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. 2026 Jul 28;61(8):e70085. doi: 10.1002/jms.70085

The ELVIS Probe: Combining Laser Pointer Desorption, Venturi‐Assisted Plume Transport, and Electrospray Ionization in a Simple Handheld Tool for Remote Ambient Mass Spectrometry

Andrea Ferreira Machado 1, Marcos Fernando Franco 2, Jorge Jardim Zacca 3, Deleon Nascimento Correa 2, Marco‐Aurélio De Paoli 4, Clécio Fernando Klitzke 5,✉, Marcos N Eberlin 1,6,✉
PMCID: PMC13409206  PMID: 42517288

ABSTRACT

Here we introduce the Electrospray Laser Venturi Ionization Sampling (ELVIS) probe, a handheld ambient sampling device that combines desorption performed by a simple laser pointer with Venturi‐assisted plume transport for remote mass spectrometric analysis. The ELVIS probe is portable, inexpensive, easy to operate and to point to a target area and exhibits no detectable carryovers. The probe can also be readily coupled to most atmospheric‐pressure ionization sources, as demonstrated herein for electrospray ionization (ESI). The ELVIS probe employs Venturi pumping to provide efficient and controllable aspiration of the laser‐generated plume. This mechanism transports analyte vapors directly to the ion source, substantially reducing signal dispersion that commonly occurs during open‐air sampling or when carrier gases are used. Desorption is achieved using a compact, low‐cost, yet highly effective 0.5 W laser pointer, enabling the sampling of a wide range of analytes from diverse matrices. Notably, the ELVIS probe is particularly advantageous for sampling target analytes deeply embedded within complex matrices, where spray‐based or liquid‐extraction ambient MS techniques often fail. For proper ionization, the probe was coupled to a commercial ESI source and successfully applied to the detection of illicit drugs, plasticizers in PVC, caffeine directly from a coffee bean, and pesticide residues on the wings of a deceased honeybee. The advantageous coupling of the ELVIS probe with Venturi‐assisted easy ambient sonic‐spray ionization is also discussed.

Keywords: ambient mass spectrometry, forensic chemistry, honeybee poisoning, illegal drugs, laser desorption, MasSpec Pen, plasticizer analysis, remote mass spectrometry, Venturi pumping

1. Introduction

Ambient mass spectrometry [1, 2] has profoundly revolutionized MS analysis by introducing a series of new tools for simple [3], direct, sample preparation and chromatography‐free analysis. Sometimes remote sampling with handheld tools operating at open atmosphere for many analytes on their original matrices or when placed on auxiliary surfaces has also been developed. Spray‐based desorption/ionization techniques such as those based on electrospray ionization (DESI) [4] and sonic spray (EASI) [5, 6] or electronically excited gas‐based techniques such as direct analysis in real time (DART) [7] have formed a major class of techniques that presently form the extremely diverse field of ambient MS with a great range of applications. In the spray‐based techniques, the desorption process relies therefore on the ability of the charged droplets or heated gas to efficiently dissolve target analytes from the surfaces of different matrices.

Limited solubility or slower dissolution dynamics, such as those observed for proteins and other large molecules, as well as the inherent inability of the solvent droplets to penetrate the matrix, have restricted the use of spray‐based techniques and therefore limit the scope of ambient MS. These limitations become crucial, for instance, when the target analyte is deeply or firmly embedded within a solid matrix, such as during the screening of plasticizers in polymers or dyes in cellulose surfaces [8].

