The idea of growing tissue in the lab to help humans restore lost organs or limbs has generated research on a number of fronts. For their part, scientists at the National Institute of Standards and Technology (NIST) are developing a new kind of light-based sensor to study tissue growth in the lab.
The NIST team’s proof-of-concept, published in Sensors and Actuators B, demonstrates a small sensor that uses a light-based signal to measure pH, the measurement unit for acidity, an important property in cell-growth studies. The same basic design could be used to measure other qualities such as the presence of calcium, cell growth factor and certain antibodies.
This measurement technique could be used to monitor the environment in a cell culture long-term—for weeks at a time—without having to disturb the cells regularly to calibrate the sensing instruments. The ability to monitor the tissue’s properties in real time for days or weeks could benefit tissue engineering studies to grow teeth, heart tissue, bone tissue and more, according to NIST chemist Zeeshan Ahmed.
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“We want to make sensors that can be put inside growing tissue to give researchers quantitative information,” Ahmed said in an article on NIST’s website. “Is the tissue actually growing? Is it healthy? If you grow a bone, does it have the right mechanical properties or is it too weak to support a body?”
The research could also help scientists understand the effects of disease progression on tissue growth.
“What these sensors could give people is real-time information about tissue growth and disease progression,” said American University chemist and NIST guest researcher Matthew Hartings. Conventional sensors give researchers a series of snapshots without showing them the path between those points, Hartings said. But photonic sensors could provide scientists with continuous information, the equivalent of a GPS navigation app for disease.
Measurements of pH are a vital part of tissue engineering studies. As cells grow, their environment naturally becomes more acidic. If the environment becomes too acidic—or too basic—the cells will die. Scientists measure pH on a scale from 0 (very acidic) to 14 (very basic), with an ideal environment for most cells in a narrow range around a pH of 7.
Commercial pH instruments are unstable, meaning they require frequent calibrations to ensure accurate readings day to day. Without calibration, these conventional pH meters lose up to 0.1 pH units of accuracy daily. But tissue engineering studies take place on the order of weeks. A culture of stem cells might need to be grown for almost a month before they turn into bone.
“An increment of 0.1 pH is significant,” Ahmed said. “If your pH value changes by 1, you kill the cells. If after a few days I can’t trust anything about my pH measurement, then I’m not going to use that measurement method.”
Ahmed added that a measurement system is needed that can stay inside an incubator with the cells in their culture medium and not need to be removed or calibrated for weeks at a time.
For years, Ahmed and his team have been developing photonic sensors, small lightweight devices that use optical signals to measure a range of qualities including temperature, pressure and humidity.
To adapt their photonic devices to a pH measurement, Ahmed and Hartings relied on a well-known concept in science: When an object absorbs light, the energy absorbed “has to go somewhere,” Ahmed said, and in many cases that energy turns into heat.
For their demonstration, the scientists used a substance that changes color in response to changes in pH: red cabbage juice powder. Cabbage juice changes its color from shades of dark purple to light pink, depending on the acidity of a solution. That change in color can be picked up by Ahmed’s photonic temperature sensors.
Researchers filled a petri dish with the cabbage juice solution. One optical fiber was positioned above the dish. It was connected to a laser pointer and shined light into the sample. A second optical fiber was physically embedded in the liquid. This second fiber contained the Bragg grating and acted as the temperature sensor. Ahmed’s team controlled the solution’s pH manually.
To make a measurement, the researchers shone one color of light—such as red—into the sample from above. The cabbage juice absorbed the red light to varying degrees based on its color, which depended on the pH of the solution at that time. The photonic thermometer fiber picked up these slight changes in the juice’s heat. A change in temperature changes the wavelengths of light that can pass through the fiber’s Bragg grating.
Next, the researchers shone a second color of light into the liquid, and repeated the process.
By comparing how much heat was generated by each color of light, researchers could determine the exact color of the cabbage juice at that moment, and that told them the pH.
Ongoing work shows the photonic pH measurements are accurate to plus or minus 0.13 pH units and are stable for at least three weeks, much longer than conventional measurements.