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RESEARCH

Background

Miniaturized devices have had a significant impact on our society in revolutionizing the electronics industry. A similar trend of size-reduction is emerging in the health care industry to produce small bioanalytical devices for disease diagnosis, novel methods for drug delivery to treat diseases, and microfabricated platforms for studying microorganisms. Nanostructured materials, in particular, have revolutionized capabilities of biotic-abiotic interfaces in various biomedical devices, including affinity biosensors, implantable neural electrodes, drug delivery platforms, and in vitro models. Despite the recent research on these materials, significant challenges remain in controlling material properties, interfacing nanocomponents with instrumentation, and engineering their interaction with biological systems.

Prior to joining UC Davis as a faculty member, Şeker’s dissertation focused on microfabrication and thermo-mechanical characterization of nanoporous gold [1,2], a promising candidate for functional surface coatings due to its controllable morphology, electrical conductivity, and well-studied gold surface chemistry [3]. In addition, he studied mass-transport in porous media[4] and synthesized a composite material that exhibits very low elastic modulus and high electrical conductivity [5] – highly desirable attributes for flexible electrodes. As a postdoctoral researcher in chemistry department, his research extended to the study of biomolecule-surface interactions [6] and development of novel flow control methods in microfluidic circuits [7,8].  As a research associate at Center for Engineering in Medicine (CEM), he began to utilize nanoporous metals for developing planar multiple electrode arrays for electrophysiology applications [9].

The overarching objective of our group is to utilize our expertise at the intersection of nanoporous metal synthesis, microfluidics, and device engineering to overcome challenges in the evolution of miniaturized devices relevant to microelectronics and life sciences. We gratefully acknowledge support from National Science Foundation (1512745, 1454426, 2003849), UC Lab Fees Research Program (12-LR-237197), National Institutes of Health (T32-GM008799, R21-EB024635, R21-AT010933, R03-NS118156, R03-NS118156-S1), UC Davis Research Investments in the Sciences and Engineering (RISE), UC Davis Comprehensive Cancer Center, and UC Davis Microbiome Special Research Program.

The projects listed below are a selected group of our current research thrusts, which are also summarized in a short video. Please contact Prof. Erkin Şeker for more information.

Main Research Thrusts

Nanostructured Electrochemical Biosensors

An integral component of a biosensor platform with an electrochemical read-out is the sensor element that interfaces biomolecular detection probes with instrumentation electronics. Sensor performance, on both biomolecular and electrical levels, is strongly influenced by sensor coating properties, such as morphology, surface chemistry, and metallurgy. While nanostructured materials have shown significant promise in enhancing the performance of these sensors, the underlying mechanisms for this enhancement are not fully understood.

Currently, we are fabricating novel nanostructured electrodes to provide insight into how nanoscale features enhance sensitive measurement and purification of nucleic acids in complex biological samples [10-18]. The fundamental studies will reveal a set of design rules for the development of nanostructured electrochemical sensor elements and assist technological advancements in food safety, water quality, and medical diagnostics.

Tunable nanoporous gold morphology

Multifunctional Biomedical Device Coatings

There is a significant need for medical devices that can both monitor and modulate physiological activity, while minimizing adverse tissue response to an implant. This is particularly important in neurological disorders, since neurons exhibit both electrical and chemical activity as a part of their normal function and implanted neural interfaces typically suffer from deteriorating device performance due to tissue-material interactions.

Currently, we are creating multifunctional neural electrodes that incorporate tunable drug delivery and topographical cues. Specifically, we focus on the fundamentals of molecular release from nanoporous metals [19-22] and cell-surface interactions as a function of nano-topography [23-25]. We expect that these efforts will translate into advanced neural interfaces for closed-loop control of neurological disorders such as epilepsy.

Astrocyte adhering onto porous surface

Nanoporous Metal Morphology Libraries

In the studies described above, nanoporous metal attributes (e.g., characteristic feature size, effective surface area, electrical conductivity, and surface chemistry) translate into several key device performance metrics: (i) limit of detection, sensitivity, and biofouling-resilience of affinity biosensors; (ii) biocompatibility, signal-to-noise ratio, and charge injection capacity of neural electrodes; and (iii) loading capacity, release kinetics, and on demand release in drug delivery platforms.

Currently, we are developing techniques to modulate pore morphology (via electro-thermo-mechanical mechanisms) and surface chemistry with the goal of creating on-chip libraries that display multiple material attributes [14,26-29]. We expect these libraries to allow for high-throughput study of structure-property relationships in the context of biomolecule-tissue-material interactions, as well as other applications such as catalysis and energy storage.

