Introduction To Microfluidics

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Write an essay on the development of Lab on Chip devices for point of care testing using at least two examples for reference, outlining the benefits of the technology. Indicate the success or potential for the technology in the area it is intended and describe any other applications. Highlight what you think are the barriers for these particular applications and what methods or actions could be used to overcome them.

Miniaturization of systems for life sciences has been done by a close interaction between biologists, engineers and doctors. Together, they have created Point of Care Testing. In this essay, the first part will concern the development of Lab on Chip devices for point of care testing. It will contain a study of the development of microfluidics and be illustrated by device examples already present in the market such as the pregnancy test, the glucose meter and the Flu detector. The second part will point out the benefit of the technology, analyzing its potential success, its barriers and points for improvement.

Point of care testing would not have existed without microfluidics. Tabeling [[1]] defines this subject as “the study of flows that are simple or complex, mono or multiphasic, which are circulating in artificial Microsystems”. Microfluidics is not only a science, but it is also a technology with concrete applications like point of care testing. The development of them is therefore intimately linked to microfluidics. Witesides [[2]] assumes that the microfluidics development technology has four origins: molecular analysis, biodefence, molecular biology and microelectronics. In fact, the success of microanalytical methods paved the way for the creation of concrete application in chemistry and biochemistry. A large part of the first financing projects to support microfluidics programs was accomplished by the US Department of Defense in order to answer to potential chemist and biological weapons after the cold war. Then, in the late 90s, DNA sequencing, and the development of genomics, as well as the development of the microelectronics, enabled the knowledge in microfluidics to be improved.

Analyzing living beings is one of the reasons for the development of microfluidics. The first concrete device was developed by Terry et al [[3]] in 1979. It was a gas chromatographic air analyzer fabricated on a silicon wafer. But it is only eleven years after that another one was made by Manz et al [[4]] creating the beginning of microTAS (micro total analysis systems). In order to be less restrictive than microTAS, the term “lab on chip” was created. In fact, a lab on chip can not have all of a lab in its chip, which is the case in a microTAS. Finally, the term “point of care testing” was created to define the ability to perform tests near the patients' bedside such as in a first aid ambulance, in the general practitioner's office or at home.

Basic points of care testing are not particularly new. For instance a test for the presence of blood in urine was commercialized in 1904 by the chemical company Helfenberg AG [[5]]. But over the past few years, analytical systems have increased considerably. Linked with the development of microfluidics, a wide range of tests can now be done. Three examples can accredit the goals of point of care testing: pregnancy tests, glucose meter and flu detection. In Great Britain, a pregnancy test can be bought in drugstore without prescription for a few pounds. This auto diagnostic tool gives the opportunity to women to determine if they are pregnant or not. It works by dosing the human chorionic gonadotropin hormone (HCG) which is secreted by the developing placenta when the fertilized egg implants in the uterine lining. This point of care system analyses in a few minutes a row sample (urine) and tells the result in a simple way (generally with color bars). This one-use test is fast, cheap, simple to use and accurate in more than 99% of cases [[6]]. The other example is the strips for testing glucose level in the blood used by the diabetics. A microlitre blood drop is analyzed by a little device. In few seconds, the glucose level appears on the numeric screen. This point of care costs less than £10 and the strips cost 50 pence each with the Accu-Check Aviva [[7]] device of the Roche Company for example. The last example is the flu analyzer. In March 2008, ST microelectronics created in collaboration with Veredus Laboratories a chip named VereFlu [[8]]. This point of care device can detect all major influenza types, including the H5N1 flu virus. In only two hours it provides genetic information of the infection which takes normally days to develop. That is the first one created for a rapid molecular flu detection at the point of need.

A point of care testing is a lab on a chip device. That means that all the characteristics of the latter can be applied to the former. Three main benefits can be analyzed due to the reduction of scales. The first interest is to improve performances and to save reagents and time. The second one is reduction in cost.

