Early-stage diagnosis of ovarian cancer via digital immunoassay on a SlipChip.

Ovarian cancer (OC) is one of the three major gynecologic malignancies and has the highest mortality rate because of the late diagnosis. Liquid biopsy based on serum protein biomarkers has demonstrated great potential for early diagnosis but remains limited by the analysis performance of conventional immunoassay technologies, such as chemiluminescence, and biomarkers, such as CA125. To address this challenge and achieve accurate early-stage diagnosis of OC, we developed a digital immunoassay on a SlipChip (DiSC) for quantitative analysis of a potential serum protein biomarker, Spondin-1 (SPON1). The DiSC system achieved a limit of detection (LoD) of 23 fg/µL for digital quantification of SPON1. The DiSC system was utilized to quantify the serum level of SPON1 in 357 clinical serum samples, including 63 from patients with benign ovarian tumors and 294 from patients with malignant ovarian cancer, ranging from stages I to IV. SPON1 concentrations were significantly different in samples from patients with malignant ovarian cancer. Notably, significantly different SPON1 levels were observed in early stages (I and II), in lymph node-negative cases (N0), and before metastasis (M0), suggesting that SPON1 could serve as a sensitive diagnostic biomarker for early-stage OC. The differential diagnostic model based on SPON1 levels quantified using DiSC demonstrated an area under the curve (AUC) of 0.8187 for early-stage OC, a significant improvement over CA-125 (AUC = 0.6967). For OC of all stages, the AUC was 0.8225, which could be further increased to 0.8750 when combined with CA-125. This showcases the potential of SPON1 as a novel biomarker for sensitive early-stage diagnosis of ovarian cancer and the capability of the DiSC system in discovering low-abundance biomarkers for disease diagnosis.

Combination-Lock SlipChip Integrating Nucleic Acid Sample Preparation and Isothermal LAMP Amplification for the Detection of SARS-CoV-2.

Nucleic acid analysis with an easy-to-use workflow, high specificity and sensitivity, independence of sophisticated instruments, and accessibility outside of the laboratory is highly desirable for the detection and monitoring of infectious diseases. Integration of laboratory-quality sample preparation on a hand-held system is critical for performance. A SlipChip device inspired by the combination lock can perform magnetic bead-based nucleic acid extraction with several clockwise and counterclockwise rotations. A palm-sized base station was developed to assist sample preparation and provide thermal control of isothermal nucleic acid amplification without plug-in power. The loop-mediated isothermal amplification reaction can be performed with a colorimetric method and directly analyzed by the naked eye or with a mobile phone app. This system achieves good bead recovery during the sample preparation workflow and has minimal residue carryover from the lysis and elution buffers. Its performance is comparable to that of the standard laboratory protocol with real-time qPCR amplification methods. The entire workflow is completed in less than 35 min and the device can achieve 500 copies/mL sensitivity. Thirty clinical nasal swab samples were collected and tested with a sensitivity of 95% and a specificity of 100% for SARS-CoV-2. This combination-lock SlipChip provides a promising fast, easy-to-use nucleic acid test with bead-based sample preparation that produces laboratory-quality results for point-of-care settings, especially in home use applications.