Continuous detection of glucose and insulin in live animals

Abstract

Real-time biosensors that can continuously measure circulating biomolecules in vivo would provide valuable insights into a patients’ health status and their response to therapeutics even when there is considerable variability in pharmacokinetics and pharmacodynamics across patient populations. Unfortunately, current real-time biosensors are limited to a handful of analytes (e.g. glucose and blood oxygen) and are limited in sensitivity (high nanomolar). In this work, we describe a general approach for continuously and simultaneously measuring multiple analytes with picomolar sensitivity and sub-second temporal resolution. As exemplars, we report the simultaneous detection of glucose and insulin at picomolar concentrations in live diabetic rats. Using our system, we demonstrate the capacity to resolve inter-individual differences in the pharmacokinetic responses to insulin and discriminate profiles from different insulin formulations at a high temporal resolution. Critically, our approach is general and could be readily modified to continuously and simultaneously measure other circulating analytes in vivo by swapping the affinity reagents, thus making it a versatile tool for biomedical research.

2‐Aminopurine Fluorescence Spectroscopy for Probing a Glucose Binding Aptamer

“…Most previously reported small molecular binding aptamers have much higher affinities (high nM to high μM being most common), [9,14,15] and this glucose aptamer posed challenges for studying its binding [16] . So far, all the fluorescence‐based assays using this aptamer relied on the strand displacement reaction, in which a quencher‐labeled complementary oligonucleotide was required [17,18] . Such a system makes it difficult to study the effect of ionic strength and temperature, since DNA hybridization and melting are also affected by these factors.…”

Simple manual roller pump-driven valve-free microfluidic solution exchange system for urgent bioassay

“…Furthermore, the soft tube assists in fluidic pulsation absorption. 19 The MRP also carries those features in its operation. As a consequence, MRP delivered a smooth pumping experience while exchanging solutions in the reaction chamber.…”

“…Moreover, comparatively wide mFCs and high pressure are required to eliminate uidic resistance. 18,19 Otherwise, valves, such as pneumatic or check valves, are formed in mFCs to control solution delivery. 13,16,17,[19][20][21] To simplify pressure-driven pumping, approaches such as by a nger, 22,23 screw, 24 or chemicals 25 have been reported, eliminating off-chip control for pumping.…”

“…18,19 Otherwise, valves, such as pneumatic or check valves, are formed in mFCs to control solution delivery. 13,16,17,[19][20][21] To simplify pressure-driven pumping, approaches such as by a nger, 22,23 screw, 24 or chemicals 25 have been reported, eliminating off-chip control for pumping. However, they involve extra fabrication steps and additional cost of a thin layer PDMS membrane, rotary electric motor, and chemical modication in the pump unit.…”

A sample-to-answer electrochemical biosensor system for biomarker detection

“…For example, Poudineh et al reported a real-time ELISA which employed deterministic lateral displacement (DLD) sorting to isolate target glucose and insulin analytes. 39 This DLD technique and other microfluidic structure-based approaches have shown promise in filtering blood cells and detecting target biomarkers. However, they can be challenging to implement as they can need to be optimized for purpose and add complexity to device.…”