Development of a disposable paper-based thin film solid-phase microextraction sampling kit to quantify ketone body†

Diabetes ketoacidosis (DKA) is a life-threatening complication and requires immediate medical attention in the case of diabetes subjects, especially in the case of type 1 diabetes mellitus. In the condition of DKA, the body produces an excess amount of ketone bodies after unregulated fat degradation, causing blood to become acidic and hampering the regular metabolic activities of the body. The current diagnostic technique for DKA condition is based on monitoring ketone bodies, especially β-hydroxybutyric acid, from human urine and blood samples. The detection of serum ketone bodies in pathology is sometimes limited due to false positive results and the lack of standardization for precise quantification of analytes. In this study, a paper-based patch operating on the thin film solid-phase microextraction (TF-SPME) principle was developed and it was coupled with gas chromatography-mass spectrometry for simple quantification of β-hydroxybutyric acid (BHB) ketone body from a phosphate-buffered saline matrix. To fabricate the paper-based TF-SPME patches, a regular A4 sheet paper sheet was utilized as the substrate and uniform coating by multiwalled carbon nanotubes (MWCNT), polydimethylsiloxane (PDMS) and divinyl benzene (DVB) compounds was performed with an automatic film applicator. The 70 μm paper-based coated sheet was trimmed into 4 cm × 1 cm dimension pieces to obtain multiple patches from a single sheet. Extraction of the BHB ketone body into the closed vials was performed by exploiting the individual DVB/PDMS and DVB/CNT/PDMS paper patches followed by desorption with acetonitrile before quantification by gas chromatography-mass spectrometry analysis. Our study showed that the BHB extraction efficiency of DVB/PDMS-coated patches was higher than that of DVB/CNT/PDMS. The outcome showed a good linearity (R² = 0.99) within the 500–20 000 ng mL⁻¹ concentration range of BHB by paper-based DVB/PDMS patches. This study demonstrated the feasibility of utilizing simple, cost-effective paper-based disposable TF-SPME patches as a sampling kit for future screening of diabetes ketoacidosis without the need for prolonged traditional sample preparation in pathology.