Steven A. Soper
- Foundation Distinguished Professor
1567 Irving Hill Rd
Lawrence, KS 66045
The major focus of our group is to generate new tools for discovery and medical diagnostics through the analysis of biological macromolecules including DNAs, RNAs and proteins. These tools cover a diverse range of activities, such as the generation of new reagents, novel assays and methodologies, and hardware innovations across various length scales (millimeter to nanometer). What is particularly compelling with our major research goal is that these tools are being integrated into operating systems that can be used for a variety of applications, such as the diagnosis and prognosis of many forms of cancers, stroke and infectious diseases. In order to build systems specifically designed for macro-molecular analyses, our research spans many sub-areas, such as polymer-based micro- and nanomachining, fluorescent probe development, construction of ultrasensitive detection apparati and nano-biology (performing molecular biological reactions in ultra-small volumes). In addition, we are currently working with collaborators in several areas, such as mechanical engineering, molecular biology, surface science, materials, organic chemistry and mass spectrometry. Provided below is a short description of a few of our many projects. To facilitate these multi-disciplinary efforts, our group is part of the Center for BioModular Multi-Scale Systems, which is a multi-institutional research center with access to state-of-the-art equipment and expertise in many disciplines in the sciences and engineering as well.
In the area of reagent development, we have been working on the generation of new instruments that utilize fluorescence-based single-molecule detection. Because the ability to detect single fluorescent molecules depends on low levels of background and fluorescent reporters with high extinction coefficients, quantum yields and favorable photochemical stability, we have synthesized new water-soluble metal phthalocyanines that absorb and emit radiation in the infrared region of the electromagnetic spectrum. Studies are being pursued to understand the photophysical behavior of these metal phthalocyanines, such as why the fluorescent properties of these dyes are highly dependent on the identity of the metal center. The phthalocyanines are being used for labeling oligonucleotides employed to recognize unique reporter sequences within nucleic acid biomarkers to transduce the presence of these markers in real clinical samples.
Novel assays are being developed to facilitate the near real-time reporting of biomarkers unique to a particular disease type. For example, one of our projects is focused on designing and building a Point-of-Care molecular diagnostic test for stroke, which is currently unavailable. We are using fluorescence single-molecule detection to determine the presence of certain messenger RNAs in whole blood that are highly expressed when a patient experiences brain tissue damage. Following isolation of the total RNA from a particular class of cells found in whole blood, the messenger RNAs are subjected to a ligation-based reaction, which allows the formation of so-called molecular beacons. These molecular beacons contain a pair of fluorescent molecules, such as the phthalocyaines described above, and following their formation, allow the dye-pair to undergo a fluorescence resonance energy transfer (FRET) process that generates a unique color signature only if the target messenger RNA is present. We are also developing new assays for collecting tumor cells from circulation, analyzing point mutations in the DNA of these tumor cells and looking at the membrane protein composition of tumor cells that have been shed into circulation and can spawn metastatic disease.
Finally, our hardware developments are primarily focused on designing, fabricating and evaluating microfluidic and nanofluidic chips for cellular and molecular analyses. While many research groups worldwide are engaged in developing lab-on-a-chip systems for biomedical applications, our approach is unique in that conventional polymers, such as Plexiglas and polycarbonate, are being used as the substrate. We are using a variety of new tools to build the prerequisite chips that consist of fluidic channels, which range in size from 10 nm up to 100 µm in size. These tools include hot embossing, optical lithography, laser machining, focused ion beam milling, electron beam lithography, and an assortment of metrology tools (scanning electron microscopy, atomic force microscopy, scanning profilometry, ATR-FTIR, X-ray photoelectron microscopy, and Raman spectroscopy to name a few). The interesting aspect of these chips is that a plethora of surface modification protocols are undertaken on the polymer chips to allow the attachment of biological entities to their surfaces. For example, UV expose of many polymer surfaces creates a functional scaffold composed of carboxylic acids that can be used to covalently attach recognition elements, such as antibodies, directly to their surfaces. These strategies are being employed to generate systems appropriate for the immuno-selection of circulating tumor cells from whole blood for diagnosing a variety of cancers. We are now employing nanofabrication techniques to generate structures in polymer substrates that have dimensions on the order of 10 nm to allow the identification of single-molecules through their unique transport behavior through these nano-confined environments.