Undoubtedly so far, the most successful ambient MS technique has been the MasSpec Pen [9, 10]. This handheld, portable, non‐destructive, and remote liquid extraction probe places a droplet of a solvent on a surface, which rapidly extracts soluble analytes located on its top layer and transfers the liquid extract, via a flexible PTFE tube, directly to the inlet of a mass spectrometer. It is therefore the vacuum inside the mass spectrometer that aspirates the liquid extract through the tubing into the heated MS inlet, where the analytes are ionized and characterized by MS. Although still undetermined, ionization during MasSpec Pen analysis seems to follow a mechanism that resembles solvent‐assisted inlet ionization, rather than classical ESI, since no high voltage is applied. We argue that, most likely, since the vacuum‐induced, voltage‐free, self‐aspirating heated ionization process employed should cause vigorous liquid shearing and the formation of very tiny solvent droplets with unbalanced charge distribution, that the ionization mechanism of “inlet ionization” closely resembles that of sonic spray [11], or perhaps even more closely that of Venturi‐assisted easy sonic spray ionization (V‐EASI) [12].

MasSpec Pen applications have been numerous and highly successful, but this rapid liquid extraction probe is intrinsically limited to analyte molecules soluble in a specific solvent and to those lying or being placed on the very top of surfaces or solid matrices. To overcome these limitations, laser desorption/ablation (LD[A]) seems ideal since this technique promotes more energetic thermal analyte desorption and can penetrate deeper within the matrix or reach highly constrained points on the analyte surface.

Using commercial high‐power and intricate laser sources, a series of ionization techniques have been developed using efficient LD(A) but performed as close as possible to an ESI source to use ESI as the main ionization process. The resulting laser plume containing analyte vapor is therefore merged as efficiently as possible into the stream of ESI charged droplets. This series combining LD(A) plus ESI includes techniques known as electrospray‐assisted laser desorption ionization (ELDI) [13], matrix‐assisted laser‐desorption ESI (MALDESI) [14], laser ablation ESI (LAESI) [15], and infrared laser‐assisted desorption ESI (IR‐LADESI) [16]. When compared with the direct “droplet desorption” of the MasSpec Pen, LD(A) presents improved spatial resolution down to 1 μm and high desorption yields but often with the price of substantial thermal damage. For imaging mass spectrometry (IMS), LD‐based techniques have produced MS images with the highest spatial resolutions [17]. The ablation energy (power and wavelength) is adjustable, and many commercially available laser sources have been used.

In these laser‐plus‐ESI techniques, LD(A) is performed as close as possible to the ESI plume, but spatial constraints still cause the laser plume to travel certain distances in open air, where it experiences diffusion, thus sensitivity is reduced. The ion source design must also be considerably modified to allow LD(A) to be performed as close as possible to the ESI plume and at the best possible angle [18]. There are also other limitations related to sample size and 3D geometry.

To overcome these spatial constraints, techniques employing remote LD(A) have been developed such as one that uses a remote LAESI chamber incorporating an optical microscope and a pulsed nanosecond mid‐IR laser [19]. Ablated particulates are transported to the ESI source through a 60‐cm‐long transfer tube using N2 as the carrier gas. But the remote LAESI system remained complex and heavy, hence not easily portable or handheld, and dilution of the analyte vapor in the N2 carrier gas was observed to reduce dynamic range and signal intensity, which dropped to only 27% of that of the original LAESI source.

For the transport of the desorbed vapors, the Venturi effect (Figure 1) has been an alternative to the use of carrier gas or the vacuum from the mass spectrometer. This effect causes substantial reduction in pressure when fluid flows through a constricted section of a channel or tube. As the cross‐sectional area decreases, the fluid velocity proportionally increases, and its static pressure correspondingly decreases according to Bernoulli's principle. This pressure drop has been used to induce suction, entrain surrounding gases or liquids, or enhance mixing and transport processes [20].

FIGURE 1.

FIGURE 1

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The Venturi effect.

We reasoned that the Venturi effect [21] could provide an optimal solution for further enhancing laser desorption (LD[A]) in remote laser‐based ambient mass spectrometry. We have recently employed the Venturi effect to develop two versions of self‐pumping, Venturi‐assisted V‐EASI sources [12, 22]. With the aid of Venturi suction, we further hypothesized that a modest yet sufficiently powerful laser pointer could generate adequate analyte desorption to produce substantial ion currents when coupled with an efficient ionization technique such as ESI. Herein therefore, we describe a handheld sampling device called the ELVIS (Electrospray Laser Venturi Ionization Sampling) probe, which employs a simple 0.5‐W laser pointer directly connected to an ESI source. The device enables remote and mobile, Venturi‐assisted, gentle laser desorption of molecules from a variety of matrices, while providing efficient analyte transfer and ionization with greatly reduced carryovers and minimal thermal damages.

