Coaright measures the coagulation status of blood using a cantilever-based opto-mechanical method sensitive to viscoelastic variation of blood during coagulation.
The system consists of a reader unit that houses the electronics, light source, electromagnetic coil, heater and photodetectors and a disposable cartridge inserted in the reader unit. The blood sample is placed into a microfluidic channel through an inlet and flows by capillary motion into the cartridge where a resonant vibrating optical fiber (cantilever) and a pick-up optical fiber are aligned with a small gap in between. Near mechanical resonance of the vibrating fiber is achieved by magnetic actuation using a small nickel ring attached at the free end of the fiber.
The key innovative feature of the system consists of a fluid stop region which separates blood interaction and measurement regions of the vibrating fiber. The pick-up fiber collects a clear optical signal avoiding scattering and optical losses which results in high signal-to-noise ratio optical output.
As blood starts to coagulate, both its viscosity and elasticity increases, leading to a decrease in fiber deflection (resonant frequency) and thus in a sharp decrease in the amplitude of the optical signal from which PT/INR is derived (Yaras et al. 2017).
Pre-clinical validation - study outcome:
- 160 patients undergoing vitamin K antagonists (VKAs) therapy who visited and/or were admitted to Istanbul Kartal Kosuyolu High Specialization Training and Research Hospital, between June 2019 and February 2020.
- Overall, both the reference laboratory method and our novel PoC device were able to measure all 160 patient’s prothrombin times with INR ranging from 0.98 to 6.42. Strong correlations were observed between our device and the reference laboratory system with correlation coefficients of 0.93 for the entire cohort, 0.89 for the outpatients (N=141) and 0.98 for the inpatients (N=19) populations. Our device remained performant in areas where commercial PoC devices often face difficulties: PT/INRs accuracy in the supratherapeutic range and of inpatients undergoing additional treatments and interventions.
Figure 1. Pearson correlation coefficient and Bland-Altmann difference plot analysis of PT values measured by our viscosity-based PoC device and compared to the reference laboratory method. Both assays showed a strong degree of correlation with r=0.93 (95% CI 0.906 to 0.949, p <0.0001; R2 of 87%) for the entire cohort (A), r=0.89 (95% CI 0.843 to 0.916, p <0.0001; R2 of 78%) for the outpatients (C) and r= 0.98 (95% CI 0.941 to 0.991, p <0.0001; R2 of 96%) for the inpatients (E). The Bland–Altman difference plot showed mean differences (average bias) of -0.92 seconds with 95% limits of agreement of -10.4 to 8.52 for the entire cohort (B), -0.66 seconds with 95% limits of agreement of -10.7 to 8.84 for the outpatients (D) and -2.84 seconds with 95% limits of agreement of -11.1 to 5.43 (F). Dotted lines represent the 95% limits of agreement.
- (Under Review by IJLH) Aslan Polat, B., Muldur, S.K., Indelen, C., Urey,H., Uygun Kizmaz, Y., Olcer, S., Kirali, M.K., and Urey H. (2021) Performance evaluation of a novel viscosity-based PoC coagulometer for the measurement of prothrombin time in patients on VKA therapy.
- Yaraş, Y.S., Gündüz, A.B., Sağlam, G., Ölçer, S., Civitçi, F., Baris, I., Yaralioğlu, G. and Urey, H. (2017). Coagulation measurement from whole blood using vibrating optical fiber in a disposable cartridge. Journal of biomedical optics, 22(11):117001.
- Yaras, Y.S., Cakmak, O., Gunduz, A.B., Saglam, G., Olcer, S., Mostafazadeh, A., Baris, I., Civitci, F., Yaralioglu, G.G. and Urey, H., (2017). Disposable cartridge biosensor platform for portable diagnostics. In Optics and Biophotonics in Low-Resource Settings III (Vol. 10055, p. 100550O). International Society for Optics and Photonics.
- Mostafazadeh, A., Yaralioglu, G.G. and Urey, H., (2016). Optical fiber array based simultaneous parallel monitoring of resonant cantilever sensors in liquid. Sensors and Actuators A: Physical, 242, pp.132-139.
- Cakmak, O., Ermek, E., Kilinc, N.E.C.M.E.T.T.İ.N., Bulut, S., Baris, I., Kavakli, I.H., Yaralioglu, G.G. and Urey, H., (2015). A cartridge based sensor array platform for multiple coagulation measurements from plasma. Lab on a Chip, 15(1), pp.113-120.
- Cakmak, O., Kilinc, N., Ermek, E., Mostafazadeh, A., Elbuken, C., Yaralioglu, G.G. and Urey, H., (2014), January. LoC sensor array platform for real-time coagulation measurements. In 2014 IEEE 27th International Conference on Micro Electro Mechanical Systems (MEMS) (pp. 330-333). IEEE.
- Cakmak, O., Elbuken, C., Ermek, E., Mostafazadeh, A., Baris, I., Alaca, B.E., Kavakli, I.H. and Urey, H., (2013). Microcantilever based disposable viscosity sensor for serum and blood plasma measurements. Methods, 63(3), pp.225-232