Lab-on-a-chip, Microfluidics and Interfacial Electrokinetics

Chapter 1

Lab-on-a-chip, microfluidics and interfacial electrokinetics

The microfabrication technology has advanced microelectronics and computer technologies in an amazing speed, making the modem telecommunication and Internet technology possible, and consequently changed the way we work and the way we live profoundly, it allows rapid new technology development and dramatic cost reduction. Scientists and engineers have realized the tremendous advantages of the microfabrication technology and the enormous potential of applying the microfabrication technology to other fields such as mechanical engineering and biomedical engineering. This leads to the recent rapid development of Micro-Electro-Mechanical Systems (MEMS) and Laboratory-on-a-Chip (LOC) devices. A lab-on-a-chip (LOC) is a microscale chemical or biological laboratory built on a thin glass or plastic plate with a net work of microchannels, electrodes, sensors and electronic circuits. The width or the height of a typical microchannel ranges from 20 to 200 ~tm. Applying electrical fields through the electrodes along microchannels controls the liquid flow and other operations in the chip. These labs on a chip can duplicate the specialized functions as their room-sized counterparts, such as clinical diagnoses of bacteria and viruses, and DNA electrophoretic separation. The advantages of these labs on a chip include dramatic reduction in the amount of the samples and reagents, very short reaction and analysis time, high throughput, automation and portability [ 1-5]. In conventional chemistry and biology laboratories, an experiment is generally carried out as a series of separate operations (such as measuring samples, mixing solutions, and incubating) using separate tools and techniques. Many different instruments are involved from simple devices such as beakers, pipettes, stirring hot plate, centrifuge and incubator to more sophisticated instruments for PCR amplification, electrophoresis and fluorescent microscopy. Generally, the sample preparation prior to measurements is conducted manually and is labour intensive. Due to the relatively large size of the instruments, a large amount of the reagents or samples is required. This results in higher operating cost and longer time for completing the reaction and analysis. Conducting experiments with different samples or reagents require performing the costly and time-consuming separate experiments. These manual and individual experimental procedures may result in more chances for errors.

Electrokinetics in Microfluidics

A LOC device generally consists of a number of integrated microfluidic components such as pump, mixer, reactor, dispenser and separator, as illustrated in Figure 1. Therefore, multiple steps of an experiment can be conducted automatically on a single chip. For example, a sample of an unknown, singlestranded DNA solution and a solution containing a known, single-stranded DNA tagged with fluorescent dye are pumped from the reagent loading wells into a mixer by applying electric fields through the related electrodes. The mixed solution will then flow into a reactor where the unknown DNA fragments will react with the dye tagged DNA probe molecules (i.e., hybridization) at a specified temperature. The matched DNA samples will bind with the DNA probe. Following that, the reaction product will be pumped to the dispenser section. Then, by switching on another electrical field, a plug of DNA molecules will be dispensed into a buffer solution and flow into a separation micro channel where they are separated according to the charge to mass ratio by electrophoresis. Finally, when the separated DNA molecules enter the detection section of the microchannel, a laser beam is applied. The dye causes the DNA fragments to give off light when a laser beam is shone on them. The larger the separated fragment, the stronger the fluorescence. The detected light intensities are fed to a computer which sorts through signals from separated fragments to provide a sample analysis. Because of the size of the microchannels, the amount of the liquids involved in such a LOC is of the order of nanoliters, and hence the required amount of the samples and reagents are significantly less than that required in convemional lab experiments. Furthermore, using the microfabrication technology, we can easily make many parallel microchannel systems on a single chip, so that one chip can perform multiple tasks at the same time.

Figure 1.1.

Illustrationof microfluidic components in a lab-on-a-chip device.

