Clinic-on-a-Needle Array toward Future Minimally Invasive Wearable Artificial Pancreas Applications

Abstract

In order to reduce medical facility overload due to the rise of the elderly population, modern lifestyle diseases, or pandemics, the medical industry is currently developing point-of-care and home medical device systems. Diabetes is an incurable and lifetime disease, accountable for a significant mortality and socio-economic public health burden. Thus, tight glucose control in diabetic patients, which can prevent the onset of its late complications, is of enormous importance. Despite recent advances, the current best achievable management of glucose control is still inadequate, due to several key limitations in the system components, mainly related to the reliability of sensing components, both temporally and chemically, and the integration of sensing and delivery components in a single wearable platform, which is yet to be achieved. Thus, advanced closed-loop artificial pancreas systems able to modulate insulin delivery according to the measured sensor glucose levels, independently of patient supervision, represent a key requirement of development efforts. Here, we demonstrate a minimally invasive, transdermal, multiplex, and versatile continuous metabolites monitoring system in the subcutaneous interstitial fluid space based on a chemically modified SiNW-FET nanosensor array on microneedle elements. Using this technology, ISF-borne metabolites require no extraction and are measured directly and continuously by the nanosensors. Due to their chemical sensing mechanism, the nanosensor response is only influenced by the specific metabolite of interest, and no response is observed in the presence of potential exogenous and endogenous interferents known to seriously affect the response of current electrochemical glucose detection approaches. The 2D architecture of this platform, using a single SOI substrate as a top-down multipurpose material, resulted in a standard fabricated chip with 3D functionality. After proving the ability of the system to act as a selective multimetabolites sensor, we have implemented our platform to reach our main goal for in vivo continuous glucose monitoring of healthy human subjects. Furthermore, minor adjustments to the fabrication technique allow the on-chip integration of microinjection needle elements, which can ideally be used as a drug delivery system. Preliminary experiments on a mice animal model successfully demonstrated the single-chip capability to both monitor glucose levels as well as deliver insulin. By that, we hope to provide in the future a cost-effective and reliable wearable personalized clinical tool for patients and a strong tool for research, which will be able to perform direct monitoring of clinical biomarkers in the ISF as well as synchronized transdermal drug delivery by this single-chip multifunctional platform.

The “Bloodless” Blood Test: Intradermal Prick Nanoelectronics for the Blood Extraction-Free Multiplex Detection of Protein Biomarkers

“…Microneedles in the length of 300–500 μm were previously shown to enable in vivo transdermal monitoring of glucose levels in interstitial fluid (ISF); however, this insertion depth range does not allow microneedle elements to reach and rupture intradermal blood capillaries networks. 24 Therefore, longer microneedles are needed to fully penetrate and rupture the dermal layers and reach capillary depth for the subsequent capillary blood protein biomarkers detection. Figure 3 a shows a comparison of different needles–a 27G needle used in common venous blood extraction procedures, and representative 400 μm-long and 1 mm-long microneedle-embedded SiNW-FET arrays.…”

“… 14 − 17 Most of these systems’ applications have focused on drug delivery, 18 − 20 liquid biosamples extraction for ex situ analysis, 21 , 22 and glucose levels monitoring in diabetic individuals. 23 , 24 Currently reported microneedle-based sensing platforms are based on complex nonscalable fabrication procedures, often limiting the resulting devices’ reliability, accuracy, and real-world applicability. 25 − 28 Furthermore, all reported studies focused on the real-time intradermal detection of small molecular species, mostly glucose.…”

Remote Healthcare for Elderly People Using Wearables: A Review

“…In addition, an increasing interest in developing more and better biosensors to measure biosignals from the human body with a more “invasive” approach should also be noted. This invasive approach allows one, among other things, to perform more reliable readings of some physiological variables such as the level of glucose in the blood [ 126 ]. As already mentioned, the idea of building increasingly smaller devices opens up a vast amount of possibilities regarding the use of sensors that can be placed or inserted in parts of the human body without being uncomfortable or obstructive [ 127 ].…”

A self-contained and integrated microfluidic nano-detection system for the biosensing and analysis of molecular interactions

“…Combining the advantages of the traditional complementary metal oxide semiconductor manufacturing technology and the developed silicon industry, the latest developments in top-down manufacturing technology have paved the way for mass production of high-density and high-quality SiNW-FET biosensors. 9 SiNW-FET biosensors have enabled label-free rapid and sensitive biometric quantification in many emerging applications including drug screening and evaluation, 10 continuous medical health monitoring, 11 artificial olfactory devices, 12 artificial vision devices, 13 environmental monitoring, 14 wearable devices, 15 bionic electronic skin, 16 disease diagnosis, 17 pathogen identification, 18 real-time cell morphology observation, 19 affinity and kinetic analysis, 20 single nucleotide polymorphism detection, 21 multiple marker detection, 17 membrane potential measurement, 22 and many other fields. Compared to other detection technologies, SiNW-FET has broad application prospects, which make it very promising to be developed into a portable device for multiple tasks such as detection of pathogens and analysis of molecular interactions.…”