Lab on a Chip | Atmel | Bits & Pieces

Arduino’s acceptance into the biotech research community is evident from its increasing mentions in high-profile science and engineering journals. Mentions of Arduino in these journals alone have gone from zero to more than 150 in just in the last two years.

While it may be best known as staple for hobbyists, Makers, and hackers who build on their own time, Arduino and Atmel have a strong and rapidly growing following among professional engineers and researchers.

For biotech researchers like myself, experimental setups often require highly specific instruments with strict design rules for parameters such as timing, temperature, motion, force/pressure, and light. Such specific instruments would be time-consuming and expensive to have custom built, as the desired experimental conditions often change as we investigate different samples, cell types, etc. Here, Atmel chips and Arduino boards find a nice niche for making your own affordable, custom setups that are repeatable, precise, and automated. Arduino and Atmel provide microcontrollers in a myriad of form factors, I/O options, and connectivity that are available from a number of vendors. Meanwhile, freeware Arduino code and hardware drivers are also available with many sensors and actuators to go with your board. Best of all, Arduino is designed for a wide audience and range of experiences, making it easy to use for a variety of projects and complexities. So as experimental conditions or goals change, your hardware can easily be re-purposed and re-programmed according to specifications.

Arduino’s acceptance into the biotech research community is evident from its increasing mentions in high profile journals in science and engineering including Nature Methods, Proceedings of the National Academy of the Sciences, Lab on a Chip, Cell, Analytical Chemistry, and the Public Library of Science (PLOS). Mentions of Arduino in these journals alone have gone from zero to more than 150 in just in the last two years.

In recent years, Arduino-powered methods have started to appear in a variety of cutting edge biotechnology applications. One prominent example is optogenetics, a field in which engineered sequences of genes can be turned on and off using light. Using Arduino-based electronic control over lights and motors, researchers have constructed tools to measure how the presence or absence of these gene sequences can produce different behaviors in human neurons [1][6][7] or in bacterial cells [2]. Light and motor control has also allowed for rapid sorting of cells and gene sequences marked with fluorescent dyes, which can be detected by measuring light emitted to photodiodes. While the biology driving this research is richly complex and unexplored, the engineering behind the tools required to observe and measure these phenomena are now simple to use and well-characterized.

Neuroscientists Voights, Sanders, and Newman at the Open Ephys project provide walkthroughs and add-ons for using Arduino to help them create tools for probing cells. From left to right, Arduino-based hardware for creating custom electrodes, providing multi-channel input to neurons, and for control over optogenetic lighting circuits. [6],[7]

Arduino-based automation can be used for supplanting a number of traditional laboratory techniques including control of temperature, humidity, and/or pressure during cell culture conditions; monitoring cell culturing through automated sampling and optical density measurements over time; neurons sending and receiving electrochemical signals; light control and filtration in fluorescence measurements; or measurement of solution salinity. This kind of consistent, automated handling of cells is a key part of producing reliable results for research in cell engineering and synthetic biology.

Synthetic biologists Sauls et al. provide open-source schematics for creating an Arduino-powered turbidostat to automate the culturing of cells with recombinant genes. [5]

Arduino has also found an excellent fit in the microfluidics community. Microfluidics is the miniaturization of fluid-handling technologies—comparable to the miniaturization of electronic components. The development of microfluidic technologies has enabled a myriad of technical innovations including DNA screening microchips, inkjet printers, and the screening and testing of biological samples into compact and affordable formats (often called “lab on a chip” diagnostics) [3]. Their use often requires precise regulation of valves, motors, pressure regulation, timing, and optics, all of which can be achieved using Arduino. Additionally, the compact footprint of the controller allows it to be easily integrated into prototypes for use in medical laboratories or at the point of care. Recent work by the Collins and Yin research groups at MIT has produced prototypes for rapid, point-of-care Ebola detection using paper microfluidics and an Arduino-powered detection system [4].

Microfluidic devices made from paper (left) or using polymers (right) have been used with Arduino to create powerful, compact medical diagnostics (Left: Ebola diagnostic from Pardee et. Al [4], Right: Platelet function diagnostic from Li et al. [9])

Finally, another persistent issue in running biological experiments is continued monitoring and control over conditions, such as long-term time-lapse experiments or cell culture. But what happens when things go wrong? Often this can require researchers to stay near the lab to check in on their experiments. However, researchers now have access to on-board wi-fi control boards [8] that can send notifications via email or text when their experiments are completed or need special attention. This means fewer interruptions, better instruments, and less time spent worrying about your setup.

The compact Arduino Yun microcontroller combines the easy IDE of Arduino with the accessibility of built-in wi-fi to help you take care of your experiments remotely [8]

True to Arduino’s open-source roots, the building, use, and troubleshooting of the Arduino-based tools themselves are also available in active freeware communities online [5]–[7].

Simply put, Arduino is a tool whose ease of use, myriad applications, and open-source learning tools have provided it with a wide and growing user base in the biotech community.

Melissa Li is a postdoctoral researcher in Bioengineering who has worked on biotechnology projects at UC Berkeley, the Scripps Research Institute, the Massachusetts Institute of Technology, Georgia Institute of Technology, and the University of Washington. She’s used Arduino routinely in customized applications in optical, flow, and motion regulation, including a prototype microfluidic blood screening diagnostic for measuring the protective effects of anti-thrombosis medications [9], [10]. The opinions expressed in this article are solely her own and do not reflect those of her institutions of research.

