A chemical printing method based on gold nanoparticle (AuNP)-assisted laser ablation has been developed. By rastering a thin layer of AuNPs coated on a rat kidney tissue section with a UV laser, biomolecules are extracted and immediately transferred/printed onto a supporting glass substrate. The integrity of the printed sample is preserved, as revealed by imaging mass spectrometric analysis. By studying the mechanism of the extraction/printing process, transiently molten AuNPs were found to be involved in the process, as supported by the color and morphological changes of the AuNP thin film. The success of this molecular printing method was based on the efficient laser–nanomaterial interaction, that is, the strong photoabsorption, laser-induced heating, and phase-transition properties of the AuNPs. It is anticipated that the molecular printing method can be applied to perform site-specific printing, which extracts and transfers biochemicals from different regions of biological tissue sections to different types of supporting materials for subsequent biochemical analysis with the preservation of the original tissue samples.Topics: Biochemical analysis; Biochemistry; Extraction; Heat transfer; Heat transfer; Mass spectrometry; Nanoparticles; Phase transition; Surface treatment;

Systematically controlling heat transfer in the surface-assisted laser desorption/ionization (SALDI) process and thus enhancing the analytical performance of SALDI-MS remains a challenging task. In the current study, by tuning the metal contents of Ag–Au alloy nanoparticle substrates (AgNPs, Ag55Au45NPs, Ag15Au85NPs and AuNPs, ∅: ∼2.0 nm), it was found that both SALDI ion-desorption efficiency and heat transfer can be controlled in a wide range of laser fluence (21.3 mJ cm−2 to 125.9 mJ cm−2). It was discovered that ion detection sensitivity can be enhanced at any laser fluence by tuning up the Ag content of the alloy nanoparticle, whereas the extent of ion fragmentation can be reduced by tuning up the Au content. The enhancement effect of Ag content on ion desorption was found to be attributable to the increase in laser absorption efficiency (at 355 nm) with Ag content. Tuning the laser absorption efficiency by changing the metal composition was also effective in controlling the heat transfer from the NPs to the analytes. The laser-induced heating of Ag-rich alloy NPs could be balanced or even overridden by increasing the Au content of NPs, resulting in the reduction of the fragmentation of analytes. In the correlation of experimental measurement with molecular dynamics simulation, the effect of metal composition on the dynamics of the ion desorption process was also elucidated. Upon increasing the Ag content, it was also found that phase transition temperatures, such as melting, vaporization and phase explosion temperature, of NPs could be reduced. This further enhanced the desorption of analyte ions via phase-transition-driven desorption processes. The significant cooling effect on the analyte ions observed at high laser fluence was also determined to be originated from the phase explosion of the NPs. This study revealed that the development of alloy nanoparticles as SALDI substrates can constitute an effective means for the systematic control of ion-desorption efficiency and the extent of heat transfer, which could potentially enhance the analytical performance of SALDI-MS.

Metal alloy nanoparticles (NPs) offer a new combination of unique physicochemical properties based on their pure counterparts, which can facilitate the development of novel analytical methods. Here, we demonstrated that Ag–Au alloy NPs could be utilized for optical and mass spectrometric imaging of latent fingerprints (LFPs) with improved image contrast, stability, and detection sensitivity. Upon deposition of Ag–Au alloy NPs (Ag:Au = 60:40 wt %), ridge regions of the LFP became amber colored, while the groove regions appeared purple-blue. The presence of Au in the Ag–Au alloy NPs suppressed aggregation behavior compared to pure AgNPs, thus improving the stability of the developed LFP images. In addition, the Ag component in the Ag–Au alloy NPs enhanced optical absorption efficiency compared to pure AuNPs, resulting in higher contrast LFP images. Moreover, varying the Ag–Au ratio could enable the tuning of the resulting surface plasmonic resonance absorption and hence affect image contrast. Furthermore, the Ag–Au alloy NPs assisted the surface-assisted laser desorption/ionization MS analysis of chemical and biochemical compounds in LFPs, with better detection sensitivity than either pure AgNPs or AuNPs.Keywords: image contrast; image stability; latent fingerprints; nanoalloys; SALDI-MS; silver−gold nanoparticles

•UV-absorbing AuNPs coating enables direct LDI-MS analysis for OTC Drugs and CCM granules.•IR-transparent AuNPs coating allows standard FT-IR screening of major drug ingredients.•Quantification of phytochemical marker compounds in CCM granules was achieved, with LOD down to nanogram level.With a coating of gold nanoparticles (AuNPs), over-the-counter (OTC) drugs and Chinese herbal medicine granules in KBr pellets could be analyzed by Fourier Transform Infra-red (FT-IR) spectroscopy and Surface-assisted Laser Desorption/Ionization mass spectrometry (SALDI-MS). FT-IR spectroscopy allows fast detection of major active ingredient (e.g., acetaminophen) in OTC drugs in KBr pellets. Upon coating a thin layer of AuNPs on the KBr pellet, minor active ingredients (e.g., noscapine and loratadine) in OTC drugs, which were not revealed by FT-IR, could be detected unambiguously using AuNPs-assisted LDI-MS. Moreover, phytochemical markers of Coptidis Rhizoma (i.e. berberine, palmatine and coptisine) could be quantified in the concentrated Chinese medicine (CCM) granules by the SALDI-MS using standard addition method. The quantitative results matched with those determined by high-performance liquid chromatography with ultraviolet detection. Being strongly absorbing in UV yet transparent to IR, AuNPs successfully bridged FT-IR and SALDI-MS for direct analysis of active ingredients in the same solid sample. FT-IR allowed the fast analysis of major active ingredient in drugs, while SALDI-MS allowed the detection of minor active ingredient in the presence of excipient, and also quantitation of phytochemicals in herbal granules.

