Title: Intra-Uterine SENSing using a batteryless, wireless intrauterine platform (U-SENSE)
Funder: Department of Health and Social Care

Abstract: Development of USENSE is planned over 3 years (Gantt Chart): WP 1: Sensor Hardware (PDRA 1, HM lead): The prototype temperature sensor is approximately 35 mm long x 6 mm diameter but requires miniaturization (by approximately 50%) to enable widespread use. To accomplish this, we will use unpackaged chips, re-design the antenna and develop assembly and packaging processes. The DO sensor is a two-electrode amperometric system using Pt microelectrodes. It measures DO using a variation on an amperometric method that significantly reduces the current requirements. The pH sensor is based on a sol-gel Iridium Oxide electrode. The sensors will be packaged behind a gas-permeable biocompatible membrane, integrated in a single chip and tested in a simulated environment. Packaging of the sensors will ensure that the DO and pH sensors make contact with the surrounding fluid. The system will be tested for biofouling using mock physiological fluid and results validated by commercial reference sensors. Forty devices will be manufactured for use in WP4. Sterilization prior to in-patient testing will be performed with ethylene oxide (outsourced to Anderson Caledonia). WP 2: Software (PDRA 2, HM lead) The receiver, which is mounted on a belt worn around the waist, needs to decrease in size, making it unobtrusive and comfortable for long-term wear. The battery is the main barrier to belt miniaturization; new ultra-thin Lithium-polymer batteries will be sourced and incorporated into the support belt. 3D printing will be used to prototype the packaging. The belt antenna will be redesigned using simulation to maximize signal transmission. The design will be optimized (with medical product consultants and patient users), ensuring that the end product is thinner, sleeker with a softer feel. PPI will also be important in assuring end-user comfort and privacy. Data is transmitted to a smart-phone that communicates with the receiver via Bluetooth. An upgraded version of the current Android app will be developed (together with user feedback). Data analysis and interpretation will be performed off line and the results provided to the users and their study clinicians. WP 3: Identification and integration of end-user requirements (YC lead) and health economics evaluation (LY lead) We will hold workshops, focus groups and face-to-face interviews with users to continue to identify their requirements at each stage of the design process, in particular around the belt antenna and the phone App. End-user requirements will be considered in all other work packages to ensure requirements are practical and achievable. A market survey has been initiated to ensure that the physical design fits in with the perspectives of end users, patients and clinicians. A health economics evaluation will be initiated based on these outcomes. Where required, the prototype design will be modified or second-generation prototypes produced to ensure product acceptability. WP 4: Clinical pilot study (YC lead) A comparative feasibility study (Appendix E & F) will be performed on women with unexplained subfertility (n=15) and women with normal fertility (recruited from egg donors) (n=15), using the device for up to 30 days. Devices will be implanted as an outpatient procedure without general anaesthetics. The main outcomes measured will be feasibility in terms of recruitment and retention in the study, participant acceptability of the device, placement and function of the device and data collection success rates (from device to receiver to app). Data recorded from the device will be correlated with endogenous and exogenous biological variables (e.g. hormones, serum markers, ultrasound scan findings, clinical vital signs) to derive diagnostic analytic algorithms. Adverse events and safety issues will be evaluated. WP5: Commercialisation strategy This work plan initiates key processes that build a strong business case for future injection of funds.

Lay abstract: One in six couples have problems becoming pregnant. In a quarter of couples, no abnormality is found even after investigations. In many cases the womb is likely to be the key cause, but at present no reliable tests are available to assess this. In vitro fertilisation (IVF) is the key technique for treating subfertility (in ability to conceive naturally) costing over &pound;300 million year on year and increasing (UK). However, IVF has only a 30% success rate per treatment cycle. From IVF, and experimental studies in humans, doctors have learnt that there are three key parameters which are known to determine whether the embryo can develop are oxygen, temperature and pH1,2,4,5,7,8-10. Current methods of investigating the environment in the womb do not measure these parameters very well even though there are ways to help improve this environment if the problem is known, for example, improving oxygenation and blood flow by administering drugs (vasodilators) that increase the blood flow to the womb (oxygen)25,26; but the clinical benefits cannot be consistently shown in current studies due to our inability to select the right patients to treat. Currently, clinicians use ultrasound or invasive sampling of the womb, but these are only snapshot measurements of what the womb is like and cannot monitor daily or monthly changes, or the parameters considered most important by embryologists to the health of a fertilized egg (oxygen, pH and temperature). To solve this problem, we have developed a small batteryless sensor that can be placed inside the womb to measure oxygen, temperature and pH before conception. Our temperature sensor prototype has already been tested in animals (rabbits) and fifteen women. Funding is now sought to develop a complete integrated sensor that records pH, dissolved oxygen and temperature for further human testing.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH