Tissue on paper: Direct mass spectrometry of biopsy samples

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  • Published: Feb 1, 2011
  • Author: Steve Down
  • Channels: Base Peak
thumbnail image: Tissue on paper: Direct mass spectrometry of biopsy samples

Paper spray mass spectrometry: an easy ambient technique

In 2010, paper spray ionisation was announced as one of the new generation of ambient mass spectrometry techniques, in which ionisation takes place in the open air. These techniques all profit from a minimum of sample preparation, if any at all, and can provide mass spectra within a few seconds.

Paper spray differs from most of the related ambient methods by operating successfully without the need for a sheath liquid or sheath gas. Sample is loaded onto a small piece of triangular paper, wetted with solvent, then held with the point facing the mass spectrometer inlet while a high voltage of several kV is applied to the paper.

The high electric potential between the paper and the mass spectrometer inlet is believed to induce charges that accumulate at the paper apex, subsequently forming charged droplets. These desolvate to produce bare ions which are drawn into the mass spectrometer.

The paper triangle is quite small with a base width of 5 mm and a height of 10 mm and its position relative to the inlet is not critical. The technique has been demonstrated for a range of standard compounds such as drugs, amino acids, fatty acids, peptides, proteins and pesticides.

Biological fluids like urine and blood have also been analysed but one of the key targets is the direct analysis of biological tissue, which has been successfully achieved by several other ambient mass spectrometry techniques.

Now, scientists from Purdue University, where developed paper spray mass spectrometry was developed, have extended its scope to the analysis of biological tissue, as described by principal reporter Zheng Ouyang.

Biopsies on paper: hormones, lipids and drugs detected

Several different types of tissue were analysed to illustrate the types of analyses that can be carried out. They were obtained by homogenising various organs of the rat and by taking samples of other tissues by punch biopsy or needle aspiration biopsy. Some analyses were conducted by smearing a section of tissue on a glass slide.

For the analysis of hormones, a biopsy sample of porcine adrenal gland about 1 mm3 was placed in the middle of a piece of grade I chromatography paper and sprayed with aqueous methanol. On application of a high voltage, the positive-ion mass spectrum clearly showed peaks corresponding to the protonated molecules of epinephrine and norepinephrine which were confirmed by tandem mass spectrometry.

Lipids were analysed in human prostate tumour and adjacent normal tissue by taking 1 mm2 x 15 µm thick samples from tissue sections and smearing them onto the paper surface. These are basic sample preparation conditions but they produced acceptable results.

The overall signal intensities were higher than those from typical DESI mass spectra of the same tissue, which the team attributed to the longer solvent extraction times and volumes adopted in paper spray.

In positive mode, the signal intensity for phosphatidylcholine-34:1 was markedly higher in diseased tissue than normal tissue, whereas those for various sphingomyelin species were reduced, both good markers for tumour detection and checking tumour margins.

Rat brain samples from the white and grey matter regions were taken with a metal needle and analysed in negative-ion mode. Phosphatidylserine-40:6 was more abundant in the grey matter whereas sulphatide-24:1 was more dominant in the white matter, in agreement with published DESI imaging MS results from the Cooks group at Purdue University.

The detection of therapeutic drugs in spiked tissues was also demonstrated for atenolol and imatinib. This is an important consideration for drug testing, since blood levels do not necessarily correlate with concentrations at the target site or at other organs where side effects might occur.

The quantitative ability of paper spray mass spectrometry was illustrated with the analysis of several homogenised rat organs following the administration of hydralazine. A calibration curve was prepared from undoped rat tissue that was spiked with known amounts of the drug and used to calculate the drug concentration in kidney homogenate as 4.2 µg/g.

However, analysis of the bulk kidney tissue produced a mass spectral signal that was lower for the homogenate. The difference was attributed to differences in extraction efficiencies of the drug during solvent spraying, that from the homogenate being about ten-fold higher than from the bulk tissue.

The team also found that the tissue matrix and the amount of tissue homogenate also affected the signals. These factors demonstrate the work that must still be done for accurate and consistent quantitative results.

However, in general, paper spray mass spectrometry offers a rapid and convenient method for the analysis of tissue biopsies, clearing the way for point-of-care diagnostics and fast screening in clinics. It could also be used in operating theatres to help confirm that surgeons have removed tumours in their entirety.

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

The recently developed ambient technique known as paper spray mass spectrometry has been extended to the direct analysis of biological tissue from biopsies, detecting hormones, lipids and drugs within 1 minute from small samples.
Paper spray mass spectrometry (Click on image for a larger view)
Image courtesy Ouyang Research Group, Purdue University
Zheng Ouyang

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