2. Experimental

2.1. Materials

Erythroxylum coca leaves, Cannabis sativa leaves, flowers and branches, ecstasy tablets, and LSD blotter samples were provided by the Brazilian Federal Police. Samples of Arabic Coffee beans were purchased from a local market. The PVC tube was purchased from a local market. The deceased honeybee ( Apis mellifera ) was collected from an agricultural landscape in southern Brazil.

2.2. The ELVIS Probe

Figure 2 delineates major details of the ELVIS probe. The (C) Venturi device was assembled from easily available and inexpensive common commercial GC–MS gas‐line components, as described elsewhere [12]. The flow of high‐velocity nitrogen gas passing through C is used to pump the LD plume and direct it through a 0.8‐mm PTFE tube to the plume of ESI charged droplets formed from pure methanol. The (B) conical shape of the ELVIS tip was shaped to maximize vapor collection. To minimize costs and allow the construction of as simple an apparatus as possible, a (A) portable and inexpensive 22 × 110‐mm laser pointer of 0.5 W and wavelength of 532 nm (Green Laser Pointer Pen) was used. We did not use exactly the ELVIS design of Figure 2, but a draft version that very much mimics it and, in practice, produces similar results.

FIGURE 2.

FIGURE 2

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General schematic of the handheld ELVIS probe coupled to a commercial ESI source that illustrates its application for the screening of honeybee poisoning by simply pointing the laser pointer directly on the bee wings. (A) 0.5‐W laser pen, (B) removable ELVIS tip for cleanup, and (C) Venturi pump.

2.2.1. Safety Note

Although the 0.5‐W laser pointer used in this work is something between class IIIB or at the very lowest limit of a Class IV laser (lasers capable of causing eye damage), it should always be operated with great care, ideally by an experienced chemist or technician wearing appropriate certified protective eyewear made with proper laser absorbers. To block all possible laser reflections, we also recommend positioning the ELVIS probe as close as possible to the sample surface, with the black conical tip of the cartridge (Figure 2C) touching the analyte surface. The entire ELVIS probe setup may also be placed inside a black box with a protective glass window to block any reflected laser light while allowing a proper view of target areas. The laser pointer we used also included a safety key switch, allowing it to be locked after expert use to prevent unauthorized operation.

Note from the ELVIS schematic in Figure 2 that no modification whatsoever was needed for the commercial ESI ion source, since (C) the needle of the Venturi device could be easily and directly connected to it. For the FT‐ICR instrument used, we removed only a small glass window to allow introduction of the ELVIS needle. The best position and angle of the ELVIS needle were finely adjusted to achieve optimal sensitivity. In our system, an angle of ca. 45° was found to be optimal, and the needle tip was positioned approximately 2.0 cm from the instrument skimmer. For all data presented herein, a 20‐cm‐long flexible PTFE tube was used, but tubes as long as 1 m were tested with only ~40%–60% signal reduction (from 20 cm to 1 m).

The 0.5‐W laser pointer produced a laser spot approximately 2 mm in diameter at the target surface placed a few cm far from the pen. Laser irradiation typically ranged from 0.5 to 3 s and was adjusted to generate sufficiently intense ion current, generally corresponding to total ion currents (TICs) on the order of 106 counts. We did not measure the depth of laser penetration but found it to vary substantially as a function of irradiation time, the number of laser shots, and the physicochemical properties of the matrix. But as a qualitative indication of its ablation capability, note that prolonged (~2 min) or repeated laser irradiation was sufficient to perforate a standard sheet of printing paper. Typically, the fluence of a 0.5‐W laser pen for a surface placed a few cm away is around 20 J/cm2.