Using smaller volumes implies working with shorter distances. This allows to use less and rare expensive reagents. Miniaturization of devices is also the way to group more than one function in the same support and to create complete analyze chain. When all the functions are grouped together, there is less non-used volume due to a reduction of connectors. Furthermore, when a system is reduced, the contact between liquid and surface is higher. Therefore, the reactions are going faster. Systems are much more portable when they are smaller, which is an essential characteristic for point of care device. Lion et al [[9]] propose three main indicators to determine if a miniaturize system is more efficient, that is to say, performance, sample volume and time-to-result. They show that not all the time a miniaturized system is more useful but that microfluidics systems offer some clear advantages for some applications. For example, when a limited sample volume is available or when time-to-result is vital like in some first aid situations.

Integration of these systems on chips gives the opportunity to build them on very large scales. Lab-on-chip devices are built using the same technique as for microelectronics. This increases the reproducibility and decreases the cost. Therefore, those costs can be really cheap and permit the creation of disposable devices for a unique use, deleting at the same time problems of contamination. This also gives the opportunity to get patient analysis in low medical infrastructure sites like in the developing nations which do not dispose of expensive analysis machines [[10]]. Furthermore, point of care testing gives a faster result than using a laboratory. This may reduce the number of consultations and may reduce the length of hospital stay as well. Although laboratory testing is less expensive than point of care testing, it produces economic benefits with more rapid treatment and discharge. Furthermore, the reduction of stress due to the expectation of answer by the patient is an important point to help him to recover.

Some difficulties mean that some parts of technology have to be improved. The first one is scale reduction. In fact, it is not sufficient to reduce the dimensions homothetically. For example, miniaturization implies the increase of the surface/volume ratio. This can be positive to increase time reaction, but also can be negative. In fact, absorption of liquid by the sides or evaporation of liquids can be occurred. Studying surface composition is therefore crucial. Also, miniaturization makes it difficult for the fluid to move and mix. Creating more effective pumps and mixers will therefore help to make more effective point of care devices. User acceptance as well as reliability have also to be continuously improved in order to develop commercially point of care testing.

To conclude, we have seen that, currently, scientists work to miniaturize diagnostic devices in order to create new ones which are more portable, disposable and independent. These devices also have to be faster and cheaper. Point of care testing devices are, by definition, as near as possible to the patient and when the analyses are performed at home, the patient can eventually give the result to his general practitioner online. The other objectives are to make the patient's life easier and to increase health quality. Treatment starts when the illness is identified; the more advanced the scientists are, the quicker the illness is detected. This will help doctors to be more accurate with regard to the patient's treatment.

  1. Tabeling, introduction to microfluidics, page 1;
  2. G.M. Whitesides: The origins and the future of microfluidics. Nature, 442, 368-373 July 2006, doi:10.1038/ nature05058
  3. S.C. Terry, J.H. Jerman, J.B. Angell, «A gas chromatographic air analyzer fabricated on a silicon wafer», IEEE Transactions on Electron Devices, vol.26, no12, Dec. 1979, p.1880-1886 ;
  4. A. Manz, N. Graber, H.M. Widmer, «Miniaturized total chemical analysis systems: A novel concept for chemical sensing», Sensors and Actuators B, vol.1, no1-6, Jan. 1990, p.244-248 ;
  5. Roche, Compendium Urinalysis, Urinalysis with Test Strip, page 6 - http://www.scribd.com/doc/15794604/Urine-Strips 02/12/2009 ;
  6. Phillips, Pat (2007). “Early Pregnancy Tests”. Pregnancy Test FAQ, http://www.early-pregnancy-tests.com/pregnancy-tests.html#accurate, 02/12/2009 ;
  7. Roche, https://www.accu-chek.com/us/glucose-meters/aviva.html, 02/12/2009 ;
  8. ST Microelectronics, http://www.st.com/stonline/stappl/cms/press/news/year2008/t2277.htm, 02/12/2009 ;
  9. Niels Lion, Frederic Reymond, Hubert H Girault, Joel S Rossier, Why the move to microfluidics for protein analysis?, Current Opinion in Biotechnology, Volume 15, Issue 1, February 2004, Pages 31-37, doi:10.1016/j.copbio.2004.01.001 ;
  10. P. Yager, T. Edwards, E. Fu, K. Helton, K. Nelson, M.R. Tam, B.H. Weigl, Microfluidics diagnostic technologies for global public health. Nature, 442: 412-418, July 2006, doi: 10.1038/nature05064.

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