The surface density gradient of grafted poly(ethylene glycol): Preparation, characterization and protein adsorption

Lin, Yung‐Sen; Hlady, Vladimir; Gölander, C.-G.

doi:10.1016/0927-7765(93)01114-7

Cited by 89 publications

(104 citation statements)

References 32 publications

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“…We verified our hypothesis by Minimizing inflammation is also an important issue for transdermal, long-term in vivo CGM because inflammation causes (i) interference with transdermal fluorescence transmission (see Fig. S6), (ii) physiological condition changes, and (iii) sensor isolation resulting from fibrous capsules (18)(19)(20). To suppress the inflammatory reaction, the sensors must be designed such that they minimize tissue injury, promote tissue recovery, and limit fibrous capsule formation.…”

Section: Discussionmentioning

confidence: 64%

Long-term in vivo glucose monitoring using fluorescent hydrogel fibers

Heo

Shibata

Okitsu

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

284

227

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The use of fluorescence-based sensors holds great promise for continuous glucose monitoring (CGM) in vivo, allowing wireless transdermal transmission and long-lasting functionality in vivo. The ability to monitor glucose concentrations in vivo over the long term enables the sensors to be implanted and replaced less often, thereby bringing CGM closer to practical implementation. However, the full potential of long-term in vivo glucose monitoring has yet to be realized because current fluorescence-based sensors cannot remain at an implantation site and respond to blood glucose concentrations over an extended period. Here, we present a long-term in vivo glucose monitoring method using glucose-responsive fluorescent hydrogel fibers. We fabricated glucose-responsive fluorescent hydrogels in a fibrous structure because this structure enables the sensors to remain at the implantation site for a long period. Moreover, these fibers allow easy control of the amount of fluorescent sensors implanted, simply by cutting the fibers to the desired length, and facilitate sensor removal from the implantation site after use. We found that the polyethylene glycol (PEG)-bonded polyacrylamide (PAM) hydrogel fibers reduced inflammation compared with PAM hydrogel fibers, transdermally glowed, and continuously responded to blood glucose concentration changes for up to 140 days, showing their potential application for long-term in vivo continuous glucose monitoring.glucose-responsive fluorescence | long-lasting implantable sensor | biocompatible interface | implantable glucose sensor | diabetes mellitus I n vivo glucose monitoring allows continuous glucose monitoring (CGM) and facilitates intensive control of blood glucose concentrations in diabetic patients. Long-lasting implantable sensors can reduce the frequency of implantation and replacement, resulting in long-term in vivo glucose monitoring with less effort by patients and less tissue damage. For decades, implantable sensors for long-term use have been developed using enzyme electrodes. However, these methods have several drawbacks for long-term use because these enzyme based sensors are insufficiently stable in vivo (1), they are poorly accurate in low glucose concentrations (2), and their activity is oxygen-dependent (3). In contrast, glucose-responsive fluorescence is a promising approach that maintains long-lasting functionality in vivo due to its enzyme-free and reversible reaction (4-9). We recently developed fluorescent hydrogel microbeads that are transdermally detectable, injectable, minimally invasive, and biocompatible (10). To bring this technology closer to long-term application, the fluorescent hydrogel sensors need to remain at the implantation site for a long period (over 3 mo) and be easily removable after use; despite their great potential for continuous glucose monitoring, the microbeads were not suitable for long-term monitoring in vivo because they dispersed from the implantation site and were difficult to remove. In addition, the biointerface of the fluoresce...

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Section: Discussionmentioning

confidence: 64%

Long-term in vivo glucose monitoring using fluorescent hydrogel fibers

Heo

Shibata

Okitsu

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

284

227

View full text Add to dashboard Cite

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“…Based on reported PEG density (1.1-1.2 g/cm 3 ), 44,56 and the molecular weight of the macromolecules (MW PEG = 2 kDa), the surface concentration was calculated to be 3.5 (±0.6) PEG molecules per nm 2 . For previously reported procedures for grafting PEG chains to surfaces of substrates such as silica or gold, the packing density of PEGs (MW larger than about 0.5 kDa) was less than one molecule per nm 2 .…”