The phase transition of surface-assisted laser desorption/ionization (SALDI) substrates has been identified as a driving process for ion desorption in many previous SALDI fundamental studies. Here, the effects of various phase transition stages, including substrate melting, vaporization, and phase explosion, on SALDI ion desorption efficiency and extent of heat transfer were investigated. We employed molecular dynamics to simulate the phase transition (from melting, vaporization, to phase explosion) of gold nanoparticles (AuNPs, ⌀: 2.5 nm) upon laser-induced heating and experimentally probed the corresponding SALDI ion desorption efficiency and extent of heat transfer to a chemical thermometer, benzylpyridinium (BP) salt (using 355 nm solid-state laser, pulse width: 6 ns, laser fluence range: 21.3 to 125.9 mJ/cm2). The results showed that substrate phase explosion has the most significant effect on enhancing the ion desorption efficiency and lowering the extent of heat transfer, which were reflected by an abrupt increase in both the ion desorption efficiency and the survival yield, when the laser fluence exceeded the AuNPs’ phase explosion threshold temperature (5800 K). Compared with phase explosion, vaporization only exhibited a limited effect on the ion desorption efficiency, while the effect of melting was not noticeable and even overridden by the thermal-driven desorption. The significant effect of phase explosion on enhancing the ion desorption efficiency could be attributed to the weaker binding interaction between the BP ions and the Au atoms which were rapidly ablated during the phase explosion stage, and the cooling effect on the BP ions could be due to the adiabatic expansion of the ablation plume during the phase explosion. The study revealed that the SALDI substrate with a lower phase explosion threshold would have a higher potential in enhancing the analytical performance of SALDI-MS.

Fundamental factors governing the ion-desorption efficiency and extent of internal-energy transfer to a chemical thermometer, benzylpyridinium ion ([BP]+), generated in the surface-assisted laser desorption/ionization (SALDI) process, were systematically investigated using noble metal nanoparticles (NPs), including AuNPs, AgNPs, PdNPs, and PtNPs, as substrates, with an average particle size of 1.7–3.1 nm in diameter. In the correlation of ion-desorption efficiency and internal-energy transfer with physicochemical properties of the NPs, laser-induced heating of the NPs, which are dependent on their photoabsorption efficiencies, was found to be a key factor in governing the ion-desorption efficiency and the extent of internal-energy transfer. This suggested that the thermal-driven desorption played a significant role in the ion-desorption process. In addition, a stronger binding affinity of [BP]+ to the surface of the NPs could hinder its desorption from the NPs, and this could be another factor in determining the ion-desorption efficiency. Moreover, metal NPs with lower melting points could also facilitate the ion-desorption process via the phase-transition process, which could lower the activation barrier (ΔG#) of the ion-desorption process by increasing the entropic change (ΔS#). The study reveals that high photoabsorption efficiency, weak binding interaction with analyte molecule, and low melting point could be critical for the design of SALDI substrates with efficient ion desorption.

The simplicity and easy manipulation of a porous substrate-based ESI-MS technique have been widely applied to the direct analysis of different types of samples in positive ion mode. However, the study and application of this technique in negative ion mode are sparse. A key challenge could be due to the ease of electrical discharge on supporting tips upon the application of negative voltage. The aim of this study is to investigate the effect of supporting materials, including polyester, polyethylene and wood, on the detection sensitivity of a porous substrate-based negative ESI-MS technique. By using nitrobenzene derivatives and nitrophenol derivatives as the target analytes, it was found that the hydrophobic materials (i.e., polyethylene and polyester) with a higher tendency to accumulate negative charge could enhance the detection sensitivity towards nitrobenzene derivatives via electron-capture ionization; whereas, compounds with electron affinities lower than the cut-off value (1.13 eV) were not detected. Nitrophenol derivatives with pKa smaller than 9.0 could be detected in the form of deprotonated ions; whereas polar materials (i.e., wood), which might undergo competitive deprotonation with the analytes, could suppress the detection sensitivity. With the investigation of the material effects on the detection sensitivity, the porous substrate-based negative ESI-MS method was developed and applied to the direct detection of two commonly encountered explosives in complex samples.

