Interest in the types of device we associate with Fitbit products shows that consumers have developed an insatiable appetite for personal health information. Traditionally, biosensing was mainly used for the diagnosis and monitoring of disease states, with glucose monitoring for diabetics making up the lion’s share of the continuous medical biosensing market.
Now lifestyle devices have started to reach the realm of clinical quality diagnostic information, for example the diagnosis of atrial fibrillation by the Apple Watch [1].
Manufacturers of glucose monitors have responded by making their devices available over-the-counter to non-diabetic athletes [2,3]. Similarly, existing medical devices are being connected to smartphones and smartwatches to better integrate into patients’ lifestyles [4].
As an implant developer, I can see huge potential to improve biosensing systems through advances in miniaturisation and wireless power, but I also see exciting new approaches on the horizon that could meet this demand for accurate, reliable, affordable, discrete, and long-term biosensing solutions.
In this blog:
- External biosensing
- Minimally invasive biosensing
- Active implantables
- Passive implantables
- Outlook for biosensing
External biosensing
External biosensing has a long history in medical applications, but in the last ten years has also attracted keen interest from lifestyle product developers.
In measuring blood oxygenation, it is common to use a simple light-based pulse oximeter instead of a desktop PC-sized instrument for blood gas analysis, and non-invasively sample a patient’s blood oxygen saturation through the skin (as is done by many consumer smart-watches on the market).
For other analytes of interest, such as glucose, the goal of making external biosensing work has been elusive. Glucose is present in the body in much lower concentrations than haemoglobin, and therefore much harder to measure directly. The fraction of light absorbed by glucose relative to everything else is tiny and a signal is very hard to extract. Non-invasive sensors therefore sometimes measure signals that correlate indirectly with the glucose such as light scattering from the skin, or the analyte levels in sweat [5,6].
These quantities can hold weak or changing relationships with the target, especially in non-laboratory conditions, and are often surrounded by other molecules with similar properties. A few years ago Google attempted to create a contact lens that could monitor blood glucose non-invasively, however the project was discontinued due to measurement noise and time lag between the glucose sampled in tears, and the real concentration in the blood [7].
As devices become more sensitive and signal processing and machine learning methods evolve, non-invasive systems may start to show sufficient precision and accuracy to support clinical decision making. The time for non-invasive biosensors may come, but for now biosensors for many analytes need to be in close proximity to the source by measuring either blood or interstitial fluid directly.
Minimally invasive approaches
Another approach to biosensing is to keep the bulk of the biosensing system external to the body but to insert a small sensor probe through the skin. Direct contact with the tissue and analytes of interest enables much more selective sensing approaches.
The functionalisation of electrodes inserted into the body allows direct interaction with the analyte to be measured, and enables an accuracy and time response upon which treatment decisions can be made.
In practice such devices can only be worn for about 2 weeks before they need replacement, due to the risk of infection that comes with piercing the skin, or the chance that the wearable element might get snagged or lose adhesion. This is acceptable for many applications but does limit the potential for long term, preventative, or consumer applications.
Active implantables
For longer term sensing, devices can be fully implanted in the body. These keep the sensing elements encapsulated within the patient but communicate with an external device, thereby removing the ongoing infection risk of piercing the skin.
Such devices require electronics and power storage to enable sensor measurements. These components must be contained in a hermetically sealed package. This adds to the implant volume and necessitates a rigid form factor, which can lead to irritation of surrounding tissue as the user moves.
The presence of non-biological material also engages the body’s defence mechanisms against foreign substances. In the long term, a sensor will fall foul of the foreign body response (FBR), whereby it is encapsulated in fibrous tissue or cells, with the effect of isolating the sensor from the analytes of interest and introducing measurement delay.
The added complexity of energy storage and hermeticity in such a small space also adds to the device cost; this is acceptable for serious conditions but limits the availability of such technologies for a broader swathe of uses. The development of smaller and lower cost active implants will enable exciting new applications, but are there existing measurement technologies that could be cleverly utilised without the need for energy storage and conventional electronics?
Passive implantables
One exciting approach to achieving long-lived small form-factor biosensing solutions is to strip implantable sensors back to the absolute minimum; that is to create simple transducers of analytes of interest with minimal electronic components – “passive” implantables.