Freestanding nanoporous gold beam array

Microphysiological Models

Inflammation plays a key role in numerous conditions, including degenerative diseases, cancer, brain injury, Crohn's disease, and metabolic disorders. Gut microbiota adds another level complexity to the picture, where bacterial metabolites modulate inflammation and neural activity. There are still many unknowns on the mechanisms of how inflammation traverse large anatomical distances and how gut microbiota and the nervous system interact. 

Currently, we are integrating our sensing and actuation technologies with microfluidics and novel cell culture approaches to engineer microphysiological models of neuroinflammation and enteric epithelium-neuron interaction [30-32]. These models, in turn, allow us to study the transmission modes of inflammation in the central nervous system and influence of bacterial metabolites. We expect these platforms to facilitate rapid testing of therapeutics and provide insight into unique physiological phenomena observed in vivo.

Tissue chip with multifunctional electrodes

Reference Papers

1.     Seker, E., Gaskins, J., Bart-Smith, H., Zhu, J., Reed, M., Zangari, G., Kelly, R. & Begley, M. The effects of post-fabrication annealing on the mechanical properties of freestanding nanoporous gold structures. Acta Materialia 55:4593 (2007).

2.     Seker, E., Reed, M. L. & Begley, M. R. A thermal treatment approach to reduce microscale void formation in blanket nanoporous gold films. Scripta Materialia 60:435 (2009).

3.     Seker, E., Reed, M. & Begley, M. Nanoporous Gold: Fabrication, Characterization, and Applications. Materials 2:2188 (2009).

4.     Seker, E., Begley, M., Reed, M. & Utz, M. Kinetics of capillary wetting in nanoporous films in the presence of surface evaporation. Applied Physics Letters 92:013128 (2008).

5.     Seker, E., Reed, M., Utz, M. & Begley, M. Flexible and conductive bilayer membranes of nanoporous gold and silicone: Synthesis and characterization. Applied Physics Letters 92:154101 (2008).

6.     Huang, L., Seker, E., Landers, J., Begley, M. & Utz, M. Molecular Interactions in Surface-Assembled Monolayers of Short Double-Stranded DNA. Langmuir 26:11574 (2010).

7.     Leslie, D., Easley, C., Seker, E., Karlinsey, J., Utz, M., Begley, M. & Landers, J. Frequency-specific flow control in microfluidic circuits with passive elastomeric features. Nature Physics 5:231 (2009).

8.     Seker, E., Leslie, D., Haj-Hariri, H., Landers, J., Utz, M. & Begley, M. Nonlinear pressure-flow relationships for passive microfluidic valves. Lab on a Chip 9:2691 (2009).

9.     Seker, E., Berdichevsky, Y., Begley, M., Reed, M., Staley, K. & Yarmush, M. The fabrication of low-impedance nanoporous gold multiple-electrode arrays for neural electrophysiology studies. Nanotechnology 21:125504 (2010).

10.   Daggumati, P., Matharu, Z. & Seker, E. Effect of Nanoporous Gold Thin Film Morphology on Electrochemical DNA Sensing. Analytical Chemistry 87:8149 (2015).

11.   Daggumati, P., Matharu, Z., Wang, L. & Seker, E. Biofouling-resilient nanoporous gold electrodes for DNA sensing. Analytical Chemistry 87:8618 (2015).

12.   Daggumati, P., Appelt, S., Matharu, Z., Marco, M. & Seker, E. Sequence-Specific Electrical Purification of Nucleic Acids with Nanoporous Gold Electrodes. Journal of the American Chemical Society 138:7711 (2016).

13.   Zhou, J. C., Feller, B., Hinsberg, B., Sethi, G., Feldstein, P., Hihath, J., Seker, E., Marco, M., Knoesen, A. & Miller, R. Immobilization-mediated reduction in melting temperatures of DNA–DNA and DNA–RNA hybrids: Immobilized DNA probe hybridization studied by SPR. Colloids and Surfaces A: Physicochemical and Engineering Aspects 481:72 (2015).

14.   Matharu, Z., Daggumati, P., Wang, L., Dorofeeva, T. S., Li, Z. & Seker, E. Nanoporous-Gold-Based Electrode Morphology Libraries for Investigating Structure–Property Relationships in Nucleic Acid Based Electrochemical Biosensors. ACS applied materials & interfaces 9:12959 (2017).

