Nanoholes and Nanoparticles: Applications to Biomedical Microdevices

Biomedical microdevices include any miniaturized devices or systems for biomedical or biological applications, from simple sensors for monitoring a single biological, to complex micro total analysis or lab-on-a-chip instruments that integrate multiple laboratory functions together with microfluidic sample manipulation. Biomedical microdevice and systems research is an exciting multi-disciplinary field intersecting engineering, physics, chemistry, nanotechnology and biotechnology.

Micromachining, originally based in the microelectronic industry, forms the foundation for this exciting field, in which biosensors, microchannel fluid transport, and other micro mechanical, optical, chemical, and fluidic components are fabricated and integrated for applications ranging from monitoring biofluid levels and bed side rapid diagnosis to studying single cell antibody production. Furthermore, micromachining can be combined with nanostructures or nanomaterials to result in new technologies and techniques that continue to advance the field in new ways.

The Microinstrumentation Lab (µiL) at Simon Fraser University (SFU), under the direction of Professor Bonnie Gray, develops a wide variety of biomedical microdevice and system technologies and techniques. While conventional silicon is still employed, micromachining of polymers and glass has taken center stage driven by applications in biomedicine and biology.

Polymers can be employed for highly flexible microinstrumentation that can conform to the body or other surfaces, that is optically transparent, biocompatible, with inexpensive prototyping and easy micropatterning (e.g., micromolding, uv-light photopatterning). Glass is similarly optically transparent and biocompatible, and makes an excellent substrate for polymer microstructures.

Researchers at Microinstrumentation Lab (µiL) are developing free-standing snap-together polymer microfluidic systems with flexible electronic interconnect and on-board microactuators for micropumps and valves. While thin film metal-on-polymer techniques have been successfully demonstrated for electronic routing¹, another approach avoids mechanical materials mismatch by employing hybrid combinations of insulating polymers with conductive nanocomposite polymers (C-NCPs). While flexible polymers are inherently electrically insulating, conducting nanoparticles added to a polymer matrix result in conduction once the percolation threshold has been reached².

The Microinstrumentation Lab (µiL) is developing new techniques to micropattern complete functional systems using hybrid combinations of conducting and nonconducting polymers (Figure 1). In addition to conductive polymers, magnetic polymers can be realized with the addition of magnetic nanoparticles to a flexible polymer matrix. Such magnetic polymers are employed by Microinstrumentation Lab (µiL) for assisting in micro peg-in-hole chip-to-chip microassembly³, or on-chip fluid manipulation⁴.

Figure 1. Flexible conductive nanocomposite polymer embedded in an insulating flexible polymer circuit board for microfluidic component.

Nanotechnology also features in the development of novel biosensors integrated with microfluidics at Microinstrumentation Lab (µiL). One new sensor is based on the modification in light transmission through an array of nanoholes using surface plasmon resonance (SPR). A surface plasmon is a wave along the interface of a dielectric and a metal⁵, with a periodic array of nanoholes dramatically enhancing certain wavelengths of transmitted light while attenuating others⁶.

Transmission SPR sensors can be employed to detect changes in surface chemistry, such as the adsorption of a biological species to the metal nanohole surface, resulting in a shift in wavelength at which surface plasmons excite and peak of transmission. By integrating the nanohole arrays with microfluidics, samples can be easily flowed past the sensor⁷ (Figure 2).

Figure 2. Top down photograph of enclosed microchannel with integrated snap-in-place interconnect structures and gold nanohole array. The inset shows a close-up scanning electron microscope image of a nanohole array with period = 500 nm.

Furthermore, Microinstrumentation Lab (µiL) researchers are trapping large arrays of individual cells to monitor single cell antibody response. Antibodies emanating from each cell attach to adjacent SPR sensors, one per cell, resulting in changes in surface plasmon generation and transmission. This collaboration between engineers, physicists, chemists, and immunologists employs microfluidics and nanotechnology to help understand immunological processes through real-time monitoring of individual cells.

In addition to the SPR nanohole array sensor, nanotechnology and microfabrication are jointly employed by Microinstrumentation Lab (µiL) researchers for flexible electroenzymatic sensors for monitoring tear glucose levels (Figure 3)⁸, which are approximately 1/40 of blood glucose levels but do not require painful pin prick blood sampling. The sensors are fabricated on flexible polymer substrates suitable for implantation in contact lenses, with active electrode surfaces modified with combinations of nanostructured surfaces and enzyme immobilization of glucose oxidase, which produces an electronic signal that is proportional to glucose level.

Figure 3. Flexible gold-on-polymer electroenzymatic glucose sensors.

References

1. J.N. Patel, B. Kaminska, B.L. Gray, B.D. Gates, "A sacrificial SU-8 mask for direct metallization on PDMS", Journal of Micromechanics and Microengineering, 19:11, 115014 (10pp), 2009.
2. A. Khosla, B.L. Gray, "Preparation, Characterization, and Micromoulding of Multi-walled Carbon Nanotube Polydimethylsiloxane Conducting Nanocomposite Polymer", Materials Letters, 63:13-14, pp. 1203-1206, 2009.
3. S. Jaffer, B.L. Gray, D.G. Sahota, M.H. Sjoerdsma, "Mechanical assembly and magnetic actuation of polydimethylsiloxane-iron composite interconnects for microfluidic systems", Proceedings of SPIE, vol. 6886, January 2008, 12 pages.
4. A. Khosla, B. L. Gray, D. B. Leznoff, J. Herchenroeder, D. Miller, "Fabrication of integrated permanent micromagnets for microfluidic systems", accepted to SPIE Photonics West, January 2010, San Jose.
5. R. Gordon, A.G. Brolo, K.L. Kavanagh, D. Sinton, J. Pond, "Understanding the extraordinary optical properties of nanohole arrays in metals," Photons, vol. 2, pp. 15-18, 2004.
6. T.W. Ebbesen, H.J. Lezec, H.F. Ghaemi, T. Thio, P.A. Wolff, "Extraordinary optical transmission through sub-wavelength hole arrays," Nature, vol. 391, pp. 667-669, 1998.
7. S. M. Westwood, B. L. Gray, S. Grist, K. Huffman, S. Jaffer, K. L. Kavanagh, "SU-8 Polymer Enclosed Microchannels with Interconnect and Nanohole Arrays as an Optical Detection Device for Biospecies", IEEE 30th Annual Engineering in Medicine and Biology Conference, Vancouver, August 2008, 4 pages.
8. J. Patel, B. Kaminska, B. L. Gray, B. D. Gates, "SU-8 as a peel-off mask for reliable metallization on PDMS for an electro-enzymatic glucose sensor", Fifth International Conference on Microtechnologies in Medicine and Biology, Quebec City, April 2009.