3. Results and Discussion

The possibility to perform remote LD(A) using a portable, mobile, and relatively small and simple 0.5‐W laser pointer brings therefore great flexibility to the ELVIS probe, allowing it to handle different types of samples with contrasting shapes and sizes, and rough surfaces such as round plastic tubes, connections, bottles, plant parts, coffee beans, or bee wings. Since it is essentially a compact manually‐operated pointer, it also allows inspection of as many areas and as many times as desirable, and as deep as necessary into the matrix (by laser ablation), from the sample surface.

Note also from Figure 2 that many parameters can be varied for best ELVIS probe performance, such as (a) the power of the laser beam (laser pointers from 0.5 W up to 10 W are available), (b) the duration and repetitions of the laser shots, (c) the depth of matrix penetration by applying prolonged or multiple laser shots, (d) the intensity of the vacuum suction that can be adjusted by controlling the N2 flux reaching the Venturi pump, (e) the spatial positioning of the ELVIS needle for best possible mixing of the laser and ESI plumes, and (f) the ESI variables such as solvent, additives (we used no additives both in the positive and negative ion modes) and voltages.

To test the general use and sensitivity of the ELVIS probe, we were faced with many possible cases from which we could arbitrarily select some proof‐of‐principle samples. Note particularly that we did not test the ELVIS probe for tissues, since we believe that the MasSpec Pen with its gentle “live‐friendly” water extraction plus thermal or laser damage‐free characteristic is probably unbeatable for such purpose.

Figure 3 shows the ELVIS(−)‐MS of a Cannabis tablet, which is one of the oldest and most commonly abused drugs in the world [23]. A laser shot of ca. 20s was used, producing a quite intense (2 × 106 counts) TIC of ~0.5 min wide, and abundant mass spectra in which molecules such as cannabidiol/cannabinol (CBD/CBN) of m/z 309.1862, tetrahydrocannabinol of m/z 313.2176 (Δ9‐THC), tetrahydrocannabivarinic acid of m/z 329.1761, and cannabigerolic acid of m/z 359.2233 were efficiently and unequivocally (exact masses with less than 1‐ppm deviation) detected as major and abundant ions.

FIGURE 3.

FIGURE 3

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(a) Typical TIC and (b) ELVIS(−)‐MS acquired directly from the surface of a seized marijuana tablet.

Figure 4 now shows the ELVIS(−)‐MS from three major plant parts of marijuana. Note much greater Δ9‐THC/(CBD + CBN) ratio for the marijuana leaf as compared to its flower and stem. In marijuana tablets, the Δ9‐THC/(CBD + CBN) ratio is used for aging and for forensic traceability, but extraction procedures followed by time‐consuming chromatography separation before MS analysis is often employed [24]. Similar ambient MS results of Cannabis leaves has also been obtained by desorption atmospheric pressure photoionization (DAPCI) [25] and direct analysis in real time (DART) [26].

FIGURE 4.

FIGURE 4

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ELVIS(−)‐MS acquired directly from the surface of Cannabis sativa plant parts. (a) leaves, (b) flower, and (c) steam.

We also applied the ELVIS probe to a dry leaf of Erythroxylum coca (Figure 5). Such leaves are known to contain cocaine (the most widely used natural psychotropic drug) from 0.5% to 0.8% in dry weight [27]. Cocaine from E. coca leaves is commonly analyzed via liquid extraction followed by LC‐MS [28] or GC–MS [29] The ELVIS(+)‐MS of a dry cocaine leaf (Figure 5) shows efficient desorption and ionization of the expected set of its three phytomarkers, that is: protonated methylecgonidine of m/z 182.1177, ecgonine methyl ester of m/z 200.1283 and cocaine of m/z 304.1545. This unequivocal and direct characterization of a drug from its source leaf should indeed be useful for forensic analysis. We performed DESI(+)‐MS and EASI(+)‐MS directly from the same dried cocaine leaf (spectra not shown), but spectra were of much lower quality, noisy and with nearly undetected ions.