[1] L. J. Bugaj, A. T. Choksi, C. K. Mesuda, R. S. Kane, and D. V. Schaffer, “Optogenetic protein clustering and signaling activation in mammalian cells,” Nat. Methods, vol. 10, no. 3, pp. 249–252, Mar. 2013.

[2] E. J. Olson, L. A. Hartsough, B. P. Landry, R. Shroff, and J. J. Tabor, “Characterizing bacterial gene circuit dynamics with optically programmed gene expression signals,” Nat. Methods, vol. 11, no. 4, pp. 449–455, Apr. 2014.

[3] E. K. Sackmann, A. L. Fulton, and D. J. Beebe, “The present and future role of microfluidics in biomedical research,” Nature, vol. 507, no. 7491, pp. 181–189, Mar. 2014.

[4] K. Pardee, A. A. Green, T. Ferrante, D. E. Cameron, A. DaleyKeyser, P. Yin, and J. J. Collins, “Paper-Based Synthetic Gene Networks,” Cell.

[5] “Evolvinator – OpenWetWare.” [Online]. Available: http://openwetware.org/wiki/Evolvinator. [Accessed: 12-Jan-2015].

[6] “Open Ephys,” Open Ephys. [Online]. Available: http://www.open-ephys.org/. [Accessed: 12-Jan-2015].

[7] Boyden, E. “Very simple off-the-shelf systems for in-vivo optogenetics”. http://syntheticneurobiology.org/protocols/protocoldetail/35/9 [Accessed: 12-Jan-2015].

[8] “Arduino Yun”. http://arduino.cc/en/Guide/ArduinoYun [Accessed: 12-Jan-2015].

[9] “Can aspirin prevent heart attacks? This device may know the answer,” CNET. [Online]. Available: http://www.cnet.com/news/can-aspirin-prevent-heart-attacks-this-device-may-know-the-answer/. [Accessed: 12-Jan-2015].

[10] M. Li, N. A. Hotaling, D. N. Ku, and C. R. Forest, “Microfluidic thrombosis under multiple shear rates and antiplatelet therapy doses.,” PloS One, vol. 9, no. 1, 2014.

(Continued from Part 1 …)

TV: Tell me about the Lab on a Chip?

ML: The lab-on-a-chip (LOC) is a device that integrates one or several laboratory functions on a single chip of only millimeters to a few square centimeters in size. LOCs deal with the handling of extremely small fluid volumes down to less than pico liters. The notion of the “Lab-on-a-Chip” generally indicates the scaling of single or multiple lab processes down to chip-format, primarily dedicated to the integration of the total sequence of lab processes to perform chemical analysis. My previous work examined the design and validation of a LOC for screening blood samples to determine optimal personalized drugs and their respective dosages for specific patients to prevent heart attacks. A lot of those techniques were first inspired by the fact that tools requiring the examination, characterization and integration of the sophisticated hardware controls are made available.

TV: Describe your post doctorate work and bio medical engineering?

ML: I worked on research projects that are helping us to better understand and detect early heart disease. My current research work involves measurements for fluid migration over surfaces then discussing those applications for medical diagnostics. My works also involve motor control for fluorescence microscopy for applications in life sciences. This work involves spectrum study of fluorescent DNA or proteins. This graduate work is related to the building and diagnostic device which can measure at microscale, pinpoint dosage of drugs to show visibility of early signs of heart disease. The medical application revolves around a low cost infectious disease as well as looking at tuberculosis and malaria. The idea is to provide a breakthrough in what typically required extensive cost, lots of lab work and long examination to be replaced with a low cost and easily administered solution. The application is very similar to taking a sample of mucous or saliva; this is sort of like a pregnancy test. We collaborate with large industrial partners such as GE Healthcare and hopefully we’ll be able to produce a commercially viable product in time.

TV: How are AVR Microcontrollers being used with the Arduino in your cosplay costume

ML: I use the ATmega168 (via the development and application of the Arduino Duemilanove board) for this costume. The microcontroller is used to control the color, power and timing of the lights on the costume through shift registers. The cosplay costume using this controller chip is the one pictured here.

I also use the ATmega328 (via the Arduino Uno/Uno R3 board) for the lab projects previously described. Specific tasks for the controller include driving the position and timing of a servo motor and/or linear actuator, as well as switching power on and off from an AC wall socket to a high powered, wide spectrum LED light source. Additionally, it was also used in a costume where it again controlled color, power and timing of LED’s, but these were driven using normal (non shift register) PWM signal controls. My costume using this controller chip is pictured here:

Figure 6: Photos by Mike Vickers

This is the ATmega32uF (via the Arduino Micro board) for my current project (in progress) that will be used for motor control.

* Mel’s costume is an original design inspired by a wide range of cyberpunk/fantasy artists including Masumune Shirow, Eric Canete, Joe Benitez and various modern gaming concept art. According to Mel, the process was a lot of fun and took approximately three months of on-and-off planning and building. The assembly is made from over 60 parts designed in Solidworks and sewn/cut/glued/laser-cut/heat-formed using various techniques. The costume includes color changing LEDs on the spine and front that are controlled by Arduino boards with Atmel AVR and ARM microcontrollers and onboard RGB controllers (respectively). The costume is powered by 16 AA batteries, 1 LiPo rechargeable battery, two 2032 coin cells and one 9-volt battery. In total, there are more than 70 LED’s on the entire costume and over 60 parts.

** Part one of this interview can be read here.

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1:1 Interview with Mel Li (Part 2)

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