- Development of micro-/nanofabricated biochemical analysis systems for clinical diagnostic applications including the analysis of circulating tumor cells and cell free DNA
- Novel fabrication methods for personalized medicine
- Single-molecule fluorescence
The teaching mission of a professor at a major research institution takes on many forms, such as instruction in a formal class setting and mentorship of future professionals (graduate/undergraduate students and post-doctoral associates). While both of these activities are equally important, I have devoted a large amount of my time toward graduate student mentorship as evidenced by the large research group I have sustained over a number of years (39 professional degrees granted). While I realize the importance of undergraduate training, both in the classroom and the research lab, I view graduate mentorship as a unique undertaking for a research professor. I have adopted a strategy to assist in the training of these students for competitively pursuing professional opportunities, whether in the private sector or academia, using a collaborative and multidisciplinary approach. My research group is organized into several teams, with each team focused on a particular project. For all of my projects, students are developing a particular component for the target application, with each student required to heavily interact and become familiar with activities of other members of the team. What is intriguing about this organizational structure is that they are not just interacting with their own research group members, but with students working in diverse disciplines whom are also integral parts of these teams.
To assist in forming effective collaborative efforts amongst students in a particular project team, we hold weekly team meetings. This has been an effective method for students to understand how their work fits into a large project and also, to learn how to interact with others in different disciplines and how to be a team player in multidisciplinary efforts. My feeling is that these experiences prepare them well for their post-graduate work. In addition, I have found that the students become more independent and seek out assistance not only from myself, but their peers and other professors. The post-doctoral associates I support are intimately involved in this activity as well. They typically organize these meetings and select the agenda with input from other team members. This creates an atmosphere of the team members “owning” the project and therefore, become more responsible towards its completion.
Recently, I have become innately aware of the importance of global research as well through my appointment as a World Class Scholar and adjunct professor in South Korea at Ulsan National Institutes of Science and Technology, UNIST. As a result, I have provided to my students unique opportunities to go abroad for sustained periods of time to carry out research. For example, as part of my appointment at UNIST, I have had my graduate students participating in research programs there. In addition, several of my students have received fellowships from NSF to participate in summer research in Korea. This has been a reciprocal arrangement, with students from Korea visiting my laboratories in the US. For example, in the summer of 2012, 3 South Korean students were in my lab and a professor as well.
I have also been involved in undergraduate research and not just through summer research programs, such as REU programs. Over my years at LSU and UNC, I have had many undergraduates whom have joined my research group as freshmen and have stayed within the group during their entire tenure at LSU (new ones at UNC have just started). Three of these students have/are participated in graduate programs in Chemistry (Christie Sayes, Rice University; Sarah Romero, Delaware University and Jason Brabham, Texas A&M University). These undergraduate students are integrated into the research teams outlined above and actively participate in team meetings and have the opportunity to publish peer-reviewed papers and present their work at national/international meetings.
In formal class settings, I have been involved with 11 different courses while at LSU and one at UNC (Biofluid Mechanics) both at the graduate and undergraduate levels. Due to the number of different courses that I have been associated with, a large amount of effort was devoted to developing class notes and general restructuring of the course content. For example, CHEM 2001, the LSU sophomore-level quantitative analysis course, was a new course that was initiated in the fall of 1992. I assisted in developing the curriculum for this course and selecting the textbook. In the spring of 1994, a comprehensive separations class was formulated for graduate-level students. This course offers a complete overview of analytical chromatographic techniques and covers fundamental concepts, gas chromatography, liquid chromatography and specialty areas such as capillary electrophoresis, affinity chromatography and chiral separations. Again, I was intimately involved in developing the content for this course and I am still teaching this course on a regular basis. The new Biofluid Mechanics course at UNC was formulated by myself in the fall of 2012 and was retaught in the fall of 2013.
I have also been engaged in teaching in South Korea as well as part of my duties as a World Class University professor. For two semesters, I taught a class in Bioanalysis and did so from a biology, chemistry and engineering perspective. This was a necessity given that my appointment in Korea was in the Department of Nanobioscience and Chemical Engineering. In the spring of 2013, I taught an undergraduate class (66 students) focused on Biofluid Mechanics and a graduate class in Nanotechnology.
