Fully Integrated Biochip Platforms for Advanced Healthcare

Recent advances in microelectronics and biosensors are enabling developments of innovative biochips for advanced healthcare by providing fully integrated platforms for continuous monitoring of a large set of human disease biomarkers. Continuous monitoring of several human metabolites can be addressed by using fully integrated and minimally invasive devices located in the sub-cutis, typically in the peritoneal region. This extends the techniques of continuous monitoring of glucose currently being pursued with diabetic patients. However, several issues have to be considered in order to succeed in developing fully integrated and minimally invasive implantable devices. These innovative devices require a high-degree of integration, minimal invasive surgery, long-term biocompatibility, security and privacy in data transmission, high reliability, high reproducibility, high specificity, low detection limit and high sensitivity. Recent advances in the field have already proposed possible solutions for several of these issues. The aim of the present paper is to present a broad spectrum of recent results and to propose future directions of development in order to obtain fully implantable systems for the continuous monitoring of the human metabolism in advanced healthcare applications

Skin-Integrated wearable systems and implantable biosensors: a comprehensive review

Biosensors devices have attracted the attention of many researchers across the world. They have the capability to solve a large number of analytical problems and challenges. They are future ubiquitous devices for disease diagnosis, monitoring, treatment and health management. This review presents an overview of the biosensors field, highlighting the current research and development of bio-integrated and implanted biosensors. These devices are micro- and nano-fabricated, according to numerous techniques that are adapted in order to offer a suitable mechanical match of the biosensor to the surrounding tissue, and therefore decrease the body’s biological response. For this, most of the skin-integrated and implanted biosensors use a polymer layer as a versatile and flexible structural support, combined with a functional/active material, to generate, transmit and process the obtained signal. A few challenging issues of implantable biosensor devices, as well as strategies to overcome them, are also discussed in this review, including biological response, power supply, and data communication.This research was funded by FCT- FUNDAÇÃO PARA A CIÊNCIA E TECNOLOGIA, grant numbers: PTDC/EMD-EMD/31590/2017 and PTDC/BTM-ORG/28168/2017

Investigating pipeline and state of the art blood glucose biosensors to formulate next steps

Ten years on from a review in the twentieth issue of this journal, this contribution assess the direction research in the field of glucose sensing for diabetes is headed and various technologies to be seen in the future. The emphasis of this review was placed on the home blood glucose testing market. After an introduction to diabetes and glucose sensing, this review analyses state of the art and pipeline devices; in particular their user friendliness and technological advancement. This review complements conventional reviews based on scholarly published papers in journals

Design and Implementation of Signal Processing Circuitry for Implantable Sensors

Recent technological advancements in integrated circuits and medical technology have made real-time monitoring of physiological factors possible. One such important physiological factor to be measured is glucose. Continuous monitoring of glucose is extremely important for patients with diabetes as it helps make optimal treatment decisions. To enable continuous measurement, a chip containing the sensors and the electronic circuitry is implanted in the human body. This implanted chip provides for continuous measurement and helps reduce inconvenience caused to diabetic patients. A potentiostat forms an integral part of a sensor signal processing circuit. In this thesis the design and simulation of an on-chip potentiostat circuit has been presented. A potentiostat is needed to maintain a constant potential, so that the sensor can measure glucose. This design has been fabricated using a 0.35-m bulk CMOS process available through MOSIS

Smart implanted access port catheter for therapy intervention with pH and lactate biosensors.

Totally implanted access ports (TIAP) are widely used with oncology patients requiring long term central venous access for the delivery of chemotherapeutic agents, infusions, transfusions, blood sample collection and parenteral nutrition. Such devices offer a significant improvement to the quality of life for patients and reduced complication rates, particularly infection, in contrast to the classical central venous catheters. Nevertheless, infections do occur, with biofilm formation bringing difficulties to the treatment of infection-related complications that can ultimately lead to the explantation of the device. A smart TIAP device that is sensor-enabled to detect infection prior to extensive biofilm formation would reduce the cases for potential device explantation, whereas biomarkers detection within body fluids such as pH or lactate would provide vital information regarding metabolic processes occurring inside the body. In this paper, we propose a novel batteryless and wireless device suitable for the interrogation of such markers in an embodiment model of an TIAP, with miniature biochemical sensing needles. Device readings can be carried out by a smartphone equipped with Near Field Communication (NFC) interface at relative short distances off-body, while providing radiofrequency energy harvesting capability to the TIAP, useful for assessing patient's health and potential port infection on demand

