Magneto‐Nanomechanical Array Biosensor for Ultrasensitive Detection of Oncogenic Exosomes for Early Diagnosis of Cancers

Abstract

The Advisory Committee on Cancer for the World Health Organization suggests that "a third of cancers are curable if diagnosed early". [3] Traditional methods of cancer diagnosis are based primarily on histo-pathological examination and imaging of the tumor tissue, which are the current gold standards. [4] However, these methods tend to detect specific lesions only when they are formed in the middle and later stages of cancer development, and are not suitable for screening early cancers in a large population. In the early stage of cancer development, before the formation of specific lesions, cancer cells in the body begin to release a few cancer markers related to cancer formation and metastasis. [5] At this time, if a highly sensitive detection method can be available to detect the very low concentration of markers in body fluids, it will bring great potential for the early detection and diagnosis of cancer. In addition, traditional methods are invasive, and inaccurate biopsy positioning can cause sampling errors. X-ray screening and histo-pathological evaluation rely heavily on the individual's expertise, which causes discrepancies between individual and laboratory-reported results. [6] All these limitations indicate the need for highly sensitive and minimally invasive techniques for early diagnosis and treatment of cancers. In comparison, liquid biopsies can offer early discovery and a non-invasive approach.In recent years, cancer markers in body fluids, such as circulating tumor-derived proteins (carcinoembryonic antigen, prostate-specific antigen), circulating tumor cells, and circulating tumor DNA, [7] have been the most common biomarkers for cancer diagnosis and assessment of treatment efficacy. However, these biomarkers have several shortcomings in early-stage cancer diagnosis. Circulating tumor-derived protein markers are compromised by high false positive rates, which can lead to overdiagnosis and, in some cases, to unnecessary anticancer treatment. [8] The fraction of circulating tumor DNA in total circulating free DNA is usually very low and often < 0.01%; therefore, this can complicate early detection. [9] Circulating tumor cells are tumor cells that have detached from the primary tumor, with extremely low quantities. Exosomes are a class of nanoscale vesicles secreted by cells, which contain abundant information closely related to parental cells. The ultrasensitive detection of cancer-derived exosomes is highly significant for early noninvasive diagnosis of cancer.Here, an ultrasensitive nanomechanical sensor is reported, which uses a magnetic-driven microcantilever array to selectively detect oncogenic exosomes. A magnetic force, which can produce a far greater deflection of microcantilever than that produced by the intermolecular interaction force even with very low concentrations of target substances, is introduced. This method reduced the detection limit to less than 10 exosomes mL −1 . Direct detection of exosomes in the serum of patients with breast cancer and in healthy people showed a signifi...

A Genosensor Based on the Modification of a Microcantilever: A Review

“…In addition to the above optical and electrical methods, the magnetic force also can be used for the ultrasensitive detection of a microcantilever, by establishing a link between very weak molecular interaction and the magnetic force [ 79 , 80 ]. Meanwhile, there are some special signal extraction methods adapted to the genetic probe modification of a microcantilever.…”

Application of 3D printing technology in tumor diagnosis and treatment

“…Among the methods used for the early detection of cancer, biosensors are currently widely used because of their high sensitivity, high specificity, good stability and LOD [37,38]. According to its sensitive elements, biosensors are divided into five categories: immunosensor, enzyme sensor, microbial sensor, organelle sensor and tissue sensor [39][40][41][42][43].…”

CRISPR/Cas12a‐loaded intelligent DNA hydrogel for universal and ultrasensitive exosome assay

“…Exosomes, which are nanoscale liquid biopsy biomarkers secreted by cells, are found in a variety of body fluids with high abundance and stability, and the minimal‐invasive approach 1 . Because of their roles in intercellular communication, angiogenesis, and cancer metastasis, 2,3 exosomes are very suitable target for early cancer screening, diagnosis, and disease surveillance 4 . Recently, many studies have explored the screening and detection methods using tumor‐derived exosomes 5,6 .…”

“…1 Because of their roles in intercellular communication, angiogenesis, and cancer metastasis, 2,3 exosomes are very suitable target for early cancer screening, diagnosis, and disease surveillance. 4 Recently, many studies have explored the screening and detection methods using tumor-derived exosomes. 5,6 However, less specific, less sensitive, and less practical methods, such as nanoparticle tracking analysis (NTA), 7 flow cytometry (FCM), 8 and ultracentrifugation have resulted in unique clinical guidance for early warning, cancer treatment, and prognosis, especially when cancer cells secrete fewer exosomes, 9 thereby making it more difficult to detect the exosomes, efficiently and sensitively.…”