‘Hearing’ disease

WEST LAFAYETTE, Ind.—When the extracellular matrix surrounding cells in the human body stiffens, it can indicate that cancer is invading other tissue. Monitoring such changes could give researchers another way to study the progression of disease, but detecting changes to the extracellular matrix is difficult to do without damaging it. Researchers have attempted to stretch, compress or apply chemicals to samples of the extracellular matrix to measure this environment, but these methods are expensive or prone to causing damage.

To address this, Purdue University engineers have built a device that would allow disease specialists to load an extracellular matrix sample onto a platform and detect its stiffness through sound waves. The device is described in a study published in the journal Lab Chip. According to the article, the researchers created “a novel noninvasive on-chip platform for characterization of ECM stiffness in vitro, by monitoring ultrasonic wave attenuation through the targeted material.”

As the authors explain, “The device is composed of a pair of millimeter scale ultrasonic transmitter and receiver transducers with the test medium placed in between them. The transmitter generates an ultrasonic wave that propagates through the material, triggers the piezoelectric receiver and generates a corresponding electrical signal ... The ultrasonic stiffness sensing is also demonstrated to successfully monitor dynamic changes in a simulated in vitro tissue by gradually changing the polymerization density of an agarose gel, as a proof-of-concept towards future use for 3D cell culture and drug screening. In situ long-term ultrasonic signal stability and thermal assessment of the device demonstrates its high robust performance even after two days of continuous operation…In vitro biocompatibility assessment of the device with mammary fibroblasts further assures that the materials used in the platform did not produce a toxic response and cells remained viable under the applied ultrasound signals in the device.”

According to Rahim Rahimi, a Purdue assistant professor of materials engineering whose lab develops innovative materials and biomedical devices to address healthcare challenges, “It’s the same concept as checking for damage in an airplane wing. There’s a sound wave propagating through the material and a receiver on the other side. The way that the wave propagates can indicate if there’s any damage or defect without affecting the material itself. Each tissue and organ has its own unique extracellular matrix, which comes with structural and chemical cues that support communication between individual cells housed in the matrix.”

Rahimi explained that the extracellular environment has great impact on how structures respond. Cancer cells, which have a stiffer extracellular environment, respond differently to chemotherapy. “We create that environment on a chip to study the effects of therapeutics and get responses that are more likely to correspond to what happens inside the human body,” he said.

To develop a nondestructive way to analyze how the extracellular matrix responds to disease, toxic substances or therapeutic drugs, the team performed its initial work in collaboration with the lab of Sophie Lelièvre, a professor of cancer pharmacology at Purdue. The researchers identified the way risk factors affect the extracellular matrix and increase the risk of developing breast cancer and then developed models that mimic the lung and colon environment.

The “lab-on-a-chip” is connected to a transmitter and receiver. After putting the extracellular matrix and the cells it contains onto the platform, the transmitter generates an ultrasonic wave that propagates through the material and then triggers the receiver. The output is an electrical signal indicating the stiffness of the extracellular matrix.

Rahimi and his team initially demonstrated the device as a proof of concept with cancer cells contained in hydrogel, a material with a consistency similar to an extracellular matrix. Currently, the researchers are studying the device’s effectiveness on collagen extracellular matrices. Rahimi noted that the device could easily be scaled up to run many samples at once, such as in an array, enabling researchers to look at several different aspects of a disease simultaneously.

“Our lab-on-a-chip device would minimize the need and use of animal studies,” he remarked. “In addition, the use of human cells provides a better response that is closer to what happens in clinical trials.”

Currently, the researchers are still performing lab studies with the device, but they plan to take the next step of submitting a proposal for a clinical trial. Then they plan to talk to startup companies in a year or two to develop a prototype version for research labs, according to Rahimi.