New Device to capture and Test CSCs

New Device to capture and Test CSCs

Captures Cancer Cells From Blood

By capturing more cancer cells than blood draw screening, this device could help doctors understand a tumor’s biology and make decisions about treatment.

Sunitha Nagrath, Ph.D., associate professor of chemical engineering at U-M, led the development of the device.

A prototype wearable device, tested in animal models, can continuously collect live cancer cells directly from a patient’s blood.

Developed by a team of engineers and doctors at the University of Michigan, it could help doctors diagnose and treat cancer more effectively.

“Nobody wants to have a biopsy. If we could get enough cancer cells from the blood, we could use them to learn about the tumor biology and direct care for the patients. That’s the excitement of why we’re doing this,” says Daniel F. Hayes, M.D., the Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Rogel Cancer Center and senior author on the paper in Nature Communications.

Tumors can release more than 1,000 cancer cells into the bloodstream in a single minute. Current methods of capturing cancer cells from blood rely on samples from the patient—usually no more than a tablespoon taken in a single draw. Some blood draws come back with no cancer cells, even in patients with advanced cancer, and a typical sample contains no more than 10 cancer cells.

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“This is the epitome of precision medicine, which is so exciting in the field of oncology right now.”

Daniel F. Hayes, M.D.

Over a couple of hours in the hospital, the new device could continuously capture cancer cells directly from the vein, screening much larger volumes of a patient’s blood. In animal tests, the cell-grabbing chip in the wearable device trapped 3.5 times as many cancer cells per milliliter of blood compared to the traditional blood draw samples.

“It’s the difference between having a security camera that takes a snapshot of a door every five minutes or takes a video. If an intruder enters between the snapshots, you wouldn’t know about it,” says Sunitha Nagrath, Ph.D., associate professor of chemical engineering at U-M, who led the development of the device. Nagrath is part of the Rogel Cancer Center and the Biointerfaces Institute at U-M.

Research shows that most cancer cells can’t survive in the bloodstream, but those that do are more likely to start a new tumor. Typically, it is these satellite tumors, called metastases, that are deadly, rather than the original tumor. This means cancer cells captured from blood could provide better information for planning treatments than those from a conventional biopsy.

The team tested the device in dogs at the Colorado State University’s Flint Animal Cancer Center in collaboration with Douglas Thamm, V.M.D., a professor of veterinary oncology and director of clinical research there. They injected healthy adult animals with human cancer cells, which are eliminated by the dogs’ immune systems over the course of a few hours with no lasting effects.

For the first two hours post-injection, the dogs were given a mild sedative and connected to the device, which screened between 1-2 percent of their blood. At the same time, the dogs had blood drawn every 20 minutes, and the cancer cells in these samples were collected by a chip of the same design.

The device shrinks a machine that is typically the size of an oven down to something that could be worn on the wrist and connected to a vein in the arm. For help with the design, the engineering team turned to Laura Cooling, M.D., a professor of clinical pathology at U-M and associate director of the blood bank, where she manages the full-size systems.

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The green circuit board inside the device controls the blood pump, heparin injector and display data.

Illustration: Tae Hyun Kim

“The most challenging parts were integrating all of the components into a single device and then ensuring that the blood would not clot, that the cells would not clog up the chip, and that the entire device is completely sterile,” says Tae Hyun Kim, Ph.D., who earned his doctorate in electrical engineering in the Nagrath Lab and is now a postdoctoral scholar at the California Institute of Technology.

They developed protocols for mixing the blood with heparin, a drug that prevents clotting, and sterilization methods that killed bacteria without harming the cell-targeting immune markers, or antibodies, on the chip. Kim also packaged some of the smallest medical-grade pumps in a 3D-printed box with the electronics and the cancer-cell-capturing chip.

