Integration of cell phone imaging with microchip ELISA to detect ovarian cancer HE4 biomarker in urine at the point-of-care

Abstract

Ovarian cancer is asymptomatic at early stages and most patients present with advanced levels of disease. Lack of cost-effective methods that can achieve frequent, simple and non-invasive testing hinders early detection and causes high mortality in ovarian cancer patients. Here, we report a simple and inexpensive microchip ELISA-based detection module that employs a portable detection system, i.e., a cell phone/charge-coupled device (CCD) to quantify an ovarian cancer biomarker, HE4, in urine. Integration of a mobile application with a cell phone enabled immediate processing of microchip ELISA results, which eliminated the need for a bulky, expensive spectrophotometer. The HE4 level detected by a cell phone or a lensless CCD system was significantly elevated in urine samples from cancer patients (n = 19) than normal healthy controls (n = 20) (p < 0.001). Receiver operating characteristic (ROC) analyses showed that the microchip ELISA coupled with a cell phone running an automated analysis application had a sensitivity of 89.5% at a specificity of 90%. Under the same specificity, the microchip ELISA coupled with a CCD had a sensitivity of 84.2%. In conclusion, integration of microchip ELISA with cell phone/CCD-based colorimetric measurement technology can be used to detect HE4 biomarker at the point-of-care (POC), paving the way to create bedside technologies for diagnostics and treatment monitoring.

Шляхи Розвитку Мобільної Медицини

“…• управління пристроєм або дисплеєм для збе-рігання, аналізу та передачі даних медичного обстеження конкретного пацієнта (наприклад, віддалений моніторинг даних пацієнта від при-ліжкового монітору) [15]; • перетворювачі інформації (наприклад, при-єднання датчику аналізу рівня глюкози в крові пацієнта на мобільну платформу, що здійснює обробку даних) [26]; • обчислювачі інформації конкретного пацієнта з подальшим аналізом для діагностики або лікування (наприклад, додаток, що обчислює дози випромінювання на основі власних даних пацієнта). Стосовно приладів третьої (а також частки пер-шої) групи, їх можна об'єднати в такі підгрупи:…”

Cellphone-based diagnostic devices

“…This has been demonstrated via analysis of human Immunoglobulin G (IgG) on chips via a process that analyzed signal intensities of gold nanoparticles, in combination with silver staining, to determine proportional IgG concentrations [60]. Moreover, CMD design using microchip ELISA has been used to detect ovarian cancer marker [human epididymis protein 4 (HE4)], a process that underscores the potential for CMD-based microfluidic devices for POC diagnostics [61]. Following a set of operation steps (including running an analytically based cellphone application), this chip demonstrated a sensitivity of 89.5 % and a specificity of 90 % for clinical HE4 detection.…”

Microdevices for Non-Invasive Detection of Bladder Cancer

“…By enabling doctors to take unobtrusive, straightforward measurements of patient physiology, such technologies have brought medical monitoring into patients' daily lives for long-term, continuous observation of individual medical cases. Commercially available wearable sensors provide near-instant readouts on parameters such as heart rate, temperature, and oxygen saturation in a user-friendly manner [120]; even more directly relevant to bladder cancer microfluidic devices are phone-based sensors with functionalities such as calculating quantitative ELISA assay results [121] and detecting point mutations in tumor samples [122]. At a deeper level, wearable and phone-based sensors point to further guiding principles in the development of microfluidic devices to assay bladder cancer: the importance of designing devices that are compatible with hospitals' pre-existing equipment and with patients' daily regimens.…”