Crispr optical blood test spots lung cancer biomarkers at near-zero levels

A new study reveals a Crispr-powered optical sensor that can detect lung cancer biomarkers at sub-attomolar levels, far earlier than conventional scans or PCR tests

A routine blood test may soon be able to detect cancer long before a tumour becomes visible on a scan.

 

Researchers have developed a highly sensitive light-based sensor capable of identifying extremely small amounts of cancer biomarkers in blood, down to sub-attomolar levels, meaning only a few molecules need to be present for detection.

 

According to the study titled Sub-Attomolar-Level Biosensing of Cancer Biomarkers Using SHG Modulation in DNA-Programmable Quantum Dots/MoS₂ Disordered Metasurfaces, published in Optica, the team, led by Han Zhang of Shenzhen University, combined DNA nanostructures, quantum dots, Crispr gene-editing tools and a nonlinear optical technique called second harmonic generation (SHG) to produce a clear diagnostic signal to detect cancer-linked microRNA in patient blood samples with greater sensitivity than conventional RT-qPCR. 

 

How this Crispr blood test differs from current cancer screening 

Most early cancer diagnostics rely on imaging or molecular amplification techniques such as RT-qPCR. Imaging detects tumours once they reach a visible size. PCR methods amplify genetic material to make it measurable. Both approaches work, but neither is ideal for detecting disease at its absolute earliest molecular stages.

 

This new system bypasses chemical amplification altogether. Instead of copying genetic material millions of times, it uses a light-based signal that directly changes when cancer biomarkers are present. That makes the process faster, potentially simpler, and less prone to background noise. 

What the researchers found about sub-attomolar detection 

The sensor focuses on microRNAs, which are tiny strands of RNA that regulate gene expression. According to the researchers, certain microRNAs, such as miR-21, miR-155 and miR-10b, are strongly linked to early tumour development, particularly in lung cancer.

 

These molecules circulate in blood long before tumours are visible. The problem is that at early stages, they exist in vanishingly small quantities. Detecting them requires extraordinary sensitivity.

 

In laboratory tests, the device detected miR-21 at concentrations down to 168 zeptomolar (zM). To put that in perspective, a zeptomolar concentration corresponds to roughly a few dozen molecules in a typical test sample.

 

The researchers relied on second harmonic generation (SHG), a nonlinear optical effect. When intense light hits certain materials, it can emit light at exactly half the original wavelength. This emitted signal is extremely sensitive to surface-level molecular changes.

 

The researchers used a single layer of molybdenum disulphide (MoS₂), a two-dimensional semiconductor known for strong SHG responses. On its own, MoS₂ produces a measurable signal. But the team enhanced it significantly. 

How Crispr enables ultra-sensitive cancer biomarker detection 

According to researchers, Crispr-Cas12a delivers high-potency genome editing and acts as a molecular switch.

 

Each DNA scaffold is programmed with Crispr guide RNA designed to recognise a specific cancer biomarker sequence. When the target microRNA is present, Cas12a becomes activated and cuts DNA linkers holding the quantum dots in place.

 

Once the quantum dots detach, the energy transfer between them and MoS₂ stops. The SHG light intensity drops sharply. That drop becomes the measurable diagnostic signal.

 

Because SHG produces very little background noise, even small molecular changes generate a clear optical response. 

Accuracy of the Crispr SHG sensor in patient blood samples 

The researchers tested blood samples from five healthy individuals and 10 lung cancer patients. According to the clinical validation section of the study, the SHG-based sensor showed stronger signal discrimination between healthy and cancer samples than RT-qPCR.

 

SHG signal changes ranged between 11 per cent and 54 per cent in patient samples, compared to relatively modest variations detected via PCR.

 

Equally important, the sensor ignored closely related microRNA sequences and responded only to perfectly matched targets, demonstrating single-base discrimination capability. 

Could this detect cancer before a tumour appears on a CT scan? 

Potentially, yes. MicroRNAs become dysregulated early in tumour development. If circulating biomarkers can be detected before structural abnormalities are visible on imaging, screening could shift from tumour detection to molecular warning systems.

 

The researchers suggest that future versions of this platform could allow routine blood-based screening for high-risk populations. 

Future uses of Crispr optical biosensors beyond lung cancer 

The study authors say that redesigning the Crispr, the same platform could detect: 

• Other cancer-associated biomarkers 
• Viral infections 
• Bacterial pathogens 
• Environmental toxins 
• Neurodegenerative disease markers such as those linked to Alzheimer’s 

Because it avoids chemical amplification, it may also be suited for rapid bedside diagnostics or portable screening devices.