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September 1, 2016

Honey, I Shrunk the Lab!

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Aside from the perennially famous ‘death and taxes,’ there are two other givens in our modern world: continual miniaturization and impoverished eyesight. It might, in fact, be contended that one precedes the other but that would be a discussion for a different kind of post. In this one, however, we are excited to take a look at a spectacular new development in the manufacturing of a decidedly 21st century miniaturization technology:

the Lab-on-a-Chip, or LOC.

Grounded in the technology of photolithography, basic LOCs have actually been around for a surprisingly long while. The mid-60s saw early prototypic technology applied to pressure sensor manufacturing and as our understanding in creating mechanical structures on the sub-micrometer scale for silicon wafers grew, the race began. Within little more than a decade, LOC research had developed to the point that micropumps and flow sensors – critical to fluid analysis – were within reach. And mastery of these technologies was the cornerstone upon which modern lab analysis on a chip was built. The 1990s flurry of interest in the field of genomics coupled with the US military’s need to create portable and effective devices to detect bio- or chemical warfare agents led to the much needed funding boost for research, and the LOC as we now know it was born.

So what exactly is this device? Put simply it’s a type of micro-electric-mechanical-system (MEMS) that can analyze sample of fluids on a pico-liter level. Pico-liter? That’s one trillionth, or 0.000000000001, of a liter. The chip can perform single or multiple processes that are normally reserved only for a laboratory or cleanroom setting. An example of such analyses might be that of capillary electrophoresis, where sample saliva is migrated through the capillary via electrostatic action and is analyzed for specific ions. Not sure how this humble test might be useful? According to Professor Norman J. Dovichi of the University of Alberta, Canada, it played a significant role in sequencing the human genome.(1) Or, on a more personalized level, chips can also perform monitoring tests for blood lithium levels in bipolar patients, create accurate sperm counts, or check sodium levels in patients with kidney dysfunction.(2)

And all of this is done on a chip that’s anywhere from a few millimeters to a couple of square centimeters in size – with the largest being roughly the size of a standard shirt button.

So what are these LOCs made of? Acknowledging their semi-conductor origins, modern units were initially created from silicon but new processes allow them to be manufactured from a variety of materials including glass, metal, ceramics, polymers, and via injection molding. Using this variety of materials has clear cost benefits and broadens the scope and speed of production. And as the technology has matured and additional materials have come on line in manufacturing, the demand for cheap and easy-to-use devices has grown.

Despite a couple of drawbacks to the still comparatively new technology (detection principles may not scale perfectly leading to low signal-to-noise ratios, for instance), the advantages are very clear and fall into a triumvirate of categories: resource conservation, ease of use, and cost efficiency. In a field operation such as an ebola outbreak like that of 2014 in Liberia, conditions may be less than ideal. Commonly used resources such as chemical reagents may be in short supply or power generation might be compromised and the ability to run lab-like analysis in situ without the need for a full lab or cleanroom is critical. Also, where the fluids under test are potentially harmful or life-threatening (ebola or any of the avian influenza strains, for instance), taking as conservative a sample as possible is desirable. Let’s remember that microfluidics deal with the manipulation of very small quantities of fluid – and in the case of nanofluidics, even just a few individual macromolecules in solution.(3) And with a smaller sample size comes the reduced need for stored energy making the LOC a safer analytic platform.

In addition, in a highly-stressed arena such as that of an epidemic outbreak or contained areas such as prisons, crime scenes, or even schools where a full laboratory or cleanroom is not available and off-site transportation of samples is an issue, ease of use comes to the forefront. The compact form of an LOC allows analysis that is faster due to shorter diffusion distances (the distances analytes need to travel during the test) and enhanced thermal control. And finally, the cost consideration is always…a consideration. When compact systems that integrate dual or multiple functionality are produced through mass manufacturing, the lower associated cost per unit allows for disposability. And since biological/medical waste is not recyclable, the smaller the item with the least volume of chemical waste, the better for the environment.

But is the technology to produce these labs-on-a-chip available to organizations outside of the government and the military. The short answer is yes. In December of this year, the ‘Lab-on-a-Chip Asia’ conference will be held in Singapore with confirmed speakers drawn from fields of academia and industry, from the United Kingdom to Korea to Japan. And many places in between.(4) And this meeting, entitled Microfluidics, Point-of-Care Diagnosis, and Organ-on-a-Chip is the fourth annual conference – a sure sign of on-going market interest.

Injection Molding and Cleanroom Technology

And potentially to that end injection molding manufacturer Wittmann Battenfeld, a part of the Austrian Wittmann group which has bases on no fewer than five continents, has recently taken the step of opening a state-of-the-art demonstration cleanroom in Torrington, CT.(5) Slated to be debuted at an Innovations Open House in October 2016, the 62-square meter cleanroom will house two injection molding machines – an EcoPower SE 110/350 and a MicroPower 15/10 molding press. The MicroPower, a toggle machine that specializes in producing high-precision small and micro parts, will be fully outfitted with a cleanroom module, in effect making it a self-contained cleanroom. In addition to these ultra high-tech injectors, a W821 linear robot – an automated arm on a travel bar driven by a servomotor – will also be available. Worldwide, Wittmann Battenfeld serves several industry silos, one of which is medical technology with the LOCs joining its existing stable of thermally-extruded medical devices, including dosage spoons for liquid medications and lances for monitoring blood sugar levels in diabetic patients.(6) Given the vaunted 30% – 50% cost savings when using the MicroPower molding press, Wittmann Battenfeld might indeed be a player to watch in the expanding market.(7)

Think that the future of lab analyses lies on the end of a microchip? Or will full-scale cleanrooms and laboratories always be necessary? We’d love to hear your thoughts! Please make a note in the Comments section below.

References:

1. http://www.chem.ualberta.ca/~campbell/resources/Bioanalytical-2012/dovichi_review.pdf
2. http://www.news-medical.net/life-sciences/Health-Applications-of-Lab-on-a-Chip.aspx
3. http://www.azonano.com/article.aspx?ArticleID=3081
4. https://selectbiosciences.com/conferences/index.aspx?conf=LOACA2016
5. http://www.prw.com/article/20160825/PRW/160829923/wittmann-battenfeld-opens-demonstration-clean-room
6. http://www.wittmann-group.com/en_us/industries/medical-technology.html
7. Compared to standard machines. http://www.wittmann-group.com/en_us/injection-molding/toggle-machines/micropower-5-15.html

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