FIGURE 5.

FIGURE 5

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ELVIS(+)‐MS obtained directly from a dried Erythroxylum coca leaf.

Ecstasy tablets have gained worldwide popularity among drug users, and their main active molecule 3,4‐methylenedioxy‐methamphetamine (MDMA) has been detected in such tablets using several ambient MS techniques such as EASI‐MS [30] and DART‐MS [31]. But the surface of the tablet should normally be scratched before analysis and sometimes, due to the variable physical–chemical characteristics of the tablet, poor responses are attained. We applied the ELVIS probe to ecstasy tablets and noted that indeed, after a few laser shots that promote deeper ablation, quite abundant spectra were recorded, regardless of the color of the tablet (green, blue, brown, white, pink, or yellow), as Figure 6 exemplifies for the pink area. ELVIS(+)‐MS shows abundant ions for protonated MDMA of m/z 194.1176 as well as its known fragment ions of m/z 163.0754, 135.0441, 133.0645, and 105.0699, likely formed due to in‐source CID [32].

FIGURE 6.

FIGURE 6

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ELVIS(+)‐MS obtained directly from the surface of an ecstasy tablet after several laser shots. The ions marked with asterisks are known fragments of protonated MDMA of m/z 194.1176.

Coffee is one of the most valuable commodities in the world, being the second most consumed beverage globally. For roasted coffee beans, ESI(+) and ESI(−)‐MS fingerprintings of their extracts have been used to distinguish between roasted Arabica and Robusta coffee beans [33] and to evaluate roasting levels [34]. Ambient MS techniques such as DART‐MS [35] and EASI [36] have also been applied to directly characterize coffee beans. ELVIS(+)‐MS, after a few shots that were used to “clean” the surface from interferences, provides quite unique, clean, and representative coffee bean fingerprintings (Figure 7) directly from the nearly undisturbed coffee bean. We have also applied the MasSpec Pen for beam coffee analysis [37].

FIGURE 7.

FIGURE 7

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ELVIS(+)‐MS obtained directly from the laser‐cleaned surface of an Arabica roasted coffee bean. The ion of m/z 413.2664 is likely the protonated molecule of a common phthalate contaminant, that is [DEHP + Na]+, see Figure 8, deeply positioned within the bean.

MS screening of additives in polymers usually employs tedious and time‐consuming solvent extractions and chromatographic separations [38], whereas ambient MS techniques based on droplet or liquid extraction often fail. The ELVIS probe seems therefore attractive to characterize additives in polymeric materials due to its penetration power. As a test case, we applied it to a polyvinylchloride (PVC) material [39]. Indeed, as Figure 8 shows, ELVIS(+)‐MS detected three phthalate ions, that is, those of m/z 429.2410 and 413.2662 corresponding to [DEHP + K]+ and [DEHP + Na]+ and that of m/z 301.1411 corresponding to [DBP + Na]+.

FIGURE 8.

FIGURE 8

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ELVIS(+)‐MS obtained directly from a PVC surface.

3.1. More Challenging Trace Analysis

LSD is another major drug of abuse and one of the most potent mind‐altering chemicals. A commonly illegally commercialized form of LSD is via “blotters,” that is, in small square pieces of paper similar to letter stamps which have been soaked in very diluted solutions of LSD [40]. The LSD concentration in such blotters is, therefore, at low trace levels, on the order of just 50–100 μg per stamp [41].

DAPPI‐MS, an ambient MS technique based on desorption by hot toluene or acetone vapors has been applied to detect LSD in these stamps, but the spectra were quite noisy, which could lead to false negatives [42]. LSD stamps analyzed directly by ELVIS(+)‐MS (Figure 9) also produced an overall low abundant pair of isotopologue ions for protonated LSD, those of m/z 324.2073 and m/z 325.21067, but with sufficiently high signal‐to‐noise ratios (higher than 50). No loss of signal was noted for the different colored regions (green, red, blue, yellow, or white) within the stamp surface, showing that the LD(A) efficiency for the ELVIS probe employing a green laser pointer is unaffected by substantial dye effects. Cocaine was also detected as an abundant ion (19%) for its protonated molecule of m/z 304.1546.

