Blood Test on a Chip Offers Low-Cost Lung Cancer Detection Without DNA Sequencing

Lung cancer is the leading cause of cancer deaths worldwide, and screening often yields indeterminate results that prompt invasive workups. Computed tomography (CT) detects small nodules but can flag benign findings, adding patient risk and cost. Liquid biopsies offer a noninvasive alternative but typically depend on DNA sequencing and complex analytics. A new study shows a sequencing-free blood test on a chip can classify lung cancer using chemical fingerprints in cell-free DNA.

Tel Aviv University scientists developed a method called sequencing-free on‑chip detection by fluorescent enzymatic profiling of cell‑free DNA (cfDNA) methylation. After extracting cfDNA from blood, the fragments are labeled with a light‑emitting marker and hybridized to a custom DNA chip. An optical scanner reads the chip, and light‑emission patterns are computationally analyzed to identify a malignancy‑specific chemical signature, eliminating the need for DNA sequencing.

In a study of 103 participants, the cohort comprised 51 individuals with lung cancer and 52 healthy controls. Following a training phase, the team derived a signature spanning 170 genomic regions and evaluated it in a separate validation set using blinded analysis. The approach also differentiated the two predominant histologies—adenocarcinoma and squamous cell carcinoma—based on distinct cfDNA signatures.

For patients with stage 2-4 disease, the test achieved 93.1% sensitivity and 90.3% specificity. Beyond diagnosis, serial testing reflected treatment response: fingerprints in responders shifted toward a healthy profile, while non‑responders showed no meaningful change, mirroring imaging results. The investigators emphasized that these monitoring findings are preliminary and require confirmation in larger studies.

The work, published in npj Precision Oncology, involved collaborators from JaxBio Technologies, Bnai Zion Medical Center, and Sheba Medical Center. The researchers cited simplicity, low cost, and rapid turnaround as key advantages; current processing takes two to three days at an estimated cost of about $60 per sample. They indicated that the assay could complement imaging, support earlier diagnosis of lung cancer, and help monitor treatment effectiveness.

“Our goal is to make blood tests for cancer diagnosis more accessible, simpler and less expensive without compromising accuracy. We have developed a new approach that does not require genetic sequencing but instead identifies the tumor's chemical 'fingerprint' with light, using a technology that can be implemented in standard clinical laboratories. This is a significant step toward developing a tool that can complement imaging tests and help physicians diagnose lung cancer and monitor treatment effectiveness,” said Yuval Ebenstein, professor at Tel Aviv University’s School of Chemistry, Department of Biomedical Engineering, and the Zimin Institute.

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