SEEING THE INVISIBLE WITH MICROFLUIDIC DEVICES
Microfluidics is all about controlling the flow of liquids on the micro-scale. Much like an engineer might build a series of dams and channels to steer the course of a river, in microfluidics tiny channels are etched onto circuit boards, smaller than a human fingernail, through which miniscule volumes of chemicals and other liquids can flow. One use of this technology is for everyday inkjet printers, where the channels help carefully control where the ink is sprayed in the printing process.
These channels can also be merged, allowing two separate chemicals to mix and react, which is why some of these microfluidic devices are sometimes known as the ‘lab-on-a-chip’.
This team of investigators is led by Dr. Christopher T. Culbertson and Dr. Stefan H. Bossmann at Kansas State University. We are very excited by some of the possibilities that microfluidics and the lab-on-a-chip offer. In our highly interdisciplinary and collaborative project, our teams are working together to develop this technology into a miniature analysis lab. Our technology will, for the first time, offer profiling sufficiently rapid that it could be used to monitor a patient’s response to disease treatments.
Such a device would also have the unprecedented ability to perform other kinds of cell analysis, in combination with the team’s work to design and synthesize new markers to help report cell activities, such as proteolytic profiles for early cancer detection.
Microfluidic devices are inherently well-suited to looking at biological processes, as the micrometer channel size conveniently corresponds to the size of cells. Most cells are between 1 – 100 micrometers, with a human hair being approximately 60 micrometers thick. This means that the channels can not only be used to provide a highly controlled
environment for cell growth, that is often more effective than a human-scale lab, but also to separate out different cells of different sizes.
We have already succeeded at using optical fibers to integrate this light detection technology onto their lab-on-a-chip. What is unique about our design and project is off-chip placement of the optical fiber bridge: this means the chip design is not further complicated by the inclusion of the fiber. One of the big challenges with microfluidic devices is in their manufacture; making components on such small scales is difficult to do reliably and inexpensively so this is a key advantage of our design.
Another unique feature of our project is creating a microfluidic device with multiple detection and excitation spots to detect the sample of interest, while still using only one laser and detector. The motivation behind this is to increase the versatility and capabilities of the device. Now with the integration of the optical fibers they can detect the intact cell before breakdown of the cell membrane as well as the components from the cell after it is lysed. Each of the excitation spots on the microchip is like a viewing
window for the cell’s activities, so the greater the number of spots you have, the greater the amount of information you can obtain. And with more information, it becomes possible to better understand exactly how diseases lead to deformation and destruction of the cell.
We want to go beyond just being able to image and identify cells. As part of this joint project, we are working on the development of new biomarkers for single-cell detection. This work involves designing very bright markers, so when the cells bind a chemical marker that glows after it absorbs light from a laser, this emitted light from the cell is sufficiently intense that a single molecule in a single cell can be detected. These markers also have to be rapidly taken up by the cell so that the detection can be done in ‘real time’. This is important if this device will be used to reduce patient diagnosis times.
By making it easier to see the cells, and developing highly selective markers, our teams made it possible to investigate enzymatic activity and how cytokines, small proteins that are commonly produced by cells in association with disease, behave. The more sophisticated protease detection (detection of the enzymes that break down proteins) offered by their lab-on-a-chip will make it possible to understand how the misregulation of enzyme activity leads to the development of various diseases.
The large number of enzyme markers that can be monitored will allow for the detection of many possible diseases. The work combining optical fibers with microfluidic devices will open up many new possibilities in understanding diseases at the cellular level and more tools for cell imaging and diagnosis. All of this is an important part in the development of lab on-a-chip technology for making rapid, handheld diagnostic devices a routine part of healthcare.
Dr. Madumali Kalubowilage (Postdoctoral Scientist)
Kansas State University
Department of Chemistry
213 CBC Building
Manhattan, KS 66506
Dr. Jalal Sadeghi (Postdoctoral Scientist)
Department of Chemistry
311 King Hall
Manhattan, KS 66506
Jay Sibbitts, Obdulia Covarrubias-Zambrano, Shu Jia, Jose Covarrubias, Abigail Kreznor, Sumia Ehsan