I have also initiated some Professional Development workshops on writing resumes, giving formal presentations and how to participate in an effective interview. I have prepared lectures in each of these areas and have continued to give these lectures at various times over the last 8 years. For example, I gave a formal seminar to the Department of Biomedical Engineering and the Department of Chemistry in 2013 on giving memorable technical presentations. I have also given professional development seminars at LSU, Ulsan National Institute of Science & Technology in Korea and UNC as well.
Another passion I have generated is in the area of entrepreneurship and instructing students on the process of submitting disclosures, writing patents and forming startup companies. I hold informal lectures on the IP process and balancing academic with commercialization ventures. I also discuss with students writing business plans and how to give talks to potential investors as well.
During my first few years at LSU, my teaching duties were specifically oriented toward revamping much of the analytical laboratory courses, which had not experienced a change in over 15 years. My efforts were primarily directed toward both the quantitative analysis course (sophomore-level) and the senior instrumental analysis laboratory. In fact, most of my contributions to the LSU teaching program came from the restructuring of these laboratories. Not only did I design and troubleshoot new laboratories, but diligently sought out new instruments for these teaching laboratories in order to expose students to state-of-the-art analysis in analytical chemistry. Many times this meant going to local industry to secure appropriate equipment that could easily be assimilated into the laboratory.
My ratings in various classes have been consistently higher than the College and Department instructor average. My philosophy for upper level graduate courses is to present the student with a large amount of information due to the expected maturity level of the student and the extensive experience the student should have at this level of his/her career in education. I have also been diligently engaging these students in giving formal presentations by doing in-class talks on selected topical areas.
Selected Publications —
Freed, I.M., Kasi, A., Fateru, O., Hu, M., Gonzales, P., Weatherington, N., Pathak, H., Hyter, S., Sun, W., Al-Rajabi, R., Baranda, J., Hupert, M.L., Chalise, P., Godwin, A.K., Witek, M.A., and Soper, S.A. Circulating Tumor Cell Subpopulations Predict Treatment Outcome in Pancreatic Ductal Adenocarcinoma (PDAC) Patients. Cells 2023, 12(18), 2266. https://doi.org/10.3390/cells12182266
Witek, M.A., Soper, S.A., and Godwin, A.K. Changing the Paradigm in Prognostic Breast Cancer Testing Based on Extracellular Vesicles. RRJ Biol. 2023; 11:009. DOI: 10.4172/2322-0066.11.2.009
Vaidyanathan, S., Wijerathne, H., Gamage, S.S.T., Shiri, F., Zhao, Z., Choi, J., Park, S., Witek, M.A., McKinney, C., Verber, M., Hall, A.R., Childers, K., McNickle, T., Mog, S., Yeh, E., Godwin, A.K., and Soper, S.A. High Sensitivity Extended Nano-Coulter Counter for Detection of Viral Particles and Extracellular Vesicles. Anal. Chem. 2023, 95, 9892-9900. DOI: 10.1021/acs.analchem.3c00855
Hu, M., Brown, V., Jackson, J.M., Wijerathne, H., Pathak, H., Koestler, D.C., Nissen, E., Hupert, M.L., Muller, R., Godwin, A.K., Witek, M.A., and Soper, S.A. Assessing Breast Cancer Molecular Subtypes Using Extracellular Vesicles’ mRNA. Anal. Chem. 2023,95, 19, 7665-7675. DOI: 10.1021/acs.analchem.3c00624
Eades, J.; Audiffred, J.F.; Fincher, M.; Choi, J.-W.; Soper, S.A.; Monroe, W.T. A Simple Micromilled Microfluidic Impedance Cytometer with Vertical Parallel Electrodes for Cell Viability Analysis. Micromachines 2023, 14(2), 283. https://doi.org/10.3390/mi14020283
Jia, Z., Choi, J., Lee, S., Soper, S.A., and Park, S. Modifying surface charge density of thermoplastic nanofluidic biosensors by multivalent cations within the slip plane of the electric double layer. Colloids and Surfaces A: Physiochemical and Engineering Aspects, 2022, 648, 129147. https://doi.org/10.1016/j.colsurfa.2022.129147
Gamage, S.S.T., Pahattuge, T. N., Wijerathne, H., Childers, K., Vaidyanathan, S., Athapattu, U.S., Zhang, L., Zhao, Z., Hupert, M.L., Muller, R.M., Muller-Cohn, J., Dickerson, J., Dufek, D., Geisbrecht, B.V., Pathak, H., Pessetto, Z., Gan, G.N., Choi, J., Park, S., Godwin, A. K., Witek, M.A., Soper, S.A., Microfluidic affinity selection of active SARS-CoV-2 virus particles. Sci. Adv., 8 (39), eabn9665. DOI: 10.1126/sciadv.abn9665
Rathnayaka, C., Amarasekara, C.A., Akabirov, K., Murphy, M.C., Park, S., Witek, M.A., Soper, S.A., Nanofluidic devices for the separation of biomolecules,
Journal of Chromatography A, Volume 1683, 2022,463539,ISSN 0021-9673, https://doi.org/10.1016/j.chroma.2022.463539.
