Researchers at MIT’s Koch Institute for Integrative Cancer Research have designed a miniature biochemical sensor, which can be implanted in cancerous tissue during the preliminary biopsy.
Although doctors have several forms of radiation and chemotherapy to battle cancer, which claims almost eight million people annually, they do not have an appropriate and reliable means for gathering real-time data about the effectiveness of a therapy for a specific patient.
Magnetic resonance imaging and other scanning technologies provide data on the size of a tumor. Comprehensive data regarding the effectiveness of treatment, comes from the tests conducted by a pathologist on the tissue taken during biopsy. However, these techniques do not give the full picture, just snapshots of tumor response, and clinicians tend to reduce invasive procedures due to the risk factor.
MIT researchers have now attempted to resolve this lack of precise data. The biochemical sensor created by them can wirelessly transmit data regarding prognostic biomarkers to an external “reader” device. Based on the data received, doctors can monitor the progress of a patient in a better manner and change therapies or alter dosages. By ensuring that cancer treatments are more targeted and accurate, their efficacy can be boosted while decreasing the patients’ exposure to severe side effects.
“We wanted to make a device that would give us a chemical signal about what’s happening in the tumor,” says Michael Cima, the David H. Koch (1962) Professor in Engineering in the Department of Materials Science and Engineering and a Koch Institute investigator who oversaw the sensor’s development. “Rather than waiting months to see if the tumor is shrinking, you could get an early read to see if you’re moving in the right direction.”
Two MIT doctoral students in Cima’s lab worked with him on the sensor project - Vincent Liu, now a postdoc at MIT, and Christophoros Vassiliou, now a postdoc at the University of California at Berkeley. Their research was published online in the journal Lab on a Chip.
Measurements without MRI
The sensor created by Cima’s team is capable of providing instantaneous, on-demand data relating to two biomarkers connected to a tumor’s reaction to treatment - dissolved oxygen and pH.
Cima explains that cancerous tissue tends to become more acidic when attacked by chemotherapy agents. “Many times, you can see the response chemically before you see a tumor actually shrink,” Cima says. Certain therapies can activate an immune system reaction, and the inflammation caused will make the tumor look like it is increasing in size, although the therapy is actually successful.
As tumors flourish in low-oxygen or hypoxic conditions, data regarding oxygen levels will assist doctors in determining the appropriate therapy dosage such as radiation.
“It turns out that the more hypoxic the tumor is, the more radiation you need,” Cima says. “So, these sensors, read over time, could let you see how hypoxia was changing in the tumor, so you could adjust the radiation accordingly.”
The sensor is so small that its housing, which is made of a biocompatible plastic, can fit into the tip of a biopsy needle. It holds 10µl of chemical contrast agents normally used for magnetic resonance imaging (MRI) and an on-board circuit to communicate with the external reader unit.
Cima explains that creating a power source for these sensors was vital. His team were involved in constructing a similar implantable sensor four years ago, which was capable of being read by an MRI scanner.
“MRI scans are expensive and not easy to make part of routine care,” he says. “We wanted to take the next step and put some electronics on the device so we could take these measurements without an MRI.”
The novel sensors depend upon the reader for power. The reader is provided with a metal coil inside. The sensor has a comparatively smaller coil inside. When electric current passes, it magnetizes the coil inside the reader. Then that magnetic field generates a voltage in the coil found inside the sensor when the two coils are in close proximity.
This process is termed as mutual inductance. The reader transmits a series of pulses, and the sensor responds. The reader is linked to a computer which interprets the difference in this return signal, thereby highlighting alterations in the targeted biomarkers.
“With these devices, it’s like taking blood pressure. It’s a simple measurement. You get the readout and move on,” says Ralph Weissleder, a radiologist and director of the Center for Systems Biology lab at Massachusetts General Hospital who is familiar with the research. “Whatever you can do right then and there without any complicated testing, the better it is.”
The innovative sensor has been successfully tested in several lab tests as well as on rodents. Cima believes that though the sensors were implanted in the rodents only for a limited period, they can be used for many years to monitor the wellbeing of patients.
“There are thousands of people alive today, because they have implantable electronics, like pacemakers and defibrillators,” he says. “We’re making these sensors out of materials that are in these kinds of long-term implants, and given that they’re so small, I don’t think there will be a problem.”
These preliminary experiments revealed that the sensors were capable of reliably, swiftly and precisely detecting the concentration of pH and oxygen in tissue. Going forward, the MIT team wants to test the effectiveness of the sensors in measuring variations in pH over a longer period of time.
“I want to push these probes so we can use them to monitor tumor response,” Cima says. “We did a little bit of that in these experiments, but we need to make that really robust.”
Cima hopes that although the key application of these sensors would be in cancer treatment, he would like to partner with researchers in many other fields.
“For example, you could use these to measure dissolved oxygen or pH from a lot of different sites all over a pond or a lake,” Cima says. “I’m excited about using these sensors to bring big data to environmental monitoring.”