New microchip captures exosomes for faster, more sensitive detection of lung cancer from a blood test

A new way to diagnose lung cancer with a blood test is 10 times faster and 14 times more sensitive than previous methods, according to University of Michigan researchers.

The microchip developed at UM captures exosomes – tiny packets released by cells – from blood plasma to identify signs of lung cancer.

Once thought of as waste ejected from cells for cleaning, researchers have discovered over the past decade that exosomes are tiny parcels containing proteins or fragments of DNA and RNA valuable for communication between cells. Although exosomes from healthy cells transmit important signals throughout the body, exosomes from cancer cells can help tumors spread by preparing tissues to accept tumor cells before they arrive.

“The cancer exosomes leaving the tumor microenvironment come out and sort of prepare the soil. Later, the seeds of the cancer cells are shed by the tumor and travel through the bloodstream to plant themselves in the conditioned soil and begin to grow,” said UM professor Sunitha Nagrath. of chemical and biomedical engineering and co-corresponding author of the study in the journal Matter.

Exosomes carry proteins both within the parcel and on their outer surface. Like many biological molecules, these surface proteins are chiral, meaning they have a right- or left-hand twist, which causes them to interact with light in unique ways.

In cancer exosomes, the surface proteins are often mutated, meaning that a genetic change has altered the order of the molecules that make up the protein. Mutations subtly change the shape of the protein, which also changes its chirality.

These differences can be spotted through interactions with twisted or circularly polarized light, which can correspond to the twist of the protein. The resonance creates a strong signal sent back to a light detector. However, these light signatures are generally faint and difficult to interpret. Additionally, exosomes must be extracted from a blood sample to perform this type of detection. This is tricky because exosomes are small, measuring just 30 to 200 nanometers (one millionth of a millimeter).

To spot them, the research team designed gold nanoparticles shaped like twisted disks (adapted from a structure first described in a 2022 study). Nature study) which capture exosomes in a central cavity. Due to a near-perfect match in size, shape, and surface chemistry, these cavities capture exosomes reliably.

With a right-hand twist, they resonate strongly with light spinning to the right, but don’t return much signal if the incoming light has a left-hand twist. This different response to twisted light is known as circular dichroism.

The proteins of the captured exosomes, inserted into the cavity, can strengthen or reduce the intensity of the return signal depending on their shape. Studded along the tiny channels of a microfluidic chip, the gold cavities captured exosomes from blood plasma and revealed distinct signatures between samples given by healthy study participants and those with breast cancer. lung.

“While I expected the optical activity of the nanoparticles to depend on protein mutations, I was pleasantly surprised by its sensitivity. This is because the nanoparticles are all oriented the same way in the device detection.” said Nicholas Kotov, Irving Langmuir Distinguished Professor of Chemical Sciences and Engineering at UM and co-corresponding author of the study.

Microfluidic chips, called CDEXO chips for circular dichroism detection of EXOsomes, may be able to distinguish specific lung cancer mutations, helping doctors make treatment decisions to target dominant mutations as they evolve .

The researchers envision that the CDEXO chip will first be used alongside traditional diagnostic methods. As confidence in the technology grows, the chip could be used to screen for other cancers to improve early detection.

“As a next step, we want to look at mutated proteins from the best-known solid tumors to understand how their spectral signatures are different. From there, we can push the technology to further increase these spectral differences to distinguish proteins.” , Nagrath said.