Abstract
Normal reproductive functioning is critically dependent on pulsatile secretion of luteinising hormone (LH). Assessment of LH pulsatility is important for the clinical diagnosis of reproductive disorders, but current methods are hampered by frequent blood sampling coupled to expensive serial immunochemical analysis. Here, we report the development and application of a Robotic APTamer-enabled Electrochemical Reader (RAPTER) electrochemical analysis system to determine LH pulsatility. Through selective evolution of ligands by exponential enrichment (SELEX), we identify DNA aptamers that bind specifically to LH and not to related hormones. The aptamers are integrated into electrochemical aptamer-based (E-AB) sensors on a robotic platform. E-AB enables rapid, sensitive and repeatable determination of LH concentration profiles. Bayesian Spectrum Analysis is applied to determine LH pulsatility in three distinct patient cohorts. This technology has the potential to transform the clinical care of patients with reproductive disorders and could be developed to allow real-time in vivo hormone monitoring.
Highlights
Normal reproductive functioning is critically dependent on pulsatile secretion of luteinising hormone (LH)
In order to address the challenges of clinical LH monitoring, we designed an aptamer-enabled electrochemical robotic platform based on the integration of multiple technologies
50 μl of sample is required for the measurement, and LH concentration profile can be generated from the signal response of the potentiostat
Summary
Normal reproductive functioning is critically dependent on pulsatile secretion of luteinising hormone (LH). Bayesian Spectrum Analysis is applied to determine LH pulsatility in three distinct patient cohorts This technology has the potential to transform the clinical care of patients with reproductive disorders and could be developed to allow real-time in vivo hormone monitoring. Altered patterns of LH pulse secretion have been linked to hypothalamic dysfunction, resulting in numerous reproductive disorders, including polycystic ovary syndrome (PCOS)[2], hypothalamic amenorrhoea[3] and delayed or precocious puberty[4] It is not currently feasible in routine clinical practice to measure LH pulsatility to determine altered secretion patterns because to do so is extremely resource intensive. Better technologies for hormone sensing, that could in the future be adapted for continuous sensing as an individual undergoes their normal daily routine, would revolutionise the clinical care of patients with reproductive disorders. E-AB sensors neither require washing, separations, chromatographic steps, nor expensive equipment, so are excellent choices as an approach for continuous, low-cost sensing that in future could be adaptable for in vivo sensing of numerous hormones
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