Abstract
The serious impact of the Covid-19 pandemic underscores the need for rapid, reliable, and high-throughput diagnosis methods for infection. Current analytical methods, either point-of-care or centralized detection, are not able to satisfy the requirements of patient-friendly testing, high demand, and reliability of results. Here, we propose a two-point separation on-demand diagnostic strategy that uses laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF MS) and adopts a stable yet cleavable ionic probe as a mass reporter. The use of this reporter enables ultrasensitive, interruptible, storable, restorable, and high-throughput on-demand detection. We describe a demonstration of the concept whereby we (i) design and synthesize a laser-cleavable reporter (DTPA), (ii) conjugate the reporter onto an antibody and verify the function of the conjugate, (iii) detect with good turnaround and high sensitivity the conjugated reporter, (iv) analyze quantitatively by using a laser-cleavable internal standard, and (v) identify negative and positive samples containing the spike protein. The protocol has excellent sensitivity (amol for the SARS-CoV-2 Spike S1 subunit antibody) without any amplification. This strategy is also applicable for the detection of other disease antigens besides SARS-CoV-2.
| Original language | English |
|---|---|
| Pages (from-to) | 12-17 |
| Number of pages | 6 |
| Journal | Analytical Chemistry |
| Volume | 96 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 9 2024 |
| Externally published | Yes |
Funding
This work was supported by grants from Advanced Therapy Product Consulting, J.C.B.’s Fellowship for Science and Engineering from the David and Lucile Packard Foundation, and the NIH (R24GM136766 to M.L.G.). The authors are grateful to Protein Metrics for software.
