Implantable gene mutation real-time detection device helps cancer precise treatment

Professor RatneshLal said: “Now there are wearable devices that monitor heart rate, exercise status and blood sugar levels. If the human gene mutation status can be continuously monitored in real time, then how good would it be. With my limited IQ, I can think of Applications include early screening for cancer and post-treatment monitoring. If this is true, patients can always be in control of their health. That's wonderful."

Unexpectedly, this scientific concept was implemented by the Ratnesh Lal team of the University of California, San Diego. Scientists once again gave me a lesson with their research papers: “The dream still needs to happen. If it is realized!” On June 13, the research results of the Lal team were published in the Proceedings of the National Academy of Sciences.

In fact, Lal developed this device to detect human-specific gene mutation sites (SNPs) as well as 23andMe. Although the role of scientists for most of the SNPs is not yet clear, scientists have also found special SNPs associated with cancer, diabetes, heart disease, neurological diseases, autoimmune and inflammatory diseases. Professor Lal is developing an implantable chip that can detect disease-related SNPs in real time.

The structure of this chip is also very simple, that is, the probes that can find special SNPs are fixed on the graphene field-effect transistors (FETs). Once specific SNPs related to the disease appear, the probes will capture them. The electrical signal was generated at this instant. Then the chip will send a signal to the phone to alert the user of gene-related mutations in the body. At this time, we should put aside our hands and go to the hospital for further inspections.

Only in principle, this device does not seem to differ much from the traditional DNA chip except that it will have the ability to monitor and send signals in real time. In fact, this device is far from simple. Its kung fu is now in full detail. In detail, it has three major advantages that SNPs testing equipment does not have.

First of all, unlike the single-stranded probes of traditional DNA chips, this chip developed by Professor Lal is a double-stranded probe, but there is only a single strand at the junction of the probe and the chip. Those people will ask, how does this double-stranded probe capture free DNA? Professor Lal modified this special probe. The chain attached to the graphene field effect transistor is a normal chain and can capture DNA fragments carrying special SNPs. The other probe on the probe is shorter and has been modified. Binding to the normal chain is relatively loose. When the DNA fragment carrying the special SNP is bound to the probe from below, the short chain will fall off automatically. According to Professor Lal, this design can greatly avoid probes catching wrong objects and greatly improve the accuracy of detection.

The 47 nt double-stranded probe has a 7 nt single strand near the graphene field-effect transistor. Followed by the process of binding the probe to the target gene fragment

Second, the design of the probes connected to the graphene field effect transistors captures the DNA fragments carrying special SNPs and successfully converts them into electrical signals. This is the first time that DNA dynamics and high resolution electrical signals have been combined for the first time in history. It is this combination that creates miracles and makes it possible to use mobile phones to monitor specific gene mutations in the body.

Finally, double-stranded probes have a huge advantage. It is possible to design the probe long. It's known to all creatures that the longer the probe, the more accurate the result of the test. Some time ago, the NgAgo gene editing technology discovered by teacher Han Chunyu was because the guiding part was a bit longer than CRISPR, and the accuracy was improved thousands of times at once. Because Professor Lal uses a double-stranded probe, the probe itself does not bind, so that the length of the probe can be greatly extended. According to Professor Lal's paper, they used a 47-base probe, which is the longest probe in the history of detecting SNPs. Needless to say, the accuracy of this chip has greatly improved.

Targeted DNA fragment before binding (left), target DNA fragment after binding (right)

According to Preston Landon, co-first author of this research paper, the current detection of SNPs requires complex equipment, and the process is relatively slow and costly. The chip they developed is relatively simple, fast, and inexpensive, and even more powerful is that it can be used with mobile phones to monitor the specific gene mutations in the body in real time.

According to Professor Lal, their research is still in its early stages, but they have already monitored the genetic mutations in real time and sent the mutation status to mobile phones. Next they will further optimize the technology and add wireless connectivity and transmission capabilities to the chip. The time is ripe, they will bring the chip into the clinic and carry out liquid biopsy tests. Professor Lal believes that their technology will lead a new generation of detection and precise treatment methods.

From the technical principle of this device, this invention is indeed exciting enough. Especially in the early detection of cancer and post-treatment monitoring, it can give us unlimited imagination. And once this technology is mature, it will also promote basic research related to cancer, especially in the evolution of tumors. But from the current point of view, it also has some flaws. The main thing should be that there are fewer sites that can be monitored at the same time. Another big problem is that basic research has not been able to keep up. There is no way to directly prove that genetic mutations can predict the risk of disease. This is why 23andMe and the FDA are flustered.

On June 1, the FDA approved the Roche gene mutation detection technology for NSCLC, which is the first FDA approved liquid biopsy product. This means that Roche became the first company to use liquid biopsy to diagnose cancer. In addition, on June 4th, the California-based startup GuardantHealth released exciting research data at the just-concluded 2016 annual meeting of the American Society of Clinical Oncology, demonstrating that liquid biopsy has the strength to replace tissue biopsy.

All these indicate that the relationship between gene mutation and cancer is gradually established. We have reason to believe that real-time detection of implantable genetic mutations will sooner or later into our lives.

(Original title: Heavy! New detection equipment will enable genetic testing into the era of implantation)