Glucose biosensors based on Michael addition crosslinked poly(ethylene glycol) hydrogels with chemo-optical sensing microdomains. 2023

Tyrell J Williams, and Ananthakrishnan S Jeevarathinam, and Faraz Jivan, and Victoria Baldock, and Paul Kim, and Michael J McShane, and Daniel L Alge
Department of Biomedical Engineering, Texas A&M University, College Station, Texas, USA. dalge@tamu.edu.

Continuous glucose monitoring (CGM) devices have the potential to lead to better disease management and improved outcomes in patients with diabetes. Chemo-optical glucose sensors offer a promising, accurate, long-term alternative to the current CGMs that require frequent calibration and replacement. Recently, we have proposed glucose sensor designs using phosphorescence lifetime-based measurement of chemo-optical glucose sensing microdomains embedded within alginate hydrogels. Due to the poor long-term stability of calcium-crosslinked alginate, we propose poly(ethylene glycol) (PEG) hydrogels synthesized via thiol-Michael addition chemistry as an alternative hydrogel carrier. The objective of this study was to evaluate the suitability of Michael addition crosslinked PEG hydrogels compared to calcium crosslinked alginate hydrogels for encapsulating glucose-sensing microdomains. PEG hydrogels crosslinked via thiol-vinyl sulfone addition achieved gelation in under 5 minutes, resulting in an even distribution of sensing microdomains. The shear storage modulus of the PEG hydrogels was tunable from 2.2 ± 0.1 kPa to 9.5 ± 1.8 kPa, which was comparable to the alginate hydrogels (10.5 ± 0.8 kPa), and the inclusion of microdomains did not significantly impact stiffness. The high water content of PEG hydrogels resulted in high glucose permeability that closely corresponded to the glucose permeability of alginate (D = 0.09 and 0.12 cm2 s-1, respectively; p = 0.47), but the PEG hydrogels exhibited superior stability. Both PEG and alginate-embedded sensors exhibited a sensing range up to ∼200 mg dL-1 glucose. The lower limits of detection (LOD) for PEG and alginate-based glucose sensors were 19.8 and 20.6 mg dL-1 with a difference of just 4.2% variation. The small difference between PEG and alginate embedded sensors indicates that their sensing properties are primarily determined by the glucose sensing microdomains rather than the hydrogel matrix. Overall, the results of this study indicate that Michael addition-crosslinked PEG hydrogels are a promising platform for encapsulation of chemo-optical glucose sensing microdomains.

UI MeSH Term Description Entries
D011092 Polyethylene Glycols Polymers of ETHYLENE OXIDE and water, and their ethers. They vary in consistency from liquid to solid depending on the molecular weight indicated by a number following the name. They are used as SURFACTANTS, dispersing agents, solvents, ointment and suppository bases, vehicles, and tablet excipients. Some specific groups are NONOXYNOLS, OCTOXYNOLS, and POLOXAMERS. Macrogols,Polyoxyethylenes,Carbowax,Macrogol,Polyethylene Glycol,Polyethylene Oxide,Polyethyleneoxide,Polyglycol,Glycol, Polyethylene,Glycols, Polyethylene,Oxide, Polyethylene,Oxides, Polyethylene,Polyethylene Oxides,Polyethyleneoxides,Polyglycols,Polyoxyethylene
D001786 Blood Glucose Glucose in blood. Blood Sugar,Glucose, Blood,Sugar, Blood
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D005947 Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000464 Alginates Salts and esters of ALGINIC ACID that are used as HYDROGELS; DENTAL IMPRESSION MATERIALS, and as absorbent materials for surgical dressings (BANDAGES, HYDROCOLLOID). They are also used to manufacture MICROSPHERES and NANOPARTICLES for DIAGNOSTIC REAGENT KITS and DRUG DELIVERY SYSTEMS. Alginate,Alginic Acid, Barium Salt,Alginic Acid, Calcium Salt,Alginic Acid, Copper Salt,Alginic Acid, Potassium Salt,Alginic Acid, Sodium Salt,Alloid G,Barium Alginate,Calcium Alginate,Calginat,Copper Alginate,Kalrostat,Kalrostat 2,Kaltostat,Potassium Alginate,Sodium Alginate,Sodium Calcium Alginate,Vocoloid,Xantalgin,poly(Mannuronic Acid), Sodium Salt,Alginate, Barium,Alginate, Calcium,Alginate, Copper,Alginate, Potassium,Alginate, Sodium,Alginate, Sodium Calcium,Calcium Alginate, Sodium
D001672 Biocompatible Materials Synthetic or natural materials, other than DRUGS, that are used to replace or repair any body TISSUES or bodily function. Biomaterials,Bioartificial Materials,Hemocompatible Materials,Bioartificial Material,Biocompatible Material,Biomaterial,Hemocompatible Material,Material, Bioartificial,Material, Biocompatible,Material, Hemocompatible
D013438 Sulfhydryl Compounds Compounds containing the -SH radical. Mercaptan,Mercapto Compounds,Sulfhydryl Compound,Thiol,Thiols,Mercaptans,Compound, Sulfhydryl,Compounds, Mercapto,Compounds, Sulfhydryl
D015190 Blood Glucose Self-Monitoring Self evaluation of whole blood glucose levels outside the clinical laboratory. A digital or battery-operated reflectance meter may be used. It has wide application in controlling unstable insulin-dependent diabetes. Blood Sugar Self-Monitoring,Home Blood Glucose Monitoring,Monitoring, Home Blood Glucose,Self-Monitoring, Blood Glucose,Glucose, Blood, Self Monitoring,Glucose, Blood, Self-Monitoring,Blood Glucose Self Monitoring,Blood Glucose Self-Monitorings,Blood Sugar Self Monitoring,Blood Sugar Self-Monitorings,Glucose Self-Monitoring, Blood,Glucose Self-Monitorings, Blood,Self Monitoring, Blood Glucose,Self-Monitoring, Blood Sugar,Self-Monitorings, Blood Glucose,Self-Monitorings, Blood Sugar,Sugar Self-Monitoring, Blood,Sugar Self-Monitorings, Blood
D015374 Biosensing Techniques Any of a variety of procedures which use biomolecular probes to measure the presence or concentration of biological molecules, biological structures, microorganisms, etc., by translating a biochemical interaction at the probe surface into a quantifiable physical signal. Bioprobes,Biosensors,Electrodes, Enzyme,Biosensing Technics,Bioprobe,Biosensing Technic,Biosensing Technique,Biosensor,Electrode, Enzyme,Enzyme Electrode,Enzyme Electrodes,Technic, Biosensing,Technics, Biosensing,Technique, Biosensing,Techniques, Biosensing

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