Project Title: Ultrafast, Low-Noise Electrochemical Test System for Single Molecule Measurement for Miami Students

Project Lead's Name: Hang Ren

Project Lead's Email: renhang@MiamiOH.edu

Project Lead's Phone: 513-529-0854

Project Lead's Division: CAS

Primary Department: Department of Chemistry and Biochemistry

Other Team Members and their emails:

• Neil Danielson: danielnd@MiamiOH.edu
• Andy Sommer: sommeraj@MiamiOH.edu

List Departments Benefiting or Affected by this proposal:

• Department of Chemistry and Biochemistry
• Department of Chemical, Paper, and Biomedical Engineering

Estimated Number of Under-Graduate students affected per year (should be number who will actually use solution, not just who is it available to): 50

Estimated Number of Graduate students affected per year (should be number who will actually use solution, not just who is it available to): 10

Describe the problem you are attempting to solve and your approach for solving that problem: For more than a century, chemists have investigated chemical reactions involving the number of molecules on the order of 10̂23. One cutting-edge technology in chemistry and especially in analytical and physical chemistry is the ability to experimentally measure the behavior of single molecules. Though many techniques for single molecule measurement have recently been demonstrated in academic research, none of them is directly available to the students at Miami. The statistical behavior of molecules is often underappreciated because of the lack of hands-on experience in single-molecule measurement. A great chance to teach the students in science and engineering statistical analysis and modeling, which is becoming increasingly important skills for academic and industry, is missed.

We proposed to acquire a low-noise, high-bandwidth electrochemical system that can be used to demonstrate the single molecule measurement to the students. The state-of-the-art system will be first introduced as one of the special projects in CHM 375 (Analytical Chemistry) as a pilot project. This course is taken by students not only from chemistry and biochemistry, but also from Chemical and Biomedical Engineering students from the Chemical, Paper and Bioengineering Department (CPB). CHM 375 has an average of 60 undergraduate students per year. The electrochemical system that we proposed to acquire here is robust and is suitable for undergraduate students, while being lower cost compare to other single molecule techniques (e.g. single molecule fluorescence). The experiment can also be implemented in the physical chemistry lab, CHM 456.

The acquisition of the equipment will be forward-looking, making Miami among the first to implement such state-of-the-art technology directly into teaching. Meanwhile, continuing with the long success the chemistry department has for undergraduate and graduate research experience, the equipment will also be available for undergraduate Independent Research Capstone projects and as a lab assignment for graduate students as part of my Electrochemistry course, CHM 460/760. The success of the project will also open future opportunities for implementation in other chemistry courses.

How would you describe the innovation and/or the significance of your project: Single molecular measurement, random nature of molecular behavior is an important concept among many different courses from introductory level to graduate level chemistry (e.g. CHM 141/142 College Chemistry, CHM 144/145 College Chemistry Laboratory, CHM 375 Analytical Chemistry CHM 454/CHM 554. Instrumental Analysis, CHM 451/CHM 551. Physical Chemistry for Chemistry Majors). These courses are not only taken by chemistry and biochemistry students, but also by students across the campus, including Biology, Chemical, Paper and Bioengineering, and Mechanical and Manufacturing Engineering.

The concept of single-molecule measurement while being intuitively simple (analyzing only one molecule is simpler than analyzing many molecules), is often overlooked in undergraduate education because of the unavailability of such measurements to undergraduate students. The proposed project is highly innovative as the success of this project will put Miami among the first across the country to introduce single-molecule experiment into undergraduate classes.

This proposal aims to increase the teaching and research capabilities in the Chemistry and Biochemistry Department and enhance the quality of academic experience of students across the campus in preparation for their professional activity. This is in accordance with the educational mission of the department, the college and the university. A direct result of the project if successful is the great enhancement of Miami students’ unique academic experience on the state-of-the-art technology (compared to many other institutes among the country). Meanwhile, the random behavior of individual molecules and the big data concomitant with single molecule measurement will acquaint the students with valuable skills of statistical and data analytics. These data analytic skills are playing increasingly important roles across many different disciplines in both academic and industry while being generally lacking in students in physical science.

In a typical experiment, protein channels can be inserted into a suspended lipid bilayer, which creates a nanoscale “test tube” that allows only one or a handful of molecules to be contained and measured. The current will change due to the presence and absence of a target molecule (e.g. β-cyclodextran) inside the protein channel, which will generate a change in current on the orders of tens of picoamp (10-12 A!). This small current can be detected by the proposed Ultrafast, Low-Noise Electrochemical Test System. The current signature will contain information about the movement of the single molecule as well as the interaction between the single molecule and the protein, which are often seen as cartoons but not in real experiments (See Figure 1). For example, the duration of a molecule stays inside the nanoscale “test tube” will be random, but will follow certain statistical distributions. This is an important concept in analytical chemistry, physical chemistry and statistics. The current level, as well as the duration of the current each molecule generates, will be analyzed by the students, which will generate statistics for each molecule and many different molecules as a whole.

How will you assess the success of the project: The primary goal of the project is to significantly enhance Miami students’ hands-on experience on the state-of-the-art technology in their chemistry courses and research. One assessment of the project will be shown in training students with the knowledge and skills in single molecule measurement and data analytics. Another assessment of the success of this project will be data collected by the evaluation/survey of the CHM 375 regarding the quality of the lab experience, specifically to the special projects. The third will be the presentations and capstones that make use of the system.

Total Amount Requested: $31,872

Budget Details: Budget Justification

The electrochemical system (Axon 200B-2) with the low noise data acquisition system (DIGIDATA 1550B1) will allow fast and low current measurement, which is the key component in single molecule electrochemistry measurement. The PCalmp 11 software is used to control the instrument and to display and analyze the data, which are used by the students. The consumables will be a protein monomer and lipids, creating a nanoscale “beaker” for observation of a single molecule. The Faraday cage and test cell will be fabricated by Miami University Instrumentation Laboratory, which further reduces the electronic noise and facilitates students’ experiment.

Is this a multi-year request: No

Please address how, if at all, this project impacts any of Miami's BCSAE, 2020, or divisional plans: The availability of the state-of-art instrument will acquaint the students with the cutting-edge technique, prepare the students with versatile skills including big data analytics, which is directly in accord with both BCSAE. The success of the project will further “advance Miami’s reputation for excellence and innovation”, and “promote a vibrant learning and discovery environment that produces extraordinary student and scholarly outcomes”, which are direct goals of BCSAE and Miami University 2020 Plan, respectively.