An Inexpensive Point-of-Care Sensor for Monitoring Blood Acetaldehyde Concentration with Application to Alcohol Metabolism and Cancer Risk

Elevated blood acetaldehyde concentrations are damaging to body organs and increase cancer risk. Smoking substantially increases blood acetaldehyde levels, as does alcohol consumption by individuals lacking the enzyme acetaldehyde dehydrogenase (ALDH2). Normally consumed ethanol is first converted to acetaldehyde, which is then converted to acetic acid by ALDH2. This is fortunate because acetaldehyde is far more toxic than ethanol or acetic acid. However, many individuals lack ALDH2, including 25-40 % of the Asian population. For these individuals, smoking or alcohol consumption is very risky. Currently systemic acetaldehyde levels are estimated via breath measurements. However, breath aldehyde concentration values have less clinical significance than blood concentration values. In addition, acetaldehyde levels vary with body location and this cannot be detected using breath measurements. It is currently possible to measure blood aldehyde concentrations but this involves sending samples to analytical labs that use expensive equipment. These difficulties could be avoided with the point-of-care sensor proposed here consisting of a smart pH-responsive hydrogel containing immobilized ALDH2. When this hydrogel absorbs a blood sample, ALDH2 will convert acetaldehyde to acetic acid, thereby lowering the pH and causing swelling of the pH-responsive hydrogel. Inexpensive methods are available for transducing hydrogel swelling changes into electrical signals.

Current Status

2024-01-09
An Inexpensive Point-of-Care Sensor for Monitoring Blood Acetaldehyde Concentration with Application to Alcohol Metabolism and Cancer Risk
Funded in 2023 for $30,000
Jules Magda+, Lars Laurentius*, Kai Kuck#, Jonathan Grubb+, Hannah Nordhoff&
+Chemical Engineering; *Electrical and Computer Engineering; #Anesthesiology; &Chemistry

When alcohol is consumed, this may lead to an accumulation of acetaldehyde in the body that poses health risks, especially for groups like 25-40% of East Asians and Native Americans who have a genetic sensitivity to it. Current methods to measure its levels are costly and slow. We aim to develop a monitoring system to give immediate feedback on acetaldehyde exposure, especially for at-risk individuals. This would also benefit studies assessing acetaldehyde's broader health impacts. The proposed technology uses a smart pH-responsive hydrogel with ALDH2 enzymes to convert increases in acetaldehyde concentration into acetic acid concentration increases, decreases in pH, hydrogel swelling responses, and resulting electrical signals. Our goals are to: (1) identify acetaldehyde levels from smoking or alcohol, (2) assess the pH drop in an ALDH2-containing hydrogel that can be implanted in the body, (3) optimize the hydrogel's composition to monitor acetaldehyde levels, and (4) base an NIH R21 proposal on these findings.

CURRENT STATUS AND NEXT STEPS
Plasma acetaldehyde concentrations after alcohol consumption are on the order of 10-20 ug/dL following consumption by an adult of a standard drink of alcohol (14g of alcohol, e.g., a glass of wine). In individuals with the ALDH2*1/*2 mutation, that concentration is 600% (!) higher.1
A number of different smart hydrogels were made and exposed to a range of pH (acidity) levels. Figure 1 shows their swelling response. Acetic acid, the end product of acetaldehyde's enzyme-mediated metabolism, produces a small pH change, e.g., from pH 7.2 to 7.3, but similarly produces a hydrogel swelling response as large as 24%. This amount of swelling response can easily be transduced into an electric signal appropriate for a point-of-care sensor. Currently, the swelling response is too slow for real-world point-of-care sensor applications, requiring a redesign in the hydrogel's thickness down from 3,200 um. This is under way. We have not been able, yet, to demonstrate the pH change that results from ALDH mediating the reaction from acetaldehyde to acetic acid.
In next steps, we are redesigning the hydrogel's form factor, aiming to design a bending strip with a very thin layer of hydrogel on one side. The small dimensions should decrease the hydrogel's response time. We will also combine the ALDH enzyme with NAD+, an enzyme co-factor, which will speed up the catalysis of acetaldehyde into acetic acid.

COLLABORATORS
Collaborators on this project include Jules Magda (Chemical Engineering faculty, Project Owner), Lars Laurentius (Electrical Engineering faculty, expert in instrumentation and chemical analytics), Kai Kuck (Anesthesiology and Biomedical Engineering faculty, expert in patient monitoring), Jonathan Grubb (PhD candidate, Chemical Engineering), and Hannah Nordhoff (Undergraduate Student, Chemistry).
Hanna Nordhoff was able to secure UROP funding for her work on this project.

1Kim et al. Biol Psychiatr. 2010 ;67(9)