Development and preliminary validation of infrared spectroscopic device for transdermal assessment of elevated cardiac troponin

Abstract

Background The levels of circulating troponin are principally required in addition to electrocardiograms for the effective diagnosis of acute coronary syndrome. Current standard-of-care troponin assays provide a snapshot or momentary view of the levels due to the requirement of a blood draw. This modality further restricts the number of measurements given the clinical context of the patient. In this communication, we present the development and early validation of non-invasive transdermal monitoring of cardiac troponin-I to detect its elevated state. Methods Our device relies on infrared spectroscopic detection of troponin-I through the dermis and is tested in stepwise laboratory, benchtop, and clinical studies. Patients were recruited with suspected acute coronary syndrome. Results We demonstrate a significant correlation (r = 0.7774, P < 0.001, n = 52 biologically independent samples) between optically-derived data and blood-based immunoassay measurements with and an area under receiver operator characteristics of 0.895, sensitivity of 96.3%, and specificity of 60% for predicting a clinically meaningful threshold for defining elevated Troponin I. Conclusion This preliminary work introduces the potential of a bloodless transdermal measurement of troponin-I based on molecular spectroscopy. Further, potential pitfalls associated with infrared spectroscopic mode of inquiry are outlined including requisite steps needed for improving the precision and overall diagnostic value of the device in future studies.

A novel breakthrough in wrist-worn transdermal troponin-I-sensor assessment for acute myocardial infarction

“… 12 The transdermal-ISS device is designed to be sensitive largely to the wavelengths of interest for the detection of troponin. 13 However, the exact nature of the biomarker [troponin T-I-C, binary complexes (I-C), free submits (T and C), and fragments or related molecules thereof) tracked by the spectroscopy can be speculative. Moreover, co-presenting biomarkers such as CKMB, h-FABP, and NT-proBNP, albeit small, could contribute to the optical absorption window of hs-cTnI.…”

“…The detailed development of the device is outlined elsewhere. 13 Briefly, our previous study included four phases of development. First, in an ex vivo exploratory work, we tested blood samples of patients ( n = 30) with various cTnI levels on a research-grade attenuated total reflectance–based infrared spectrometer.…”

“…Between-group comparisons were conducted using Pearson’s chi-square test (for the goodness of fit) or Fisher’s exact test (for categorical variables) and Student’s t -test (for continuous variables) after testing for normal distribution using the Kolmogorov–Smirnov test. Using our previous 13 AUC for differentiating elevated troponins of 0.85 and 0.5 for a null hypothesis value, assuming that at least 70% of patients with suspected MI will have elevated troponin value, a sample size of at least 40 in the test set was estimated to provide 90% power, assuming an α -level of 0.05.…”

“…In this regard, we have recently reported the development of a novel wrist-worn transdermal infrared spectrophotometric sensor (transdermal-ISS) that can assess raised troponin-I levels based on infrared spectroscopy. 13 Infrared spectroscopy can interrogate the material at the molecular level and is one of the cornerstones of analytical tools used to study structural and compositional chemistry. 14 The most significant advantage is that a sensitive sensor can produce results within 5 min, without collecting blood and transferring the sample to the testing device.…”

Early Changes in Acute Myocardial Infarction in Pigs: Achieving Early Detection with Wearable Devices

“…No commercial products currently available have the ability to detect troponin or lactate levels. Some prototypes are being tested, including the transdermal cardiac injury sensor we used in our study, which has shown good correlation with high-sensitivity cardiac troponin I blood samples in the clinic [ 19 ]. For lactate biosensors, Rockley’s Bioptx Pro platform has cooperated with Medtronic to start the application for clinical verification [ 20 ].…”