Highly Specific, Single‐step Cancer Cell Isolation with Multi‐Aptamer‐Mediated Proximity Ligation on Live Cell Membranes

Abstract

A single‐step method for isolation of specific cells based on multiple surface markers will have unique advantages because of its scalability, efficacy, and mildness. Herein, we developed multi‐aptamer‐mediated proximity ligation method on live cell membranes that leverages a multi‐receptor co‐recognition design for enhanced specificity, as well as a robust in situ signal amplification design for improved sensitivity of cell isolation. We demonstrated the promising efficacy of our method on differentiating tumor cell subtypes in both cell mixtures and clinical samples. Owing to its simple and fast operation with excellent cell isolation sensitivity and accuracy, this approach will have broad applications in biological science, biomedical engineering, and personalized medicine.

DNA-based customized functional modules for signal transformation

“…The general strategy for obtaining this information involves collecting information on a recognition target at a small distance. Researchers have used antibodies or aptamers to sense target membrane proteins and then integrate information on their co-existence ( Figure 11A ) which hybridization chain reaction (HCR) and rolling circle amplification (RCA) have been chosen to achieved signal amplification ( Chang et al, 2019 ; Gao et al, 2020 ). In 2022, Söderberg’s group reported a fantastic strategy called MolBoolean ( Figure 11B ): this is a method that can detect interactions between endogenous proteins in various subcellular compartments.…”

“…(A) Information will be output if there is co-recognition. ( Chang et al, 2019 ; Gao et al, 2020 ). (B) Concomitant information will be inserted if there is a potential interaction; with the extension of the sequence, the interaction will be reported.…”

An automated DNA computing platform for rapid etiological diagnostics

“…DNA-based molecular computation relies on DNA as hardware and biochemical reactions as software and has been experimentally proven to be a powerful tool for implementing complex computation on different substrates toward various applications, such as solving mathematical problems, recognizing complicated patterns, and intelligent delivery of drugs (20)(21)(22)(23)(24)(25)(26)(27). With the development of DNA programming methods, different logical connectives (e.g., AND, OR, and NOT) and algorithms, such as weighting, summing, and subtraction, can be implemented at the molecular level without human intervention (28)(29)(30). In principle, DNA molecular computing can extend the applications of diagnostic methods from single to multiple markers, as well as integrate the information encoded in a multimarker signature with logical analysis for more intelligent diagnostics.…”

Sensitive Logic Nanodevices with Strong Response for Weak Inputs

“…Various label‐free logic platforms, which make its output signals (OSs) easily observed and facilitate the application of DNA computing in point‐of‐care diagnostics, [22–24] have been fabricated. Exquisite two‐input or three‐input AND logic devices, motivated by endogenous substances of cells, have also successfully been employed for subcellular imaging, [25, 26] cargo release, [27, 28] or cell classification [16, 29–31] . Even so, there are challenges that still needed to be solved immediately.…”