Lab-on-a-tube for in situ ocular bioassays: continuous glucometry in tears

Abstract

 

Purpose

 

Non-invasive monitoring is an expanding frontier for biomedical assays. Integrated Bio-Micro-Electro-Mechanical-Systems (BioMEMS) have enabled miniaturization of clinical assays into integrated testing platforms for the point-of-care (POC). BioMEMS have the ability to push the envelope on blood tests at the POC. Tear film glucometry and the methods for tear sampling may obviate the need for painful finger sticks, and facilitate tighter blood glucose control in diabetic patients. We propose to develop a lab-on-a-tube (LOT) platform for continuously monitoring tear dynamics.

 

Methods

 

Platinum nanoparticle-coated gold (Pt NP, working and counter), and Iridium oxide (reference) microelectrodes were fabricated on 7.5 μm thick polyimide film. The Pt NP electrodes were coated with Poly(ο-phenylenediamine) (PPD) to eliminate interference. GOD-chitosan-glutaraldehyde solution was deposited for a favorable glucose oxidase (GOD) microenvironment. The flexible LOT may have sensors on either inner or outer surface. Artificial tear solution was prepared with 130 mM sodium chloride, 10 mM dibasic sodium phosphate and 10 mM monobasic sodium phosphate, lysozyme 1.9 mg/mL, albumin 0.2 mg/mL and mucin 0.15 mg/mL in deionized water, at pH 7.4. Electrochemical glucose detection was performed with a PalmSens® at 37°C.

 

Results

 

Figure 1 shows the LOT. Incremental increases in glucose concentration were measured in artificial tear solution (Fig.2). The sensor demonstrated a linear response range, sensitivity and detection limits of 0.01 - 2 mM, 35.8 nA/mM and 0.01 mM, respectively. The glucose sensor sustained sensitivity for 7 days of continuous activity with 95% original response retention.

 

Conclusions

 

The LOT demonstrates high sensitivity for glucose concentrations characteristic of the tear film. With our previous data demonstrating stability of glucose sensors in artificial CSF over the period of months, our early platform for tear glucometry may provide a means for long term ocular glucometry for months at a time. Ultimately, this tube architecture could find utility for glucometry in smart punctal stents or glaucoma drainage implants.

 

 

Figure 1: Photographs of the microfabricated LOT. WE = working electrode, CE = Counter electrode, RE = reference electrode.

 

 

Figure 2: Current output from glucose sensor exposed to incrementally increased glucose concentration in artificial tear solution.

 

Keywords: 498 diabetes • 607 nanotechnology