Researchers from the University of Michigan have developed a novel approach for diagnosing lung cancer using a blood test that is 10 times quicker and 14 times more sensitive than previous techniques.
Researchers from the University of Michigan have introduced a faster and more sensitive blood test for lung cancer diagnosis, being 10 times quicker and 14 times more accurate than older methods.
The University of Michigan has created a microchip that collects exosomes—tiny carriers released by cells—from blood plasma to detect lung cancer indicators.
Initially thought to be waste products, exosomes have been revealed over the last decade to be crucial for cell communication, containing proteins and DNA or RNA fragments. While healthy cell exosomes transmit essential signals in the body, those from cancer cells can facilitate tumor growth by preparing the surrounding tissues for the incoming tumor cells.
“Exosomes released from tumors help to prepare the surrounding environment, allowing cancer cells to reach and grow in these more favorable conditions,” explained Sunitha Nagrath, a U-M professor of chemical and biomedical engineering and co-author of the research published in the journal Matter.
Exosomes contain proteins both internally and on their surface. These surface proteins are chiral, meaning they twist either to the right or left, resulting in unique interactions with light.
In cancerous exosomes, these surface proteins often have mutations that alter the arrangement of the molecules they comprise, subtly altering the protein’s shape and chirality.
These distinctions can be detected through their reaction to twisted, or circularly polarized, light, which matches the protein’s twist. This reaction generates a strong signal that can be detected. However, the light signals are generally weak and challenging to analyze. Moreover, isolating exosomes from blood samples is complicated due to their minuscule size, typically ranging from 30 to 200 nanometers (one millionth of a millimeter).
To effectively capture these exosomes, the research team designed gold nanoparticles shaped like twisted disks (based on a design first introduced in a 2022 Nature study) that enclose exosomes within a central cavity. Thanks to a nearly perfect match in their size, shape, and surface properties, these cavities effectively trap exosomes.
Exosomes with a right-handed twist resonate strongly with right-twisting light, while yielding minimal signals for left-handed light. This distinctive response is known as circular dichroism. The exosome’s surface proteins, embedded in the cavity, can either amplify or dampen the return signal depending on their shapes. Positioned along the tiny channels of a microfluidic chip, these gold cavities captured exosomes from blood plasma and revealed clear differences between samples from healthy participants and those diagnosed with lung cancer.
“While I anticipated that the optical properties of nanoparticles would correlate with the mutations in the proteins, I was surprised at their sensitivity. This is largely attributed to the uniform orientation of nanoparticles within the detection device,” remarked Nicholas Kotov, the Irving Langmuir Distinguished University Professor of Chemical Sciences and Engineering at U-M and co-author of the study.
The microfluidic chips, referred to as CDEXO chips for Circular Dichroism detection of EXOsomes, have the potential to differentiate between specific mutations in lung cancer, enabling physicians to make treatment decisions that target the primary mutations as they evolve.
The researchers hope to initially use the CDEXO chip alongside traditional diagnostic methods. As its reliability is demonstrated, the chip may be employed to screen for other types of cancer, enhancing early detection rates.
“Our next step involves examining the spectral signatures of most known solid tumor mutated proteins to better understand their differences. This will allow us to enhance technological capabilities to further distinguish between these proteins,” Nagrath stated.
Kotov also holds the Joseph B. and Florence V. Cejka Professorship in Engineering and is a professor of macromolecular science and engineering. Nagrath co-directs the Liquid Biopsy Shared Resources at the University of Michigan Rogel Cancer Center.
This research was conducted at the Lurie Nanofabrication Facility and the Michigan Center for Materials Characterization, with contributions from the Rogel Cancer Center providing cell lines and clinical expertise.
