into the transport liquid (2) by suspension, solution, or emulsion either directly or by previously introducing them into another liquid which is subsequently mixed or emulsified in the transport liquid (2).

[0069] In another embodiment of the method of the disclosure, the samples (1) are introduced continuously into the transport liquid (2) flowing through the transport liquid capillary (3), by means of a sample housing capillary (12) discharging the sample carrying liquid (13) inside the transport liquid capillary (3).

[0070] In another embodiment of the method of the disclosure, a defined and convergent stream of the sample carrier liquid (13) is generated which finally flows coaxially through the interior of the microscopic capillary jet (11) drawn by the transport liquid (2).