The cause and manner of a death are not always evident, even after visual examination and dissection and examination under the microscope. From 1800 onward, scientific investigators continually devised procedures and instruments, technologies of visibility to reveal what the naked eye could not see. Chemical analysis helped detect traces of poison in the victims body. Microscopes made it possible to see tiny lesions, crystals, and hairs. Spectroscopic analysis of blood and other materials helped match trace elements linking victim and killer. As commercially manufactured poisons became increasingly available in the 19th century, poisoning became known as a modern and disturbingly hard to detect method of killing. In response, researchers developed toxicology as a specialized field of forensic medicine, and devised specific tests for poison, most famously the 1836 Marsh Test for arsenic. The new science of toxicology was plagued by difficulties. In the courtroom and laboratory, seemingly reliable tests were shown to be flawed.

But, over time, toxicology trials led to better knowledge of the action of poisons and better methods of chemical analysis. The Industrial Revolution introduced cheap poisons into homes, factories, and farms. To prevent accidents, poisons were sold in colorful and distinctively shaped bottles. But toxic substances were also used in widely available medical preparations, which poisoners could use to dispatch their victims. Mid 19th century improvements enabled physicians to use microscopy in criminal investigations. The microscope made it possible to view tiny lesions, crystals, microorganisms, and the characteristics of hairs and fibers. By the mid 20th century, investigators were using microscopes to study tissues, wounds, and fluids from victims and suspects; to identify poisons in and around the victims body, to examine minute amounts of trace elements; and to link the victims body to the perpetrator and crime scene.

Spectroscopy was born in the mid 17th century, when Isaac Newton discovered that a prism divides white light into constituent colors. Subsequent researchers discovered that specific substances, subjected to flame, give off unique patterns of light that show characteristic emission bands and absorption lines when cast through a prism. By the 1870s and 1880s, spectroscopy seemed a promising new forensic technology. Further work on spectra analysis led to spectrophotometry and, more recently, mass spectrometry. In tandem with gas chromatography, mass spectrometry is now often used to identify and match organic and inorganic substances for forensic purposes.