6 IEEE TRANSACTIONS ON NANOBIOSCIENCE, VOL. 2, NO. 1, MARCH 2003 Using a System-on-a-Chip Implantable Device to Filter Circulating Infected Cells in Blood or Lymph Darrin M. Hanna, Member, IEEE, Barbara A. Oakley*, Senior Member, IEEE, and Gabrielle A. Stryker Abstract—This paper describes a system on a chip (SoC) that makes use of nanoscale cellular adhesion mechanisms in an inte- grated electronic microsystem to filter infected cells from blood or lymph. An example of a human immunodeficiency virus-specific SoC is explored in depth. Such systems work in vivo, and blood and lymph are filtered on a continuous basis. With the intelligence on the chip, captured cells can be identified and lyzed, expelled, or otherwise acted upon. These types of systems transfer the burden of research from traditional chemotherapy to bioengineering and system design. Index Terms—Biological microelectromechanical system (bioMEMS), engineered antibodies, human immunodeficiency virus (HIV), system on a chip. I. INTRODUCTION C HEMOTHERAPY has provided a powerful tool in the medical arsenal against infectious pathogens and malignant processes. However, side effects can be devastating, ranging from severe gastrointestinal problems to headaches, nausea, memory loss, hair loss, and rashes [1]–[4]. Long-term side effects include life-threatening liver, kidney, and heart dis- ease [5], [6]. Recently, several research groups have explored engineering implantable chips for biomedical applications [7]–[9]. Using current advances in intelligent embedded technology, it is possible for bioelectronics utilizing nanoscale components to be developed into a tool for fighting infectious pathogens and malignant processes; this is part of an evolution in treatment that could have the same efficacy as chemotherapy without the severe side effects. Leukemia and several infectious diseases are characterized by diseased cells circulating in the bloodstream. These cells can be distinguished from healthy cells through specific cell sur- face proteins. Examples include multiple leukemias, human T cell leukemia virus (HTLV), Epstein–Barr virus, malaria, and human immunodeficiency virus (HIV). Information regarding distinctive cell surface proteins for some of these diseases is well known. For example, a malaria-harboring red blood cell has a stiffer membrane and parasite-specific surface knobs that dif- ferentiate it from a normal red blood cell [10]. Using new tech- Manuscript received January 25, 2003. This work was supported in part by the National Institutes of Health under Grant R21 EB00672-01 and by the National Science Foundation under Grant 9977859. Asterisk indicates corresponding author. D. M. Hanna is with the School of Engineering and Computer Science, Oak- land University, Rochester, MI 48309 USA. *B. A. Oakley is with the School of Engineering and Computer Science, Oak- land University, Rochester, MI 48309 USA (e-mail: oakley@oakland.edu). G. A. Stryker is with the Department of Biological Sciences, Oakland Uni- versity, Rochester, MI 48309 USA. Digital Object Identifier 10.1109/TNB.2003.810160 Fig. 1. Algorithm for a system on a chip used to act on specific pathogens. nology in miniaturization and artificial intelligence, it is pos- sible to use information such as this to distinguish cells at molec- ular scales. More specifically, it is now possible to create a bio- logical microelectromechanical system (bioMEMS) that could eliminate cells involved in certain diseases. Fig. 1 shows the logic behind a general implantable device for selectively iden- tifying altered-self or infectious cells and reacting accordingly. This paper was written to outline the possibility of a unique alternative to chemotherapy-like therapies that makes use of an implanted system on a chip (SoC) to selectively capture and kill diseased cells that circulate either in the human blood stream or lymph. Some of the component mechanisms of the SoC are extant, others are proposed for the first time in this paper. The advantages of an SoC alternative to chemotherapy and related types of therapy are notable: most important are that the toxic side effects from drugs are eliminated, and an alternate pathway for treatment is presented with reduced side effects or (through the induction of apoptosis—programmed cell death) virtually no side effects. In brief, the method calls for placing a coating of a specific receptor or ligand to a target cell surface protein onto a surface of a silicon chip—part of the SoC. The specific receptor on the SoC will capture the cells of interest. The coated silicon chip would be part of an intelligent system for detecting and acting on bound cells. One method of killing a cell is through lysing the cell membrane. A lysing mechanism would consist of a series of electrodes implanted in the surface of the SoC that could irreversibly electroporate attached cells. An alternate lysing mechanism planned for future research would involve inducing apoptosis through injection of apoptosis-inducing protein into the cell upon binding. The system works, in its most simplistic form, by allowing blood or lymph containing 1536-1241/03$17.00 © 2003 IEEE