FATIMA TOOR, UNIVERSITY OF IOWA
Liquid biopsies have the potential to revolutionize cancer care for patients. Our team at the University of Iowa — which includes me, pharmaceutical sciences professor Aliasger Salem, and Dr. Pashtoon Kasi of the Department of Internal Medicine — is developing a silicon nanowire (SiNW) biosensor point-of-care platform to overcome the current limitations of detecting protein and circulating tumor DNA (ctDNA) biomarkers in liquid biopsies. While some factors are disease-specific (for example, shedding of DNA by tumor type), others are treatment related. Timing of the assay can drastically affect the agreement within these assays because the shedding of DNA goes down markedly once a person starts — and responds to — treatment. As the treatments are initiated, the amount of ctDNA decreases, explaining the reduced ability of the commercially available assays to pick up these cancer biomarkers. Furthermore, the average cost of a biopsy can be around a few thousand dollars, with a turnaround of 10 to 14 days. The proposed biosensor technology platform will directly address these limitations.
The successful completion of our studies will result in an integrated biosensor that has been fully characterized and optimized for detection of a range of existing protein and ctDNA-based cancer biomarkers.
The biosensor platform is based on an inexpensive and scalable material (i.e., Si and manufacturing process flow) that would result in a time- and cost-effective analysis of liquid biopsies. In contrast to ELISA (enzyme-linked immunosorbent assays) and whole-genome-based NGS (next-generation sequencing) assays, a SiNW biosensor has the following advantages: It is capable of dynamic detection and can be regenerated for reuse; it provides concentration-dependent data; cross-binding reactivity can be studied for each device; it is more sensitive, requiring a much lower concentration of ctDNA (fM as opposed to nM); and it is low cost.
SiNW biosensors to date have been based on horizontally oriented nanowires that require electrical contacts on both sides, resulting in a complex and expensive device-fabrication process that limits the number of nanowires per unit. We address this challenge of contacting the nanowires by using vertically oriented nanowires and a unique device design that enables us to electrically and optically probe millions of nanowires concurrently. Such a simple and scalable approach would make the commercialization of a SiNW-based biosensor a reality. Theoretically, each nanowire acts as an anchor for the target biomarker; hence, the sensitivity can potentially be increased manifold (~fM detection limit) relative to existing SiNW sensors that use a few nanowires per sensor. The SiNW biosensor would have the ability to detect both ctDNA and protein-based biomarkers in an inexpensive, sensitive, and rapid manner.
The electrical device design of the SiNW biosensor is based on a p-n junction diode architecture, which is the same as that used for solar cells. Our recently published work1 demonstrates the proof-of-concept of the biosensor platform for detecting protein-based prostate-specific antigen (PSA). The SiNW-based biosensor presented here uses a solar cell as a transducing element. The NW surfaces are modified by anchoring monoclonal antibodies specific for PSA. This surface modification allows for an increase in the binding of PSA to the SiNW structures, which causes an increase in short-circuit density of the solar cell when exposed to light and PSA. The antibody and antigen attachment is dubbed the lock-and-key mechanism, with antibody and antigen interacting by spatial complementarity.
Targeted treatment plans based on surgery or existing chemotherapies are not personalized. With liquid biopsies, the patient may receive an agile treatment plan enabled by the SiNW sensor, which allows for measurement of up- or down-regulation of the cancer biomarkers and a personalized treatment plan. The successful completion of our studies will result in an integrated biosensor that has been fully characterized and optimized for detection of a range of existing protein and ctDNA-based cancer biomarkers.
Meet the author
Fatima Toor is assistant professor of electrical
and computer engineering and physics and astronomy at the University of Iowa (UI) in Iowa City, Iowa. She is also an affiliate member of the Holden Comprehensive Cancer Center Experimental Therapeutics Program at the UI Hospitals & Clinics; email: [email protected].
Reference
1. R. Smith et al. (Oct. 29, 2018). Surface modifying doped silicon nanowire based solar cells for applications in biosensing. Adv Mater Technol, Vol. 4, Issue 2, www.doi.org/10.1002/admt.201800349.
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