A new ambient ionization method allowing the direct chemical analysis of living human body by mass spectrometry (MS) was developed. This MS method, namely Megavolt Electrostatic Ionization Mass Spectrometry, is based on electrostatic charging of a living individual to megavolt (MV) potential, illicit drugs, and explosives on skin/glove, flammable solvent on cloth/tissue paper, and volatile food substances in breath were readily ionized and detected by a mass spectrometer.

Direct chemical analysis and molecular imaging of questioned documents in a non/minimal-destructive manner is important in forensic science. Here, we demonstrate that solvent-free gold-nanoparticle-assisted laser desorption/ionization mass spectrometry is a sensitive and minimal destructive method for direct detection and imaging of ink and visible and/or fluorescent dyes printed on banknotes or written on questioned documents. Argon ion sputtering of a gold foil allows homogeneous coating of a thin layer of gold nanoparticles on banknotes and checks in a dry state without delocalizing spatial distributions of the analytes. Upon N2 laser irradiation of the gold nanoparticle-coated banknotes or checks, abundant ions are desorbed and detected. Recording the spatial distributions of the ions can reveal the molecular images of visible and fluorescent ink printed on banknotes and determine the printing order of different ink which may be useful in differentiating real banknotes from fakes. The method can also be applied to identify forged parts in questioned documents, such as number/writing alteration on a check, by tracing different writing patterns that come from different pens.

Latent fingerprint (LFP) detection is a top-priority task in forensic science. It is a simple and effective means for the identification of individuals. Development of nanomaterials which maximize the surface interaction with endogenous substances on the ridges to enhance the contrast of the fingerprints is an important application of nanotechnology in LFP detection. However, most developments in this area have mainly focused on the visualization of the physical pattern of the fingerprints and failed to explore the molecular information embedded in LFPs. Here, we have integrated certain distinctive properties of gold nanoparticles (AuNPs) with imaging mass spectrometry for both the visualization and molecular imaging of LFPs. Two contrasting colors (blue and pink), arising from different surface plasmon resonance (SPR) bands of the AuNPs, reveal the optical images of LFPs. The laser desorption/ionization property of the AuNPs allows the direct analysis of endogenous and exogenous compounds embedded in LFPs and imaging their distributions without disturbing the fingerprint patterns. The simultaneous visualization of LFP and the recording of its molecular images not only provide evidence on individual identity but also resolve overlapping fingerprints and detect hazardous substances.

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) was applied to the direct analysis of melamine cyanurate (MC). The three commonly used MALDI matrixes, namely, α-cyano-4-hydroxycinnamic acid (CHCA), sinapinic acid (SA), and 2,5-dihydroxybenzoic acid (DHB), were able to desorb/ionize melamine from MC upon N2 laser irradiation, with CHCA showing the highest detection sensitivity in the positive mode. Only DHB and SA were able to desorb/ionize cyanuric acid from MC in the negative mode but with remarkably lower sensitivity. The method is able to detect melamine unambiguously from a small amount of MC (down to 12.5 μg) spiked into urine and was successfully applied for the rapid and sensitive detection of melamine in urine stones/residues of the samples collected from patients clinically confirmed of having kidney stones associated with the consumption of melamine-tainted food products. The urine matrix resulted in interfering ion peaks and suppressed the ion intensity of melamine, while a cleanup process consisting of simply washing with water eliminated such interference and enhanced the ion intensity. The merit of the method is simplicity in sample preparation. The analytical time of the method for high-throughput analysis from the time of sample treatment to analysis is less than 7 minutes per sample, with sensitive detection of the presence of melamine in the urine stones/residues of the patient samples.

Ion desorption efficiency and internal energy transfer were probed and correlated in carbon-based surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) using benzylpyridinium (BP) salt as the thermometer chemical. In a SALDI-MS experiment with a N2 laser (at 337 nm) used as the excitation light source and with multiwalled carbon nanotubes (CNT), buckminsterfullerene (C60), nanoporous graphitic carbon (PGC), non-porous graphite particles (G), highly oriented pyrolytic graphite (HOPG), or nanodiamonds (ND) as the SALDI substrate, both the desorption efficiency in terms of ion intensity of BP and the extent of internal energy transfer to the ions are dependent on the type and size of the carbon substrates. The desorption efficiency (CNT ∼ C60 > PGC > G > HOPG > ND) in general exhibits an opposite trend to the extent of internal energy transfer (CNT < C60 ∼ PGC < G ∼ HOPG < ND), suggesting that increasing the extent of internal energy transfer in the SALDI process may not enhance the ion desorption efficiency. This phenomenon cannot be explained by a thermal desorption mechanism, and a non-thermal desorption mechanism is proposed to be involved in the SALDI process. The morphological change of the substrates after the laser irradiation and the high initial velocities of BP ions (1100−1400 ms−1) desorbed from the various carbon substrates suggest that phase transition/destruction of substrates is involved in the desorption process. Weaker bonding/interaction and/or a lower melting point of the carbon substrates favor the phase transition/destruction of the SALDI substrates upon laser irradiation, consequently affecting the ion desorption efficiency.