The Era of Digital Health: A Review of Portable and Wearable Affinity Biosensors

Abstract

Digital health facilitated by wearable/portable electronics and big data analytics holds great potential in empowering patients with real‐time diagnostics tools and information. The detection of a majority of biomarkers at trace levels in body fluids using mobile health (mHealth) devices requires bioaffinity sensors that rely on “bioreceptors” for specific recognition. Portable point‐of‐care testing (POCT) bioaffinity sensors have demonstrated their broad utility for diverse applications ranging from health monitoring to disease diagnosis and management. In addition, flexible and stretchable electronics‐enabled wearable platforms have emerged in the past decade as an interesting approach in the ambulatory collection of real‐time data. Herein, the technological advancements of mHealth bioaffinity sensors evolved from laboratory assays to portable POCT devices, and to wearable electronics, are synthesized. The involved recognition events in the mHealth affinity biosensors enabled by bioreceptors (e.g., antibodies, DNAs, aptamers, and molecularly imprinted polymers) are discussed along with their transduction mechanisms (e.g., electrochemical and optical) and system‐level integration technologies. Finally, an outlook of the field is provided and key technological bottlenecks to overcome identified, in order to achieve a new sensing paradigm in wearable bioaffinity platforms. Here, recent advances in portable and wearable affinity biosensors are summarized and highlighted. The key bottlenecks and opportunities for future wearable sensors for digital health are discussed.

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1906713 (1 of 30)
Review
The Era of Digital Health: A Review of Portable
and Wearable Affinity Biosensors
Jiaobing Tu, Rebeca M. Torrente-Rodríguez, Minqiang Wang, and Wei Gao*
Digital health facilitated by wearable/portable electronics and big data
analytics holds great potential in empowering patients with real-time diag-
nostics tools and information. The detection of a majority of biomarkers at
trace levels in body fluids using mobile health (mHealth) devices requires
bioaffinity sensors that rely on “bioreceptors” for specific recognition. Port-
able point-of-care testing (POCT) bioaffinity sensors have demonstrated
their broad utility for diverse applications ranging from health monitoring
to disease diagnosis and management. In addition, flexible and stretchable
electronics-enabled wearable platforms have emerged in the past decade as
an interesting approach in the ambulatory collection of real-time data. Herein,
the technological advancements of mHealth bioaffinity sensors evolved from
laboratory assays to portable POCT devices, and to wearable electronics,
are synthesized. The involved recognition events in the mHealth affinity
biosensors enabled by bioreceptors (e.g., antibodies, DNAs, aptamers, and
molecularly imprinted polymers) are discussed along with their transduction
mechanisms (e.g., electrochemical and optical) and system-level integration
technologies. Finally, an outlook of the field is provided and key technological
bottlenecks to overcome identified, in order to achieve a new sensing para-
digm in wearable bioaffinity platforms.
DOI: 10.1002/adfm.201906713
treatment.[3] Long-term health monitoring
supported by smartphone and wearable
technologies at both the micro- and mac-
roscale will encourage healthy lifestyles to
prevent and reduce health problems, pro-
vide means for patient-oriented chronic
disease management, reduce the fre-
quency of clinical visits, and provide per-
sonalized on-demand interventions at the
POC.[4]
With the emphasis of healthcare
shifting towards prevention and early
detection of diseases and monitoring of
chronic conditions, there is a growing
need for hassle-free, patient-centered
sensor technologies.[5] Portable devices
have demonstrated their utility in various
disease diagnosis and monitoring set-
tings; classic examples include commer-
cial blood glucose monitoring (BGM)
and colorimetric pregnancy test devices.
On the other side, wearable biosensors
with continuous monitoring capability
have developed from tracking of generic
physical biomarkers (e.g., temperature[6,7]
and pressure[8]) to more disease-specific applications such
as the management of diabetes.[9] Commercially wrist-worn
devices for physical activity tracking such as Apple Watch and
Fitbit, have become increasingly common among the general
public. A variety of continuous glucose monitoring devices
have also emerged in the market (e.g., Guardian REAL-Time by
Medtronic and FreeStyle Libre by Abbot). Among the mHealth
biosensors, one particularly attractive category is bioaffinity bio-
sensors that utilize a ‘bioreceptor’ for specific recognition of the
target analyte. The incorporation of bioaffinity elements with
high selectivity and sensitivity for the detection of trace-level
disease-relevant targets will consequentially broaden the land-
scape of the wearable sensor and the impact of digital health.
Since the conception of surface plasmon resonance (SPR)
detection of biospecific interaction,[10,11] bioaffinity sensors have
evolved from assays requiring complex and bulky laboratory-
based equipment to miniaturized portable systems that cater
to the decentralized or at-home analysis of disease biomarkers.
A brief history of the development of key bioaffinity recep-
tors and their incorporation in POC diagnostics (both portable
and wearable devices) is summarized in Figure 1. While port-
able bioaffinity sensing technologies with advanced biological
sample processing, rapid analysis in miniaturized fluidic
devices, and smartphone-enabled facile information extraction
have shown significant progress in realizing the potential of
J. Tu, Dr. R. M. Torrente-Rodríguez, Dr. M. Wang, Prof. W. Gao
Andrew and Peggy Cherng Department of Medical Engineering
California Institute of Technology
Pasadena, CA 91125, USA
E-mail: weigao@caltech.edu
The ORCID identification number(s) for the author(s) of this article
can be found under https://doi.org/10.1002/adfm.201906713.
1. Introduction
As the technologies of point-of-care testing (POCT) biosensors
advance, the potential of digital monitoring of biomarkers to
manage health,[1] enable rapid disease diagnosis[2] and provide
accurate prediction has also become apparent. Creative incorpo-
ration of sensor technologies with mobile phones has evolved
into a new field of POCT known as digital health or mobile
health (mHealth). mHealth promises to support healthcare
providers with at-home diagnosis and patient management,
and to facilitate communication between healthcare services
and patients. Driven by sensor technologies and big data ana-
lytics, the future of digital health promises the development
of a learning health system that will not only transform the
paradigm of disease management but also potentially clinical
Adv. Funct. Mater. 2020, 30, 1906713