03 April 2019

Biochip for "liquid biopsy"

Wearable devices with a chip can become an alternative to biopsy

Lina Medvedeva, XX2 century

The wearable device, a 2x2.75x1 inch prototype tested on animal models, can continuously collect live cancer cells directly from the patient's blood.

The device was developed by a group of engineers and doctors at the University of Michigan and can help doctors diagnose and treat cancer more effectively.

"No one wants to do a biopsy. If we could get enough cancer cells from the blood, we could use them to study the biology of the tumor and directly treat patients. Our experiment is aimed at just that," says Daniel F. Daniel F. Hayes, professor at the University of Michigan.

Tumors can emit more than 1,000 cells per minute into the blood. Modern methods of extracting cancer cells from the blood are based on taking samples from the patient. But they are limited by the volume that can be taken at one time – about a tablespoon. Some tests do not show the presence of cancer cells even in patients with advanced cancer, a typical blood sample contains no more than 10 cancer cells.

During a few hours of hospital stay, the new device can continuously capture cancer cells directly from the venous blood, scanning large volumes of the patient's blood. When tested on animals, a chip from a wearable device that captures cells retained 3.5 times more cancer cells per milliliter of blood than was found in samples collected during blood sampling.

"It can be compared to a surveillance camera that takes a photo of the door every five minutes or takes a video. If an attacker passes in between the shots, you won't know about it," says Sunitha Nagrath, who led the development of the device.

Studies show that most cancer cells do not survive in the bloodstream, but those that remain are more likely to contribute to the formation of a new tumor. Usually tumors are satellites, metastases, and are fatal, unlike the original tumor. This means that cancer cells caught from the blood can provide more accurate information for treatment planning than a conventional biopsy.

The researchers tested the device on dogs. Healthy animals were injected with human cancer cells, destroyed by the immune system of dogs for several hours, without having a long-term effect on the body. During the first two hours after the injection, the dogs were given a mild sedative and connected to a device that checks 1 to 2 percent of their blood. At the same time, blood was taken from dogs every 20 minutes, and in these samples, cancer cells were collected using chips of the same design as in the device.

The wearable device makes a conventional oven-sized installation unnecessary, it can be worn on the wrist attached to the veins on the arm. Laura Cooling, a professor of clinical pathology at the University of Michigan, where she works with full-size blood sampling systems, helped design the device.

"The most difficult task is to integrate all the parts into one device and ensure that blood does not clot, cells do not clog the chip, and that the device is completely sterile," says Tae Hyun Kim from the California Institute of Technology (California Institute of Technology).

Special protocols have been developed for mixing blood with heparin, a drug that prevents blood clotting, as well as sterilization methods that kill bacteria without damaging the immune markers of cells in the chip. The scientists also put the smallest medical pumps in a 3D-printed box with electronics and a chip that captures cancer cells.

Biopsy_alternative.jpg

The blood pump is located in the upper left corner of the device, and the heparin injector is located along its entire length. Green boards control the blood pump, the heparin injector and provide data display on the display.

The chip itself is a new development specifically for one of the fastest devices in the laboratory. It uses graphene oxide nanomaterial to create a barrier of molecular chains with antibodies, it allows you to capture more than 80% of cancer cells in whole blood passing through it. The chip can also be used to grow trapped cancer cells, which will allow larger samples to be obtained for further analysis.

In the next stages of the device's development, the researchers hope to increase the speed of blood processing. Subsequently, they will use an optimized system to capture cancer cells in domestic dogs that arrive at the cancer center as patients. The chips are aimed at recognizing breast cancer in dogs.

Hayes believes that human testing of the device may begin in 3-5 years. It will be used to optimize cancer treatment in humans, allowing doctors to observe whether cancer cells produce molecules that are targeted by a variety of new cancer drugs.

Article by Kim et al. A temporary indwelling intravascular aphaeretic system for in vivo enrichment of circulating tumor cells is published in the journal Nature Communications.

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