Section: Ellipsometrymentioning

confidence: 99%

Surface-Bound Proteins with Preserved Functionality

et al. 2009

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Abstract-Biocompatibility of materials strongly depends on their surface properties. Therefore, surface derivatization in a controllable manner provides means for achieving interfaces essential for a broad range of chemical, biological, and medical applications. Bioactive interfaces, while manifesting the activity for which they are designed, should suppress all nonspecific interaction between the supporting substrates and the surrounding media. This article describes a procedure for chemical derivatization of glass and silicon surfaces with polyethylene glycol (PEG) layers covalently functionalized with proteins. While the proteins introduce the functionality to the surfaces, the PEGs provide resistance against nonspecific interactions. For formation of aldehyde-functionalized surfaces, we coated the substrates with acetals (i.e., protected aldehydes). To avoid deterioration of the surfaces, we did not use strong mineral acids for the deprotection of the aldehydes. Instead, we used a relatively weak Lewis acid for conversion of the acetals into aldehydes. Introduction of a,x-bifunctional polymers into the PEG layers, bound to the aldehydes, allowed us to covalently attach green fluorescent protein and bovine carbonic anhydrase to the surfaces. Spectroscopic studies indicated that the surface-bound proteins preserve their functionalities. The surface concentrations of the proteins, however, did not manifest linear proportionality to the molar fractions of the bifunctional PEGs used for the coatings. This finding suggests that surface-loading ratios cannot be directly predicted from the compositions of the solutions of competing reagents used for chemical derivatization.

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“…Since their report, many reports on PEG-chain-tethered surfaces have been published. [9][10][11][12] We have begun to investigate the performance of PEG tethered chains in producing anti-biofouling effects using our original heterobifunctional PEG. From our investigation, both chain length and density of PEG are important factors in improving the non-biofouling character of surfaces.…”

mentioning

confidence: 99%

Construction of a densely poly(ethylene glycol)-chain-tethered surface and its performance

Nagasaki

2011

Polym J

116

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Non-biofouling surfaces constitute one of the most important subjects in sensitively and selectively detecting biomolecular events. Poly(ethylene glycol) (PEG) chains tethered on substrate surfaces are well known to reduce non-biofouling characteristics. Protein adsorption onto a PEG-chain-tethered surface is strongly influenced by the density of the PEG chain and is almost completely suppressed by the successive treatment of longer PEG chains (5 kDa) followed by the treatment of PEG (2 kDa; mixed-PEG-chain-tethered surface) because of a significant increase in PEG chain density. To modify versatile substrate surface, PEG possessing pentaethylenehexamine at one end (N6-PEG) was prepared via a reductive amination reaction of aldehyde-ended PEG with pentaethylenehexamine. Using N6-PEG, antibody/PEG co-immobilization was conducted on a substrate possessing active ester groups. After the antibody was immobilized on the surface, PEG tethered chains were constructed surrounding the immobilized antibody. It is interesting to note that the PEG-chain-tethered functions not only as a non-fouling agent but also improves immune response. The hybrid surface was also applied to oligo DNA immobilization. The oligo DNA/PEG hybrid surface improved hybridization, retaining its non-fouling ability. Densely packed PEG tethered chains surrounding antibodies and/or oligo DNA improved their orientation on the surface. Thus, this material is promising as a high-performance biointerface for versatile applications. Keywords: antibody; biosensing; DNA; end-functionalized poly(ethylene glycol); enzyme-linked immunosorbent assay; hybrid biointerface; soft interface INTRODUCTION Specific biorecognition on substrate surfaces has long been utilized in many applications such as biosensing, 1 immunodiagnostics, 2 enzyme immunoassay, 3 western blotting 4 and protein microarrays. 5 Important factors for the improvement in specific biorecognition on surfaces are the suppression of nonspecific biofouling and the suitable orientation of immobilized biomolecules. The former decreases nonspecific noise and the background level, and the latter increases the specific recognition level. To improve the non-biofouling character of surfaces, numerous efforts have been undertaken. In general, natural polymers such as albumin, casein and dextran have been used for blocking on substrate surfaces. 6 These treatments work well and suppress protein biofouling extensively. If extremely high performance is required, however, these blocking treatments are not enough. In addition, natural products, especially those derived from animals, may have undesired contents such as bacteria and viruses, which may affect the user. 7 Under these circumstances, synthetic polymers have been recently suggested as suitable surface blocking agents. Numerous types of water-soluble polymers, such as poly(acrylamide), poly(vinyl alcohol), poly(vinyl pyrrolidone) and poly(ethylene glycol) (PEG), have been investigated so far. Recently, new types of synthetic polymers such as poly(methoxy ...

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The surface density gradient of grafted poly(ethylene glycol): Preparation, characterization and protein adsorption

Cited by 89 publications

References 32 publications

Long-term in vivo glucose monitoring using fluorescent hydrogel fibers

Long-term in vivo glucose monitoring using fluorescent hydrogel fibers

Surface-Bound Proteins with Preserved Functionality

Construction of a densely poly(ethylene glycol)-chain-tethered surface and its performance

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