“Fluidics” is the information extracted from bodily fluids and the understanding of liquids or fluids using small diameter volumes. Hippocrates (400 BC), Galen (200 AD) and Theophilus (700 AD) were interested in analyzing urine samples — to understand the human body and its functions (1). They compared and analyzed urine color, corresponding to patients’ symptoms. About 1000 years later, scientists worked on the behavior of fluids using glass containers with small volume and diameters.

A microfluidic chip is a set of micro-channels molded into a material (most commonly: glass, silicon, gel or polymers such as PDMS). The micro-channels forming the microfluidic chip are connected together in order to achieve desired features for the chip (e.g., sort, mix, flow speed control, to name a few). This network of micro-channels trapped into the microfluidic chip is connected to the outside world via inputs or outputs connected through the chip. Currently, using new materials for microfabrication and nanofabrication, scientists can confine fluids to micro- or nano-channels. In addition to fluids, cells, tissues, and even organ-like miniatures can be investigated inside the microfluidic chips.

Here are the most notable publications to illustrate the development of microfluidic chips:

1) In 1993, Andreas Manz’s research group published an article describing the fabrication of a miniaturized capillary electrophoresis-based chemical analysis system — 1cm by 2cm. (1);

2) In 1998, George Whitesides’ lab group published an article on rapid prototyping of microfluidic systems using polydimethylsiloxane (PDMS) (1);

3) In 2000, an article was published describing discrete liquid droplets accomplished by direct electrical control of the surface tension (1). This was the first example of the liquid handling technique that allows the control of piciliter- to microliter-sized droplets (1);

4) In 2007, Whiteside’s group described a paper-based, portable, low-cost alternative for bioassay microfluidic devices (1)– millimeter-sized channels with hydrophilic and hydrophobic zones, transporting fluids without the need for pumps due to capillarity effects;

5) Around 2013-2014, 3D imprinting was first published. This is most relevant to studies involving cells, tissues and organs-on-chips (2, 3);

Moving forward and future perspectives: 

Even though microfluidic technologies offer great potentials for 3D cell culture and a variety of biomedical applications, their limitations and challenges are pronounced (3). For example, “access to LIVE cells during an assay” and “miniaturization of chips” remain difficult problems to solve. Microfabrication, manufacturing (scale-up), and commercialization of microfluidic chips remain costly for scientists (especially, academic scientists). These notable challenges remain as barriers for scientists to advance biomedical science using microfluidics.

References:

1) Castillo-León J. (2015) Microfluidics and Lab-on-a-Chip Devices: History and Challenges. In: Castillo-León J., Svendsen W. (eds) Lab-on-a-Chip Devices and Micro-Total Analysis Systems. Springer, Cham.

2) Edmond W. K. Young, Cells, tissues, and organs on chips: challenges and opportunities for the cancer tumor microenvironment, Integrative Biology, Volume 5, Issue 9, September 2013, Pages 1096–1109.

3) Li XJ, Valadez AV, Zuo P, Nie Z. Microfluidic 3D cell culture: potential application for tissue-based bioassays. Bioanalysis. 2012;4(12):1509-1525.