FIGURE 9.

FIGURE 9

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ELVIS(+)MS obtained directly from the surface of an LSD stamp. The insert shows the unambiguous and high signal‐to‐noise (> 50) detection of LSD by its pair of 12C/13C isotopologue ions of m/z 324.2073 and m/z 325.21067 for its protonated molecule.

Honeybees, which are essential in food production for their key action for pollinized crops [43], have experienced worrying population decline [44] that has been directly related to the use of pesticides in agriculture [45]. Given the complexity of the bee matrix, and the trace levels of contaminants, investigation of possible pesticide contamination on cases of sudden bee mortality requires the collection of pools of many bee samples (10 to 20 at least) followed by elaborated liquid–liquid or solid‐phase extractions (SPEs), clean up steps, chromatographic separations, and MS analysis [46]. We tested therefore the ELVIS probe for pesticide detection for a real case of sudden bee mortality using a single deceased honeybee. The ELVIS(+)‐MS, due to high matrix complexity, was noisy and complex (not shown) but a detectable pair of 35Cl/37Cl‐isotopologue ions of m/z 256.070/258.068 well above S/N and corresponding to the protonated molecule of imidacloprid, a common pesticide, could be unequivocally noted. To confirm its detection, linear ion trap MS/MS for the ion of m/z 256 was collected (Figure 10). Indeed, the known dissociation chemistry expected for the protonated imidacloprid of m/z 256 with a series of characteristic fragment ions was obtained [47].

FIGURE 10.

FIGURE 10

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ELVIS(+)‐MS/MS for the 35Cl‐isotopologue ion of m/z 256 directly detected in a wing of a single deceased honeybee suspected of being killed due to a real case of pesticide poisoning.

4. Comparing the Elvis Probe With Other MS Probes

The ELVIS Probe described and tested herein, using the simplest possible laser source, an inexpensive, relatively safe (IIIB/light IV class) laser pointer and an easy‐to‐construct Venturi pump assembled from common laboratory parts, has been therefore found to offer a simple, low‐cost, yet effective LD(A) interface for ambient MS that can be coupled to ESI and possibly to most, if not all atmospheric‐pressure ionization sources. The ELVIS probe also allows remote and gentle LD(A) without compromising sensitivity due to the reduced plume dispersion provided by Venturi pumping. Due to the advantages of LD(A) for some specific matrices, particularly its reasonably sharp spatial resolution on the order of 2 mm and deeper matrix penetration as compared to the desorption processes occurring during spray‐based or liquid‐extraction‐based techniques, as well as its improved thermal desorption efficiency for less volatile analytes, the ELVIS probe contributes to increasing the versatility of ambient MS.

Although in this exploratory study we did not extensively assess some of the important features of merits for the ELVIS probe such as reproducibility, limits of detection, depth of penetration per shot, or quantitative performance, the preliminary results consistently allow us to assume that the ELVIS probe offers a versatile and comprehensive platform for ambient MS. We arbitrarily selected and tested several proof‐of‐concept applications, but other advantageous applications of the ELVIS probe can also be envisaged. Its flexibility is also high since the probe can be manually operated with great ease and pointed even to hard‐to‐access areas on the matrix surface. The ELVIS probe can probably also be interfaced to several other ionization sources such as APCI or APPI. The Venturi effect, and thus its plume‐suction power, can also be adjusted by controlling the N2 flow for optimal sensitivity (signal‐to‐noise ratio). We used a 0.5‐W laser pointer, but similar portable laser pointers with powers up to 10 W are available.

Particularly attractive is the possibility to use the ELVIS probe in an “inverted” V‐EASI mode with liquid in/gas out (Figure 11), to benefit from the Venturi effect both for suction as well as for sonic spray ionization. In this doubly Venturi‐assisted configuration, a high‐pressure solvent could be pumped through the Venturi device to create proper vacuum that would provide proper suction of the laser plume, in a design similar to the old‐fashioned Venturi‐based water aspirators used in chemistry labs for vacuum filtration. Proper mixing of the gaseous laser plume with the high‐pressure solvent would create sonic spraying for fully voltage‐free ionization. We are currently pursuing the goal of optimizing the ELVIS probe to operate under this unique voltage‐free doubly Venturi‐assisted mode.

FIGURE 11.

FIGURE 11

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General schematic of the ELVIS probe that illustrates its potential use in a dual Venturi‐assisted mode, that is, in combination with “inverted” voltage‐free V‐EASI.

Knowing its major characteristics and performance, we can now compare the ELVIS probe with other similar and typical handheld probes in a set of techniques that, we argue, encompass a new field in ambient MS, that is, that of “probe MS.” For this comparison, we selected three major handheld probes (from indeed a diverse group) currently available for ambient MS. In Figure 12, we have attempted to represent these probes as closely as possible to their reported designs.

FIGURE 12.

FIGURE 12

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Four of the most typical devices for probe mass spectrometry.

In REIMS (Rapid Evaporative Ionization Mass Spectrometry) [48], also known as the iKnife (Figure 12A), the vapor produced during electrosurgical tissue cutting is aspirated by a Venturi pump installed in the ion source region (we found no reported details of its design) and transferred directly into the heated inlet capillary of a mass spectrometer. Ion formation in REIMS is still not completely understood but is believed to occur partially during tissue heating via droplet‐assisted desolvation by V‐EASI and additional “inlet ionization” occurring when the plume reaches the heated capillary. We argue that Venturi pumping is beneficial in REIMS because it promotes efficient plume aspiration, but since the REIMS ionization processes appear to be less efficient than those of ESI, for instance, great amounts of vapor must be generated by the electrosurgical probe. This need for excess vapor causes extensive thermal damage to the matrix, typically a tissue sample, likely resulting in significant carry overs.

In picosecond infrared laser mass spectrometry (PIRL‐MS) [49], laser ablation is performed at a wavelength of 3000 ± 100 nm using ~250 mW of power delivered through the tip of a 2‐m‐long flexible multimode sapphire fiber with a core diameter of 425 μm (Figure 12B). The fiber is coupled to a commercial solid‐state picosecond mid‐IR laser operating at 1 kHz with a pulse duration of 300 ± 100 ps. As in REIMS, ionization in PIRL‐MS appears to rely primarily on rapid matrix‐plus‐analyte evaporation and subsequent “inlet ionization,” but plume aspiration is not assisted by any dedicated device and solely relies on the vacuum suction from the inlet capillary. We therefore suspect that large amounts of vapor may also be produced through continuous laser pulsing to compensate for the relatively low ionization efficiency, which may contribute to carryovers and tissue damage. A 250‐mW mid‐IR laser (invisible to human eyes) operating near 3 μm is also capable of causing eye injuries and should be treated as a hazard Venturi‐Laser Probe rather than as an inoffensive handheld laser pointer.

