Real-Time Molecular Diagnosis of Tumors Using Water-Assisted

Laser Desorption/Ionization Mass Spectrometry Technology

 How Cancer is Diagnosed?

1. Final diagnosis is established based on the histological examination of a tissue specimen, which is obtained via core biopsy, endoscopic
punch biopsy, or surgical biopsy using laparoscopy or laparotomy.

2. However, In these lesions rapid, accurate, or precise diagnosis based on morphology and routine ancillary techniques can be
challenging. There is, thus, an ample need for a molecular technique that could improve and expedite diagnostic
decisions. Ideally, a device that can provide instant diagnosis
Real-Time Molecular Diagnosis of Tumors Using Water-Assisted Laser
Desorption/Ionization Mass Spectrometry Technology (SpiderMass)

SpiderMass

Why is it necessary to develop a real-time diagnostic system?

The real-time diagnosis will allow the surgeon to accurately define the tumor margins thereby defining its excision
margins while avoiding the removal of healthy tissues in surgery https://www.nature.com/articles/s41596-019-0217-8
Water-Assisted Laser Desorption/Ionization - Time of Flight Mass Spectrometry
Technology (WALDI- TOF) - Theory

WALDI ~ MALDI - TOF

Matrix-Assisted Laser Desorption/Ionization - Time of Flight Mass

Spectrometry (MALDI- TOF)
The water molecules act as an endogenous matrix in a matrix-assisted laser desorption ionization (MALDI)-like scenario
https://www.creative-proteomics.com/technology/maldi-tof-mass-spectrometry.htm
 Matrix-Assisted Laser Desorption/Ionization
Mass Spectrometry Technology (MALDI)

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KE= mv2
𝟐

https://sci-hub.se/10.1515/cclm-2012-0291
 SpiderMass: Application in cancer diagnostic

Develop the classification model

Sample preparation → Data processing → Building classification models from biopsy samples
 Develop the classification model

33 samples

Tissue processing after surgery and the analytical sequence

 Develop the classification model

Classification of normal/ tissues

The multivariate analysis using principal-component analysis (PCA) and Linear

discriminant analysis (LDA)
Cross-Validation Results Using the “Leave One Patient Out” Methods

- Excellent cross-validation results were obtained using the “leave one patient out” method with 99.94%
and 95.37% correct classification rates with and without outliers in the positive mode and 97.63% and
94.54% in the negative mode
Classification of normal, cancer, and necrosis tissues

PC-LDA Models Using a Three-Class Scheme (Normal, Cancer, and Necrosis)

Cross-Validation Results Using the “Leave One Patient Out” Methods

Leave one patient out cross-validation based on the normal/cancer/necrosis classification shows 99.06%
and 81.89% correct classification rates
 Real-Time Tissue Analysis and Classification

1. The model generated by PC-LDA for normal/cancer/necrosis classification was loaded

into the OMB-Recognition software

2. Conduct in vivo or ex vivo tests to collect MS data, the data is immediately transferred to
the software containing the classification model.

3. The readout is a prediction of the cancer, normal, and necrotic classes, which is
displayed with less than a 1-s time delay compared with spectral acquisition
 Conclusion

- SpiderMass technology enables the acquisition of histologically specific

molecular signatures (or molecular barcoding) in different sarcoma-type tumors

- The SpiderMass system can analyze directly the raw biopsy tissues and does
not require any sample processing

- Using the MS molecular profiles, classification models are created and

successfully cross-validated (cancer/normal, cancer/normal/necrotis)

- The real-time classification will allow the surgeon to accurately define the
tumor margins thereby defining its excision margins while avoiding the
removal of healthy tissues in surgery
Thank you for your attention!