Enzyme Biosensors for Point-of-Care Testing

Biosensors are devices that integrate a variety of technologies, containing biology, electronics, chemistry, physics, medicine, informatics, and correlated technology. Biosensors act as transducer with a biorecognition element and transform a biochemical reaction on the transducer surface directly into a measurable signal. The biosensors have the advantages of rapid analysis, low cost, and high precision, which are widely used in many fields, such as medical care, disease diagnosis, food detection, environmental monitoring, and fermentation industry. The enzyme biosensors show excellent application value owing to the development of fixed technology and the characteristics of specific identification, which can be combined with point-of-care testing (POCT) technology. POCT technology is attracting more and more attention as a very effective method of clinic detection. We outline the recent advances of biosensors in this chapter, focusing on the principle and classification of enzyme biosensor, immobilization method of biorecognition layers, and fabrication of amperometric biosensors, as well as the applications of POCT. A summary of glucose biosensor development and integrated setups is included. The latest applications of enzyme biosensors in diagnostic applications focusing on POCT of biomarkers in real samples were described

Microfluidic biosensor systems for real-time in vivo clinical bioanalysis

The aim of this thesis was to develop online biosensing systems for dialysate tissue metabo- lite detection in real time, to provide an insight into the health of tissue in various in vivo applications. An autocalibration system was developed using LabSmith programmable components to improve the accuracy of results obtained over long monitoring times. A method of col- lecting dialysate into storage tubes for online analysis while retaining temporal resolution was developed and validated. Microfluidic biosensor systems were developed for online measurement of glucose and lactate. One approach employed the use of biosensors, using a combined needle electrode with enzyme encapsulated in a hydrogel layer. The dynamic range of the biosensors was extended by adding an outer polyurethane layer. An alternative approach used automated syringe pumps and valves to develop a microfluidic system for in-flow enzyme addition to the dialysate stream. The existing rsMD system was applied for detection of tissue ischaemia during and after free flap surgery, by measuring dialysate glucose and lactate levels in real time. The system was able to detect flap failure, both during surgery and afterwards in the intensive therapy unit (ITU), much earlier than traditional methods. The rsMD system was adapted to enable monitoring of lactate levels in two dialysate streams and was applied for monitoring isolated porcine kidneys during two methods of cold preservation and subsequent re-warming. Significant differences in the lactate concentrations were observed between the two techniques. The system was extended for use with human transplant kidneys and with both porcine and human pancreases. A novel 3D printed wearable biosensor system was developed for direct integration with a clinical microdialysis probe. The system considerably improved the lag time and dispersional smearing compared with the existing rsMD system. The device was used in a proof-of-concept study with wireless potentiostats to monitor cyclists during exercise.Open Acces

Current and Emerging Technology for Continuous Glucose Monitoring

Diabetes has become a leading cause of death worldwide. Although there is no cure for diabetes, blood glucose monitoring combined with appropriate medication can enhance treatment efficiency, alleviate the symptoms, as well as diminish the complications. For point-of-care purposes, continuous glucose monitoring (CGM) devices are considered to be the best candidates for diabetes therapy. This review focuses on current growth areas of CGM technologies, specifically focusing on subcutaneous implantable electrochemical glucose sensors. The superiority of CGM systems is introduced firstly, and then the strategies for fabrication of minimally-invasive and non-invasive CGM biosensors are discussed, respectively. Finally, we briefly outline the current status and future perspective for CGM systems.This work was supported by the National Natural Science Foundation of China (61471233, 21504051), the Program for Professor of Special Appointment (Eastern Scholar) at SIHL, the Sailing Project and Basic Research Program from Science and Technology Commission of Shanghai Municipality (14YF1410600, 14JC1406402), Shuguang and ChenGuang project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation (14SG52, 13CG62), the key subject of Shanghai Polytechnic University (Material Science and Engineering, XXKZD1601)