15.   Veselinovic, J., Alangari, M., Li, Y., Matharu, Z., Artés, J. M., Seker, E. & Hihath, J. Two-tiered electrical detection, purification, and identification of nucleic acids in complex media. Electrochimica Acta 313:116 (2019).

16.   Veselinovic, J., Li, Z., Daggumati, P. & Seker, E. Electrically Guided DNA Immobilization and Multiplexed DNA Detection with Nanoporous Gold Electrodes. Nanomaterials 8:351 (2018).

17.   Veselinovic, J., AlMashtoub, S., Nagella, S. & Seker, E. Interplay of Effective Surface Area, Mass Transport, and Electrochemical Features in Nanoporous Nucleic Acid Sensors. Analytical Chemistry (2020).

18.   Veselinovic, J., Almashtoub, S. & Seker, E. Anomalous trends in nucleic acid-based electrochemical biosensors with nanoporous gold electrodes. Analytical Chemistry 91:11923 (2019).

19.   Seker, E., Berdichevsky, Y., Staley, K. J. & Yarmush, M. L. Microfabrication-Compatible Nanoporous Gold Foams as Biomaterials for Drug Delivery. Advanced Healthcare Materials 1:172 (2012).

20.   Kurtulus, O., Daggumati, P. & Seker, E. Molecular Release from Patterned Nanoporous Gold Thin Films. Nanoscale 6:7062 (2014).

21.   Polat, O. & Seker, E. Halide-Gated Molecular Release from Nanoporous Gold Thin Films. The Journal of Physical Chemistry C 119:24812 (2015).

22.   Li, Z., Polat, O. & Seker, E. Voltage‐Gated Closed‐Loop Control of Small‐Molecule Release from Alumina‐Coated Nanoporous Gold Thin Film Electrodes. Advanced Functional Materials:1801292 (2018).

23.   Chapman, C. A., Chen, H., Stamou, M., Biener, J., Biener, M. M., Lein, P. J. & Seker, E. Nanoporous Gold as a Neural Interface Coating: Effects of Topography, Surface Chemistry, and Feature Size. ACS Applied Materials and Interfaces 7:7093 (2015).

24.   Chapman, C. A. R., Wang, L., Chen, H., Garrison, J., Lein, P. J. & Seker, E. Nanoporous Gold Biointerfaces: Modifying Nanostructure to Control Neural Cell Coverage and Enhance Electrophysiological Recording Performance. Advanced Functional Materials 27:1604631 (2017).

25.   Hampe, A., Li, Z., Sethi, S., Lein, P. & Seker, E. A Microfluidic Platform to Study Astrocyte Adhesion on Nanoporous Gold Thin Films. Nanomaterials 8:452 (2018).

26.   Chapman, C. A., Daggumati, P., Gott, S. C., Rao, M. P. & Seker, E. Substrate topography guides pore morphology evolution in nanoporous gold thin films. Scripta Materialia 110:33 (2016).

27.   Chapman, C. A., Wang, L., Biener, J., Seker, E., Biener, M. M. & Matthews, M. J. Engineering on-chip nanoporous gold material libraries via precision photothermal treatment. Nanoscale 8:785 (2016).

28.   Dorofeeva, T. S., Matharu, Z., Daggumati, P. & Seker, E. Electrochemically Triggered Pore Expansion in Nanoporous Gold Thin Films. The Journal of Physical Chemistry C 120:4080 (2016).

29.   Dorofeeva, T. S. & Seker, E. In Situ Electrical Modulation and Monitoring of Nanoporous Gold Morphology. Nanoscale 8:19551 (2016).

30.   Goshi, N., Girardi, G., da Costa Souza, F., Gardner, A., Lein, P. J. & Seker, E. Influence of microchannel geometry on device performance and electrophysiological recording fidelity during long-term studies of connected neural populations. Lab on a Chip 22:3961 (2022).

31.   Goshi, N., Kim, H. & Seker, E. Primary Cortical Cell Tri-Culture-Based Screening of Neuroinflammatory Response in Toll-like Receptor Activation. Biomedicines 10:2122 (2022).

32.   Goshi, N., Morgan, R. K., Lein, P. J. & Seker, E. A primary neural cell culture model to study neuron, astrocyte, and microglia interactions in neuroinflammation. Journal of Neuroinflammation 17:1 (2020).