Lab-on-a-chip, Microfluidics and Interfacial Electrokinetics

Currently, improving the technology and reducing the cost in health care is a major driving force for rapid development of LOC technology. The demand to apply LOC technology to genomics and proteomics research, high-throughput screening, drug discovery, point-of-care clinical diagnostic devices has been increasing remarkably over the last decade. There are many examples of the applications of LOC, including micro-total analysis system (~t-TAS) [6], microfluidic capillary electrophoretic separation [7,8], electrochromatography [9], PCR amplification [10-14], mixing [15,16], flow cytometry [17], sample injection of proteins for analysis via mass spectrometry [18-20], DNA analysis [21-24], cell manipulation [25], cell separation [26], cell patterning [27,28], fluid handling [29], immunoassay [30-37], enzymatic reactions [38-41 ], and molecular detection [42]. A recent review of integrated LOC devices can be found elsewhere [43] The most important media in the biomedical analysis and diagnostics are liquids. Common liquids used in LOC devices include whole blood samples, bacterial cell suspensions, protein or antibody solutions and various buffers. Therefore, a key to the functions of the LOC is the quantitatively controlled flow, mass (e.g., sample molecules and particles) transport and heat transfer processes in microchannels. The studies of the transport processes in microchannels are referred to as the microfluidics. Generally, a lab-on-a-chip device must perform the following microfluidic functions: pumping, metering, mixing, flow switching, thermal cycling or incubating, sample dispensing or injection, and separating molecules or particles, etc. Precise manipulation of these microfluidic processes is key to the operation and performance of LOC. Generally, we may classify the transport processes into three categories according to the characteristic dimension, Lc, of the systems: (1) Macroscale systems: Lc > 200 gm. (2) Microscale systems: 100 n m < Lc < 200 lam. (3) Nanoscale systems" Lc < 100 nm. The characteristics of the transport processes change significantly as the characteristic dimension of the system changes from one category to another category. It should be noted that microchannels have very large surface area to volume ratio. For example, for a microchannel of 100 ~tm in diameter, the surface area-volume ratio is" (27rRL/nR2L) - (2/R) = 2x 104 ( m - l ) . Therefore, one can expect significant influence of the liquidchannel wall interface on the microfluidic processes. Because most solid-liquid interfaces have electrostatic charge and consequently an electrical field near the interface, the interfacial electrokinetic phenomena are very important to microfluidic processes. In fact, most of the microfluidic processes on a LOC are electrokinetic processes. For example, electroosmosis is used to generate liquid motion or pump the liquid through microchannels; electrophoresis is used to separate molecules and particles in microchannels. Therefore, interfacial electrokinetic phenomena dominate these microscale transport processes.

Electrokinetics in Microfluidics

Because of the complex of the electrokinetic phenomena, the characteristics and controlling parameters of the microfluidic processes vary from system to system and from application to application. Conventional theories of the transport phenomena for macroscopic systems are generally not applicable in microfluidics. At the present, the lack of understanding of the complicated electrokinetic transport phenomena in microchannels makes it difficult to do systematic design and precise operation control of the labs on a chip. It is true that the microfabrication capability is needed to make a LOC device, one must realise that the fundamental understanding of the microfluidic transport processes is essential for the design and for the operation control of LOC devices. Therefore, this book is devoted to provide basic understanding of electrokinetic phenomena in some key microfluidic processes involved in LOC devices.

Lab-on-a-chip, Microfluidics and Interfacial Electrokinetics

REFERENCES

[1] [2] [3] [4] [5] [6]

[7]

[8]
[91 [10] [ 11] [12] [13] [ 14] [15] [16] [ 17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31 ] [32] [33]

