Multiplexed Chip System for Analysis of Drug Activity in Cell Extracts

Description:

This technology uses multielectrode chips with DNA monolayers to analyze drug activity of DNA-damaging cancer treatments to inform therapeutic decisions for personalized medicine. Due to the unpredictability of cancer drugs, it is difficult to identify which therapy will work most effectively for each individual while producing minimal side effects. Although a number of cancer treatments induce DNA damage to bring about cell death, there has yet to be a way to rapidly evaluate drug activity across both healthy and cancerous cell lines – until now. The presented platform resolves these issues by providing modular control of intracellular components, including anticancer drugs and immunotherapies such as beta-lapachone (β-lap), cisplatin, or methotrexate. The active monitoring and manipulation of these mechanisms enables swift systematic investigation of patient-specific biological drug pathways. This system is not only useful for enhancing patient care, but may also be used to develop anticancer therapies on a broad scale – especially since it may be applied in a multiplexed way, such that many drugs can be evaluated in rapid succession.

Technical Summary:

The drug reactions are analyzed with DNA monolayers on a multiplexed chip – these are arranged in a manner that considers the natural biological separation of components to maintain biological relevance. The monolayers are evaluated and easily monitored with an electrochemical signal that is sensitive to changes in the structure and integrity of DNA base pairs. When a drug reaction damages a portion of the DNA monolayers, it triggers nuclear repair proteins to remove the damage, thereby lowering the electrochemical signal on the chip. The impact of adding drugs, such as β-lap, to each lysate is quantified through the electrochemical signal changes arising from drug-induced DNA damage. This device is ready to be implemented as a standard tool for analyzing the drug activity of cancer-selective treatments in the lab, enabling quantitative identification of effective drugs for patients while minimizing side effects.

Value Proposition:

This device quickly & quantitatively tracks the underlying biological activities of existing cancer drugs with modular control of intracellular components, thereby allowing refinement of targeted cancer lethality. Such information enables physicians to tailor cancer therapies to patients – identifying the treatment that is most effective against the specific cancer and poses minimal risk of side effects.

Applications:

Personalized Healthcare – Modular control of intracellular components enables refinement of targeted cancer lethality to enhance patient outcomes
Drug Evaluation – Enables investigation of biological pathways of drug activity to understand mechanisms of action, particularly with respect to DNA damage
Therapeutic Monitoring – Can be used to monitor, assess efficacy of drug therapies & diagnose diseases

Key Benefits:

Efficient Analysis - The activity of a variety different drugs can be analyzed simultaneously in a rapid manner.
Customizable - Modular control of intracellular components enables systematic investigation of biological pathways of drug activity
Targeted Medicine - The chip can be used to customize specific therapies for individuals based on their differing DNA structures.

Publication:

Kahanda, Dimithree, et al. “Following Anticancer Drug Activity in Cell Lysates with DNA Devices.” Biosensors and Bioelectronics, vol. 119, 30 July 2018, pp. 1–9., doi:10.1016/j.bios.2018.07.059.