Tumor Cell Detection by Mass Spectrometry Using Signal Ion Emission Reactive Release Amplification

Abstract

A method is presented for the detection of circulating tumor cells (CTC) using mass spectrometry (MS), through reporter-ion amplification. Particles functionalized with short-chain peptides are bound to cells through antibody-antigen interactions. Selective release and MS detection of peptides is shown to detect as few as 690 cells isolated from a 10 mL blood sample. Here we present proof-of-concept results that pave the way for further investigations.

Enumeration of Rare Cells in Whole Blood by Signal Ion Emission Reactive Release Amplification with Same-Sample RNA Analysis

“…Applying the calculated values to eq and eq along with the computed σ 0 (1.93 × 10 –3 ) results in an LOD of ∼26 cells and an LOQ of ∼42 cells. The LOD achieved in this work represents an increase in sensitivity of approximately 10-fold when compared to previous work using SIERRA for the detection of SKBR3 cells in whole blood …”

“…Mass cytometry has demonstrated measurement of >30 markers on a single cell without chromatographic separation 32,33 but requires hundreds of cells for meaningful analysis 34 , has a recovery rate of <50% during sample pre-processing 35 , and all cellular material is destroyed during analysis. We have previously demonstrated the use of particles coupled with cleavable mass labels and detection antibodies for the non-destructive enumeration of tumor cells 36 . While effective, this method is not amenable to high-throughput screening and recovery of genetic material for analysis is cumbersome at best.…”

NIR II Light-Response Au Nanoframes: Amplification of a Pressure- and Temperature-Sensing Strategy for Portable Detection and Photothermal Therapy of Cancer Cells

“…At the same time, the increase in temperature also showed a good linear relationship with the cell number in the range from 10 and 10 5 cells/mL (Figure D), and the LOD was calculated to be as low as 5 cells/mL. The LODs of these two modes were far lower than those reported by previous test methods based on electrochemistry, , mass spectrometry, , and optics …”

“…At the same time, the increase in temperature also showed a good linear relationship with the cell number in the range from 10 and 10 5 cells/mL (Figure 3D), and the LOD was calculated to be as low as 5 cells/mL. The LODs of these two modes were far lower than those reported by previous test methods based on electrochemistry, 5,8 mass spectrometry, 20,21 and optics. 25 Finally, to prove potential clinical applications of the Au NFbased pressure-and temperature-sensing strategy, HeLa cells were spiked into human serum and human blood diluted 1000 times to simulate real samples.…”

“…The development of an ultrasensitive and selective method for detecting cancer cells is very important for the early diagnosis and timely prognosis of cancer. − However, the level of cancer cells in the early biological system is extremely low and cannot be detected by conventional methods. To date, a variety of cancer cell detection methods based on different readout techniques, such as electrochemical, − fluorescent, − chemiluminescent, , magnetic, , Raman, − mass spectrometry, − microfluidic, , and colorimetric measurements, − have been developed. Although these detection methods can achieve accurate and highly sensitive detection of cancer cells, they are costly, operate complicatedly, and require large-scale dedicated instruments, which seriously confine their utility in the fieldwork or specific point-of-care testing.…”