Electrochemical Biosensors and Microfluidics in Organic System-on-Package Technology

A nanobioelectronic system-on-package (SOP) with integrated electrochemical sensors, microfluidic channels and microneedles was demonstrated with organic compatible processes. A novel amperometric glucose sensor based on carbon nanotubes/glassy carbon working electrodes and glucose oxidase enzyme encapsulated in a sol-gel derived zirconia/nafion matrix was developed to demonstrate the biosensing. The sol-gel chemistry provides an attractive way to immobilize the sensitive biomolecules on the electrode at low temperatures. The amperometric measurements were carried out with a three-electrode system. SU8 epoxy based thick microfluidic channels were built over the electrode layer and then the enzyme was immobilized, followed by sealing of the channel with a PDMS membrane using a low temperature bonding process (60degC). The enzyme-catalyst reaction was recorded as the release of electrons from the oxidation of glucose into gluconolactone, hydrogen peroxide and subsequently into water. The results indicate that the response time is within few seconds. The current varied from 1 muA to 2.5 muA as the glucose concentration was increased from 5 mM to 20 mM. Finally, a compatible microneedle technology is demonstrated to enable transdermal fluid injection into the device for real-time health monitoring. Nanobio SOP with recent advances in nanobiosensing, nanomedicine, low-cost polymer-based high-density packaging, mixed-signal electronics can lead to the portable, reliable and cost effective biomedical devices of the future.

[1]  G. C. Wall.  THE SOL-GEL PROCESS , 1965 .

[2]  L. Hench,et al.  The sol-gel process , 1990 .

[3]  S. Iijima.  Helical microtubules of graphitic carbon , 1991, Nature.

[4]  Pulickel M. Ajayan,et al.  Carbon nanotube electrode for oxidation of dopamine , 1996 .

[5]  Richard J. Coles,et al.  Protein electrochemistry at carbon nanotube electrodes , 1997 .

[6]  Soichi Yabuki,et al.  Glucose oxidase/polyion complex-bilayer membrane for elimination of electroactive interferents in amperometric glucose sensor , 1998 .

[7]  Herbert Wolter,et al.  Synthesis, properties and applications of inorganic–organic copolymers (ORMOCER®s) , 1999 .

[8]  Angel Rubio,et al.  Improved Charge Transfer at Carbon Nanotube Electrodes , 1999 .

[9]  Peter M. Martin,et al.  Laminated plastic microfluidic components for biological and chemical systems , 1999 .

[10]  Karl-Heinz Haas,et al.  Hybrid Inorganic–Organic Polymers Based on Organically Modified Si-Alkoxides , 2000 .

[11]  G. Harsányi,et al.  Sensors in Biomedical Applications: Fundamentals, Technology and Applications , 2000 .

[12]  Yong Liu,et al.  Multiphoton-absorbing organic materials for microfabrication, emerging optical applications and non-destructive three-dimensional imaging , 2000 .

[13]  J. Kong,et al.  Probing trace phenols based on mediator-free alumina sol--gel-derived tyrosinase biosensor. , 2000, Analytical chemistry.

[14]  Iqbal Gill,et al.  Bio-doped Nanocomposite Polymers: Sol-Gel Bioencapsulates , 2001 .

[15]  S. Tan,et al.  Amperometric hydrogen peroxide biosensor with silica sol-gel/chitosan film as immobilization matrix , 2001 .

[16]  C. Splieth,et al.  Polymerization shrinkage-strain and microleakage in dentin-bordered cavities of chemically and light-cured restorative materials. , 2002, Dental materials : official publication of the Academy of Dental Materials.

[17]  Boris N. Chichkov,et al.  Inorganic–Organic Hybrid Polymers for Information Technology: from Planar Technology to 3D Nanostructures , 2003 .

[18]  B N Chichkov,et al.  Femtosecond laser-induced two-photon polymerization of inorganic-organic hybrid materials for applications in photonics. , 2003, Optics letters.

[19]  S. Yoon,et al.  A novel multi-walled carbon nanotube-based biosensor for glucose detection. , 2003, Biochemical and biophysical research communications.

[20]  H. Darmani,et al.  Cytotoxicity evaluation of dental resin composites and their flowable derivatives , 2005, Clinical Oral Investigations.

[21]  Mark R Prausnitz,et al.  Microneedles for transdermal drug delivery. , 2004, Advanced drug delivery reviews.

[22]  J. Roulet,et al.  Color stability of resin matrix restorative materials as a function of the method of light activation. , 2004, European journal of oral sciences.

[23]  Aleksandr Ovsianikov,et al.  Fabrication of woodpile structures by two-photon polymerization and investigation of their optical properties. , 2004, Optics express.

[24]  Won-Yong Lee,et al.  Amperometric glucose biosensor based on sol–gel-derived metal oxide/Nafion composite films , 2005 .

[25]  L. Y. Lim,et al.  Influence of dietary solvents on strength of nanofill and ormocer composites. , 2005, Operative dentistry.

[26]  Won-Yong Lee,et al.  Amperometric Glucose Biosensor Based on Sol-Gel-Derived Zirconia/Nafion Composite Film as Encapsulation Matrix , 2006 .

[27]  B. Chichkov,et al.  Two photon induced polymerization of organic-inorganic hybrid biomaterials for microstructured medical devices. , 2006, Acta biomaterialia.