Stanford University engineers are developing a wearable device that could measure tumor regression accurately and noninvasively following drug therapy initiation, according to a study published on Friday in Science Advances.
The device may provide an inexpensive and hands-free way to evaluate the efficacy of cancer drugs and could lead to promising new directions in cancer treatment, its developers said.
The group developed a proof-of-concept elastomeric-electronic tumor volume sensor, called Flexible Autonomous Sensor measuring Tumors, or Fast, for use in mouse models to test the efficacy of cancer drugs in preclinical trials. The wearable device measures the changing size of tumors below the skin.
Battery-powered and attachable to the skin, Fast can read out cancer treatment efficacy studies in vivo and send results wirelessly to a smartphone app, the authors of the Science Advances study said.
The team used its technology to scan 27 tumors, taking measurements every five minutes. In two in vivo cancer mouse models, the sensor discerned "differences in tumor volume dynamics between drug- and vehicle-related tumors" within five hours of therapy initiation. Short-term regression was validated through histology. Caliper and bioluminescence measurements taken over the course of a week showed correlation with longer-term treatment response.
The engineers noted that the technology can measure volume changes in ellipsoids as small or as large as 65 and 750 mm3, respectively, demonstrating its high-resolution capabilities.
A wearable device that could measure tumor regression accurately and noninvasively following drug therapy initiation would be important for numerous reasons.
Thousands of therapeutic drugs are tested on mice, but few make it to human patients. Verification takes time. Along with this inefficiency, "inherent biological variations combined with low-resolution measurement tools and small sample sizes make determining drug efficacy in vivo a difficult, labor-intensive task," the study authors wrote.
Other methods of tumor regression measurement come with their own limitations, too. Toxicity concerns and high cost restrict the application of computed tomography (CT) and bioluminescence imaging. Other types of sensors, such as implantable pressure sensors, are invasive and work best in tumors encapsulated by a solid environment, such as bone. Calipers may be used to measure small samples, but the authors noted that the precision of calipers is affected by the pressure a user applies to them.
In contrast, the Stanford team's sensor circumvents these issues by automating in vivo testing through continuous, autonomous monitoring "of subcutaneously implanted tumors at the minute time scale," the authors said. Fast can remain in place over the measurement period, taking measurements regularly, and generate a four-dimensional, time-dependent dataset, eliminating guesswork on measurement timing.
These findings led the researchers to consider expanding the sensor's use. Along with improving the time it takes to verify a therapeutic drug, the technology may assist in determining differences between normal progression and pseudo-progression growth rates. The authors raised the idea that the sensor could be combined with drug delivery systems to enable a theranostic closed-loop delivery platform, although this would require future studies.
The authors further suggested that the sensor could be manufactured easily and in mass quantity, writing, "Each reusable sensor backpack costs ~$60, can be scaled for mass manufacturing, and takes <5 min of low-skill work to apply to an animal." The sensor is fabricated by depositing a 50-nm layer of gold on top of a drop-casted layer of styrene-ethylene-butylenestyrene.
Fast does have limitations, however. The size limitations of the mouse models, along with the volume of the printed circuit board (PCB) and battery, prevented its implantation. For this reason, the implantable version of this sensor was not tested in vivo during the experiments, and the experiments were limited to testing on subcutaneous tumors.
The sensor's battery life was also limited; the device could not run for 24 hours. "Further work optimizing the battery life and size of the associated electronic PCB is required in pursuit of a longer-lasting and implantable sensor system," the authors wrote.