J. Knight, Nature, 418 (2002) 474-5. M. Freemantle, Chemical & Engineering News, 77 (1999) 27-36. I. Wickelgren, Popular Science, Nov. 1998, 57-61. G. Sinha, Popular Science, Aug. 1999, 48-52. S. Borman, Chemical & Engineering News, Feb. 1999, 30-31. S.C. Jakeway, A.J. de Mello and E.L. Russell, Fresenius J. Anal. Chem., 366 (2000) 525-39. D.J. Harrison, K. Fluri, K. Seiler, K. Seller, Z. Fan, C. Effenhauser and A. Manz, Science, 261 (1993) 895-7. S.B. Cheng, C. D. Skinner, J. Taylor, S. Attiya, W. E. Lee, G. Picelli, and D. J. Harrison, Anal. Chem., 73 (2001) 1472-1479. R.D. Oelschuk, L.L. Shultz-Lockyear, Y. Ning and D. J. Harrison, Anal. Chem., 72 (2000) 585-90. M.U. Kopp, A.J. de Mello and A. Manz, Science, 280 (1998) 1046-8. D. Erickson and D. Li, Int. J. Heat Mass Transfer, 45 (2002) 3759-3770. P. Belgrader, M. Okuzumi, F. Pourahmadi, D.A. Borkholder and M. Northrup, Biosensors & Bioelectronics, 14 (2000) 849-852. J. Khandurina, et al., Anal. Chem., 72 (2000) 2995-3000. E.T. Lagally, I. Medintz and R.A. Mathies, Anal. Chem., 73 (2001) 565-570. A.D. Stroock, S.K.W. Dertinger, A. Ajdari, I. Mezic, H.A. Stone and G.M. Whitesides, Science, 295 (2002) 647-651. D. Erickson and D. Li, Langmuir, 18 (2002) 1883-1892. L.L. Sohn, et al., Proceedings of the National Academy of Sciences of the United States of America, 97 (2000) 10687-10690. D. Figeys, S.P. Gygi, G. McKinnon and R. Aebersold, Anal. Chem., 70 (1998) 37283734. Y. Jiang, P.C. Wang, L.E. Locascio and C.S. Lee, Anal. Chem., 73 (2001) 2048-2053. J. Gao, J.D. Xu, L.E. Locascio and C.S. Lee, Anal. Chem., 73 (2001) 2648-2655. B.A. Buchholz, et al., Anal. Chem., 73 (2001) 157-164. Z.H. Fan, et al., Analy. Chem., 71 (1999) 4851-4859. L. Koutny, et al., Anal. Chem., 72 (2000) 3388-3391. G.B. Lee, S.H. Chen, G.R. Huang, W.C. Sung and Y.H. Lin, Sensors and Actuators BChemical, 75 (2001) 142-148. I.K. Glasgow, et al., IEEE Transactions On Biomedical Engineering, 48 (2001) 570-578. J. Yang, Y. Huang, X.B. Wang, F.F. Becker and P.R. Gascoyne, Anal. Chem., 71 (1999) 911-918. D.T. Chiu, et al., Proceedings of the National Academy of Sciences of the United States of America, 97 (2000) 2408-2413. A. Folch, B.H. Jo, O. Hurtado, D.J. Beebe and M. Toner, J. Biomedical Materials Research, 52 (2000) 346-353. D.D. Cunningham, Anal. Chim. Acta, 429 (2001) 1-18. A. Hatch, et al., Nature Biotechnology, 19 (2001) 461-465. E. Eteshola and D. Leckband, Sensors and Actuators B-Chemical, 72 (2001) 129-133. S.B. Cheng, et al., Anal. Chem., 73 (2001) 1472-1479. T.L. Yang, S.Y. Jung, H.B. Mao and P.S. Cremer, Anal. Chem., 73 (2001) 165-169.

Electrokinetics in Microfluidics

[34] D.L. Stokes, G.D. Griffin and T. Vo-Dinh, Fresenius J. Anal. Chem., 369 (2001) 295301. [35] K. Sato, M. Tokeshi, T. Odake, H. Kimura, T. Ooi, M. Nakao and T. Kitamori, Anal. Chem., 72 (2000) 1144-7. [36] A. Dodge, K. Fluri, E. Verpoorte and N.F. de Rooij, Anal. Chem., 73 (2001) 3400-9. [37] M. Sharma, A. Saxena, S. Ghosh, J.C. Samantaray and G.P. Talwar, Indian J. Med. Res., 88 (1998) 409-15. [38] A.G. Hadd, D.E. Raymond, J.W. Halliwell, S.C. Jacobson and J.M. Ramsey, Anal. Chem., 69 (1997) 3407-3412. [39] D.C. Duffy, H. L. Gillis, j. Lin, N.F. Sheppard and G.J. Kellogg, Anal. Chem., 71 (1999) 4669-4678. [40] A.G. Hadd, S.C. Jacobson and J.M. Ramsey, Anal. Chem., 71 (1999) 5206-5212. [41 ] S.C. Jacobson and J.M. Ramsey, Anal. Chem., 68 (1996) 720-3. [42] B.H. Weigl and P. Yager, Science, 283 (1999) 346-7. [43] D. Erickson and D. Li, Anal. Chem. Acta, 507 (2004) 11-26.