I use this term for an implant that is designed not to require complex hermetic packaging as it contains no battery, and minimal electronics that can be manufactured from inert materials.
As an example, imagine an LC oscillating circuit whereby the capacitive value changes in relation to an analyte’s concentration, for example through the swelling of a hydrogel [8]. The resonant frequency of the circuit, which can be measured externally, now maps back to the analyte of interest.
The simplicity of passive implantables makes for an interesting set of properties. First, it allows them to be small and low cost. Small size, and potentially reduced stiffness, would reduce the burden of implantation and could aid with the development of injectable or other minimally invasive implantation methods. Figure 1 shows the potential size reduction of a passive implantable compared to an active sensor. For context, figure 2 compares both to the approximate size of a battery powered neurostimulator.
Ideally, the device would be self-administered (like the patches used in continuous glucose monitors) or require only a very quick implantation procedure by a trained pharmacist. Reducing the cost to manufacture and the cost to implant would be powerful levers in expanding the potential market and encouraging a greater range of applications.
Once implanted, smaller devices have less of an effect on the surrounding tissue, which can aid in reducing the FBR. This has the potential to extend the device’s usable lifetime – with corresponding benefits for long-term uses like blood glucose monitoring [9]. Careful material choices could make these components inherently biocompatible, and in some cases even completely biodegradable [10].
Owing to the absence of electronics to “memorise” continual measurements, passive implantables must be used in conjunction with an external reading device. If intermittent readings are required the external device can function like a “flash” glucose monitor, whereby the user waves a reader (or smartphone) in proximity to the implant. If a continuous measurement system is desired, this external device would need to be “wearable”.
Of course, the advantage of a wearable used with a passive implantable sensor over the minimally invasive kind is that the wearable can easily be removed. The patient can leave it off, for example, while in the shower or sleeping, in applications where there is no health impact of missed measurements and the user desires maximal flexibility.
Beyond glucose monitoring, one potential application of passive implantables would be to enrich the data that can be collected in clinical trials. In this context, wearables are increasingly used to monitor patient cohorts, and passive implantables could add biochemical sensing to the set of collected data used to better understand the condition of patients and the effect of treatments. This could be achieved without an unreasonable cost implication for the study.
Passive implantables are not without their specific challenges. First and foremost, the core sensing technology needs to be long-lived and stable. In use, reading the sensor will likely rely on an analogue signal, which means that the comms link itself adds to measurement noise. Another interesting challenge of passive implant design lies in the potential for data security issues. They can be read wirelessly, so medical information may potentially be readable by devices near the user.
Outlook
Consumers and patients want biosensors that fit seamlessly into their lives, but we still need sensors that are clinically accurate, and for many applications that means sensors that need to go under the skin, are low in cost, and offer long lifetimes.
Passive implantables are a particularly exciting prospect for filling this niche. Physical implantation gets them close enough to the bio-signs of interest to give the required accuracies, simple structures make them small and low impact on the body, and the lack of electronic components helps add to their inherent biocompatibility. This combination of properties could allow the expansion of biosensing to more bio-signs and to more patients and, eventually, consumers.
TTP designs and develops next-generation medical implants using a holistic multi-disciplinary approach to identify custom solutions for each specific case. We run development programmes from specification of top-level requirements through to setting up supply chains and transfer to manufacturing. Please reach out if you would like to discuss anything in this blog, or technology for biosensing product development more generally.
About TTP's Biosensing team
Partnering with TTP's Biosensing consulting team means working with experts who understand the biosensor industry inside out. Whether navigating uncharted territories, supporting your next innovation or accelerating time to market, we solve complex challenges with engineering and scientific rigour, finding and retiring risks early to deliver high-impact results. When your internal bandwidth is constrained, TTP is ready to deliver. See our work in biosensor product design and development.
References
01. Heart health notifications on your Apple Watch
02. Supersapiens
03. Abbott announces future of biowearables at consumer electronics show
04. Garmin becomes first to integrate real-time Dexcom diabetes data into smartwatches
06. Sweat-Based in Vitro Diagnostics (IVD): From Sample Collection to Point-of-Care Testing (POCT)
07. Update on our Smart Lens program with Alcon
08. Hydrogel-based microsensors for wireless chemical monitoring
010. Fully implantable and bioresorbable cardiac pacemakers without leads or batteries