Zhao, Z., Vaidyanathan, S., Bhanja, P., Gamage, S., Saha, S., McKinney, C., Choi, J., Park, S., Pahattuge, T., Wijerathne, H., Jackson, J.M., Hupert, M.L., Witek, M.A., and Soper, S.A. (2022), In-plane Extended Nano-coulter Counter (XnCC) for the Label-free Electrical Detection of Biological Particles. Electroanalysis. https://doi.org/10.1002/elan.202200091
Choi, J., Jia, Z., Riahipour, R., McKinney, C. J., Amarasekara, C. A., Weerakoon-Ratnayake, K. M., Soper, S. A., Park, S., Label-Free Identification of Single Mononucleotides by Nanoscale Electrophoresis. Small 2021, 17, 2102567. https://doi.org/10.1002/smll.202102567.
Uditha S. Athapattu, Chathurika Rathnayaka, Swarnagowri Vaidyanathan, Sachindra S. T. Gamage, Junseo Choi, Ramin Riahipour, Anishkumar Manoharan, Adam R. Hall, Sunggook Park, and Steven A. Soper, "Tailoring Thermoplastic In-Plane Nanopore Size by Thermal Fusion Bonding for the Analysis of Single Molecules," ACS Sensors2021 6 (8), 3133-3143.
Camila D.M. Campos, Katie Childers, Sachindra S.T. Gamage, Harshani Wijerathne, Zheng Zhao, Steven A. Soper Annual Review of Analytical Chemistry 2021 14:1, 207-229, "Analytical Technologies for Liquid Biopsy of Subcellular Materials," Annual Review of Analytical Chemistry2021 14:1, 207-229.
X. Zhao, D. S. . -W. Park, S. A. Soper and M. C. Murphy, "Microfluidic Gasketless Interconnects Sealed by Superhydrophobic Surfaces," in Journal of Microelectromechanical Systems, vol. 29, no. 5, pp. 894-899, Oct. 2020, doi: 10.1109/JMEMS.2020.3000325.
Awards & Honors —
R & D 100 Award, Single Molecule Detection Device
Shannon Award, National Institutes of Health (National Human Genome Research Institute)
Whitaker Foundation Award, Whitaker Bioengineering Research Foundation
Outstanding Researcher, College of Basic Sciences, Louisiana State University
Charles E. Coates Award for Outstanding Contributions to Chemical/Engineering Research in Louisiana, Louisiana State University
William L. & Patricia Senn, Jr. Professor of Chemistry
2002 - 2009
Distinguished Research Master, Louisiana State University (Top Research Award Offered by the University)
Rainmaker - LSU Top 100 Researcher, Louisiana State University
Rainmaker - LSU Top 100 Researcher, Louisiana State University
William H. Pryor Professor of Chemistry, Louisiana State University
Fellow, Society for Applied Spectroscopy
Fellow, Royal Society of Chemistry
Fellow, American Association for the Advancement of Science
American Chemical Society; Advances in Chemical Instrumentation
Assistant Professor, Louisiana State University
Associate Professor, Louisiana State University
Professor, Louisiana State University
2000 - 2011
Associate Editor of the Americas for Analyst
2010 - present
Professor Biomedical Engineering, UNC/NCSU
Professor Chemistry, University of North Carolina, Chapel Hill
Distinguished Professor Chemistry, University of Kansas, Lawrence