The chip itself is a new twist on one of the highest-capture-rate devices from Nagrath’s lab. It uses the nanomaterial graphene oxide to create dense forests of antibody-tipped molecular chains, enabling it to trap more than 80 percent of the cancer cells in whole blood that flows across it. The chip can also be used to grow the captured cancer cells, producing larger samples for further analysis.

In the next steps for the device, the team hopes to increase the blood processing rate. Then, led by Thamm, they will use the optimized system to capture cancer cells from pet dogs that come to the cancer center as patients. Chips targeting proteins on the surfaces of canine breast cancer cells are under development in the Nagrath lab now.

Hayes estimates the device could begin human trials in three to five years. It would be used to help to optimize treatments for human cancers by enabling doctors to see if the cancer cells are making the molecules that serve as targets for many newer cancer drugs.

“This is the epitome of precision medicine, which is so exciting in the field of oncology right now,” Hayes says.

 

MORE ARTICLES ABOUT: Cancer Research, Cancer: Help, Diagnosis & Treatment

https://labblog.uofmhealth.org/health-tech/biopsy-alternative-wearable-device-captures-cancer-cells-from-blood

https://www.nature.com/articles/s41467-019-09439-9

Article | OPEN | Published: 01 April 2019

A temporary indwelling intravascular aphaeretic system for in vivo enrichment of circulating tumor cells

  • Tae Hyun Kim, Yang Wang, C. Ryan Oliver, Douglas H. Thamm, Laura Cooling, Costanza Paoletti, Kaylee J. Smith, Sunitha Nagrath & Daniel F. Hayes

Nature Communications

volume

 10, Article number: 1478 (2019) | Download Citation

Abstract

Circulating tumor cells (CTCs) have become an established biomarker for prognosis in patients with various carcinomas. However, current ex vivo CTC isolation technologies rely on small blood volumes from a single venipuncture limiting the number of captured CTCs. This produces statistical variability and inaccurate reflection of tumor cell heterogeneity. Here, we describe an in vivo indwelling intravascular aphaeretic CTC isolation system to continuously collect CTCs directly from a peripheral vein. The system returns the remaining blood products after CTC enrichment, permitting interrogation of larger blood volumes than classic phlebotomy specimens over a prolonged period of time. The system is validated in canine models showing capability to screen 1–2% of the entire blood over 2 h. Our result shows substantial increase in CTC capture, compared with serial blood draws. This technology could potentially be used to analyze large number of CTCs to facilitate translation of analytical information into future clinical decisions.

Introduction

Cancer metastases arise from circulating tumor cells (CTCs) that are shed from the primary tumor and circulate through lymphatic channels and blood1.

Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646–674 (2011).

Although identified more than 150 years ago2, until recently, CTCs were difficult to detect, enumerate, and characterize.

Ashworth, T. R. A case of cancer in which cells similar to those in the tumours were seen in the blood after death. Australas. Med. J. 14, 146–149 (1869).

 

 

Alternative: ‘Wearable’ Device Captures Cancer Cells From Blood

By capturing more cancer cells than blood draw screening, this device could help doctors understand a tumor’s biology and make decisions about treatment.

 

Sunitha Nagrath, Ph.D., associate professor of chemical engineering at U-M, led the development of the device.

A prototype wearable device, tested in animal models, can continuously collect live cancer cells directly from a patient’s blood.

Developed by a team of engineers and doctors at the University of Michigan, it could help doctors diagnose and treat cancer more effectively.

“Nobody wants to have a biopsy. If we could get enough cancer cells from the blood, we could use them to learn about the tumor biology and direct care for the patients. That’s the excitement of why we’re doing this,” says Daniel F. Hayes, M.D., the Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Rogel Cancer Centerand senior author on the paper in Nature Communications.

Tumors can release more than 1,000 cancer cells into the bloodstream in a single minute. Current methods of capturing cancer cells from blood rely on samples from the patient—usually no more than a tablespoon taken in a single draw. Some blood draws come back with no cancer cells, even in patients with advanced cancer, and a typical sample contains no more than 10 cancer cells.

 

 

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