As we mentioned already, the MasSpec Pen (Figure 12D) is limited to analytes that are soluble in water or organic solvents such as methanol and acetonitrile, and to target molecules located on or near the sample surface, such as for wood phytomarkers [50]. It also requires a solvent delivery pump, an electronic control circuitry installed in a controller interface that mounts to the mass spectrometer to adjust the delivery of solvent and air, and gates to regulate extraction time. But, in contrast and clear advantage, the MasSpec Pen causes neither thermal nor laser ablation, operating instead through a gentle, essentially non‐destructive and inoffensive live‐friendly liquid (pure water) extraction process, making it particularly suitable for reproducible [51] in vivo tissue analysis and for other non‐destructive analysis. The MasSpec Pen also relies largely on relatively inefficient “inlet ionization,” but the substantial volume of solvent used to transport analytes and the newly implemented heated capillary [52] to improve ionization via faster water evaporation (Figure 11D) seems to generate sufficient ion current to provide adequate sensitivity. Carryover is always an important concern in systems based on solvent transport, but disposable MasSpec pens have been employed to mitigate this effect. For similar probes based on liquid extraction, a MasSpec pen‐like probe called LEP (Liquid Extraction pen) directly coupled to an ESI source has been developed [53], as well as a 3‐in‐1 hand‐held probe combining DESI, easy ambient sonic‐spray ionization (EASI) and low‐temperature plasma (LTP) with the ion transfer tube also directly connected to the heated capillary of a mass spectrometer [54]. A hand held LD(A) probe somewhat similar to PIRL‐MS known as SpiderMass [55] has also been proposed. It uses a highly precise but equally expensive and complex medical‐grade IR laser (~2.94 μm) tuned for water excitation. It is also directly connected to the inlet capillary of the mass spectrometer relying both on vapor suction from the instrument vacuum and inlet ionization. Since it targets water excitation (resonant ablation), the SpiderMass probe is more suitable for water‐rich biological tissues but should be significantly less efficient for dehydrated samples. The SpiderMass UV laser is also invisible to the human eye, and its laser pulse can reach up to megawatts of power.

We therefore argue that the handheld ELVIS probe (Figure 12C) compares favorably with both laser‐desorption handheld systems, REIMS and PIRL‐MS (SpiderMass). The ELVIS probe employs a much simpler, less expensive, and reasonably safe “light IV class” laser pointer together with an easy‐to‐construct Venturi device assembled from common laboratory components that greatly assists and controls plume aspiration. In terms of simplicity, the ELVIS probe requires no extra control units and can also be attached to most, if not all, atmospheric‐pressure ionization sources, as we have demonstrated in this proof‐of‐concept study for ESI. The ELVIS probe also seems to enable remote gentle laser desorption without compromising sensitivity due to the reduced plume dispersion provided by its tip design and efficient Venturi‐assisted aspiration. Its greater matrix penetration compared with spray or liquid‐extraction approaches, together with its improved thermal desorption efficiency for less volatile analytes, also suggests that the ELVIS probe significantly expands the versatility and applicability of “probe MS.”

The very low amount of vapor produced by laser desorption by the Venturi‐assisted ELVIS probe also minimizes carryovers. In fact, we have sequentially used the probe many times for different samples, noting no detectable carryovers. Probably therefore, less volatile analytes that could cause more severe carryovers condense in the probe tip or in its transfer tube never reaching the ESI source. These vapors would also only accumulate to produce background signals after much prolonged use. But for precaution, from sample to sample, we washed the tip, transfer tube, and Venturi pump with water and methanol. For this proof‐of‐principle study, we used a 0.5‐W laser pen, but for more demanding matrices, laser pointers with powers up to 10 W are available and could be tested.

5. Conclusions

In all, we have demonstrated the efficient design for molecular analysis of a small, simple, inexpensive, considerable safe yet considerably powerful 0.5‐W laser pointer able to perform laser desorption coupled to ESI. While the MasSpec Pen using gentle, inoffensive and live‐friendly water extraction seems unbeatable particularly for in vivo tissue analysis, the ELVIS probe seems particularly advantageous for its greatest simplicity (the simplest among all handheld MS probes so far reported) and for target analytes more deeply embedded within their matrices. It therefore seems that the MasSpec Pen and the ELVIS probe could form a powerful duo for most comprehensive “probe mass spectrometry.”

Funding

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, and Mackpesquisa.

Acknowledgments

We thank the Brazilian research agencies CNPq, CAPES, ANP, FAPESP, and MACKPESQUISA for financial assistance. This paper is dedicated to R.G. Cooks for his intensive, pioneering, and inspiring work in ambient MS, particularly for inspiring mass spectrometrists to use the unbeatable power of MS in clinical and medical applications.

Contributor Information

Clécio Fernando Klitzke, Email: clecio1965@gmail.com.

Marcos N. Eberlin, Email: marcos.eberlin@mackenzie.br.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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