The present invention relates to the discovery that measurement of the level of cytochrome c (Cyt-C) in the plasma can be used as a diagnostic signature to predict antiretroviral therapy (ART) toxicity in human immunodeficiency virus (HIV) infected patients. Thus, in various embodiments described herein, the methods of the invention relate to methods of diagnosing a HIV patient with ART toxicity, methods of predicting a patient's risk of having or developing toxicity for ART, methods of assessing if a patient will benefit from a change in the treatment strategies by adjusting the dosage and/or changing the medication or even terminating of ART, and methods of predicting antiretroviral drugs propensity for causing mitochondrial toxicity. Furthermore, the invention encompasses a diagnostic kit for carrying out the aforementioned methods.

Devices, systems, methods, and kits configured to perform bioassays on live, intact tissue for precision bioanalysis in vitro are described. These approaches enable precision oncology by capturing determinants of therapeutic response to functional drug testing, such as viability and molecular signal generation, that can depend on tissue architecture, tumor heterogeneity, and the tumor microenvironment. The disclosure provides electrochemical aptamer sensors integrated into arrays of microfluidic traps for the analysis of micro-dissected tumors, as an example. The sensors are utilized with an example of periodic monitoring of cytochrome c (Cyt-C), a soluble cell death indicator, released by micro-dissected tumors.

The present invention relates to a protein-immobilized membrane (14) including a cell membrane homologous layer (14A) and a protein (14B) immobilized to the cell membrane homologous layer (14A), where the protein contains cytochrome or a cytochrome complex. The present invention also relates to a method for forming a protein-immobilized membrane (14), and an enzyme-immobilized electrode and a biosensor (X1) provided with a protein-immobilized membrane (14). Preferably, the cell membrane homologous layer (14A) may contain a phospholipid polymer, and the protein (14B) may be CyGDH including an subunit having a glucose dehydrogenase activity and cytochrome C having a function of electron transfer.

The present disclosure is directed to nonporous polymer particles having an average particle size of 1 to 10 microns and being functionalized with an enzyme, such as trypsin. The enzyme-immobilized particles, and immobilized enzyme reactors thereof, can be used in methods for on-line protein digestion.