Direct Analysis of Biofluids by Mass Spectrometry with Microfluidic Voltage-Assisted Liquid Desorption Electrospray Ionization

Abstract

Signal suppression by sample matrix in direct electrospray ionization -mass spectrometric (ESI-MS) analysis hampers its clinical and biomedical applications. We report herein the development of a microfluidic voltage-assisted liquid desorption electrospray ionization (VAL-DESI) source to overcome this limitation. Liquid DESI is achieved for the first time in a microfluidic format. Direct analysis of urine, serum, and cell lysate samples by using the proposed microfluidic VAL-DESI-MS/MS method to detect chemical compounds of biomedical interest, including nucleosides, monoamines, amino acids, and peptides is demonstrated. Analyzing a set of urine samples spiked with dihydroxyphenylalanine (DOPA) showed that the assay had a linear calibration curve with r2 value of 0.997 and a limit of detection of 0.055 μM DOPA. The method was applied to simultaneous quantification of nucleosides, i.e. cytidine, adenosine, uridine, thymidine, and guanosine in cell lysates using 8-bromoadenosine as internal standard. Adenosine was found most abundant at 26.5 ± 0.57nmole/106 cells while thymidine was least at 3.1 ± 0.31nmole/106 cells. Interestingly, the ratio of adenosine to deoxyadenosine varied significantly from human red blood cells (1.07 ± 0.06) to cancerous cells, including lymphoblast TK6 (0.52 ± 0.02), skin melanoma C32 (0.82 ± 0.04), and promyelocytic leukemia NB4 cells (0.38 ± 0.06). These results suggest that the VAL-DESI-MS/MS technique has a good potential in direct analysis of biofluids. Further, due to the simplicity in its design and operation, the proposed microfluidic liquid DESI source can be fabricated as a disposable device for point-of-care measurements.

On-chip mass spectrometric analysis in non-polar solvents by liquid beam infrared matrix-assisted laser dispersion/ionization

“…To overcome this limited application range, ESI has been the subject of intensive research [27]. Approaches described in the literature include atmospheric pressure chemical ionization (APCI) [28][29][30][31], atmospheric pressure photoionization (APPI), solvent-assisted electrospray ionization (SAESI) [32][33][34][35], desorption electrospray ionization (DESI) [36][37][38], easy ambient spray ionization (EASI) [39][40][41][42][43], laser ablation electrospray ionization (LAESI) [44], and low-temperature plasma ionization (LTP) [45]. There are practically no literature reports on direct mass spectrometric on-chip analysis of compounds dissolved in water non-miscible, non-polar solvents.…”

Fabricating an Electrospray Ionization Chip Based on Induced Polarization and Liquid Splitting

“…The coupling of the microfluidic chip to mass spectrometry (Chip–MS) can greatly broaden the application fields of microfluidics technology and MS [ 11 , 12 , 13 , 14 ]. In Chip–MS analysis, many functions, such as separation, extraction, desalination, ionization, and so on, can be integrated on one microfluidic chip to simplify the experimental procedure, reduce the detection time, and facilitate the analysis of limited-quantity samples [ 15 , 16 , 17 , 18 ]. Moreover, a miniature mass spectrometer coupled with a microfluidic sample processing device is likely to become a powerful tool for field applications.…”

Fast and facile preparation of nanostructured silicon surfaces for laser desorption/ionization mass spectrometry of small compounds

“…Noteworthy, both qualitative and quantitative measurements are feasible provided that adequate experimental conditions are satisfied. Other efficient mass spectrometric based approaches have been reported for biofluids analysis such as time‐of‐flight secondary ion mass spectrometry (TOF‐SIMS), desorption electrospray ionization (DESI)‐MS or direct analysis in real time (DART), to name but a few . Nevertheless, in contrast to such mainstream analytical methods, we have already investigated, as have others, inert substrates to replace conventional organic matrices to promote ion formation in so‐called surface‐assisted laser desorption/ionization mass spectrometry (SALDI‐MS) .…”