Transforming the blood glucose meter into a general healthcare meter for in vitro diagnostics in mobile health

Abstract

Recent advances in mobile network and smartphones have provided an enormous opportunity for transforming in vitro diagnostics (IVD) from central labs to home or other points of care (POC). A major challenge to achieving the goal is a long time and high costs associated with developing POC IVD devices in mobile Health (mHealth). Instead of developing a new POC device for every new IVD target, we and others are taking advantage of decades of research, development, engineering and continuous improvement of the blood glucose meter (BGM), including those already integrated with smartphones, and transforming the BGM into a general healthcare meter for POC IVDs of a wide range of biomarkers, therapeutic drugs and other analytical targets. In this review, we summarize methods to transduce and amplify selective binding of targets by antibodies, DNA/RNA aptamers, DNAzyme/ribozymes and protein enzymes into signals such as glucose or NADH that can be measured by commercially available BGM, making it possible to adapt many clinical assays performed in central labs, such as immunoassays, aptamer/DNAzyme assays, molecular diagnostic assays, and enzymatic activity assays onto BGM platform for quantification of non-glucose targets for a wide variety of IVDs in mHealth.

Introduction

Coinciding with the rise of the aging population, the prevalence of chronic diseases and the associated healthcare costs has skyrocketed, making it challenging to improve both the quality and the reach of healthcare to those in need. One promising solution is to shift healthcare from hospitals and centralized laboratories to small clinics in the communities and at home or the point of care (POC). To achieve the goals, enormous effort has been made in the past decade to develop technologies that allow rapid patient-provider communications and more convenient diagnostic tests to use by less trained staffs at a lower cost. These efforts have been empowered by today's computational power, fast and reliable networks, and rich software content, with particular impact on POC in vitro diagnostics and mobile health.

Recent advances in mobile technologies have led to significant advances in personal health monitoring and healthcare delivery. For example, many wearable devices, such as wristbands and smartwatch, have been commercialized to monitor an individual's vital signs, such as blood pressure, heart rate, and body temperature, and behavior like medication adherence and physical movement (mHealth, 2012). In addition, without needing to be physically at the clinic, communications and consultation with healthcare providers as well as health education can be delivered to anyone with a smartphone or tablet. All the information can be transmitted and stored in the cloud for patients and their caregivers to access and monitor their health status. However, these technologies are mostly limited to delivering information about fitness and healthy state of the users using physical parameters and they miss a critical component of performing diagnostic or screening tests, i.e., using biomarkers inside a human body, which are known to be much more informative and accurate. Furthermore, many therapeutic drugs are known to have narrow therapeutic windows and careful monitoring of the drug levels in the patients regularly at home or other places of POC is critical to successful therapy.

To develop mHealth meters to detect and quantify biomarkers and therapeutic drugs inside a human body, such as those in the blood, urine or saliva, it requires much more advanced technology and thus research and development efforts and funding. Currently, the blood glucose meter (BGM) is the only widely used in vitro diagnostic (IVD) device that has been integrated with mHealth application, either as an attachment to a smartphone (iBGSTAR, 2011) or directly integrating cellular capability (Telcare, 2013). With the growing prevalence of diabetes worldwide, it is not surprising that the BGM is at the forefront of IVDs adapting to the mHealth trend. Decades of research and development, engineering, and marketing efforts have made glucose sensing technology more affordable, accurate, portable, easy to use and low cost to manufacture. In addition, BGM technologies are continuously under development to address needs of the growing population of people with diabetes (Hones et al., 2008). Therefore, instead of developing a brand new platform for IVD tests with mobile devices, leveraging the existing BGM platform to quantify other clinical relevant biomarkers can mitigate risk and lower the costs. Guided by this strategy, we and others have recently transformed unmodified commercially available BGM into a general healthcare meter for IVD in mHealth (Xiang and Lu, 2011, Xiang and Lu, 2012a, Xiang and Lu, 2012b, Su et al., 2012, Yan et al., 2013, Zhang et al., 2016). In this review, we summarize methods that have enabled the BGM for quantification of a wide range of targets, such as protein, small organic molecule, metal ion, nucleic acid molecules and enzyme activities.