Light chain amyloidosis is a life-threatening disease and is the most common form of systemic amyloidosis. This disease involves antibody light chains misfolding into non-functional aggregates and plaques that can lead to tissue and organ failure. When systemic, these plaques can deposit anywhere, making diagnosis and treatment difficult. Adding to the complexity, the aggregation mechanism is still not well-understood, however, it is believed that aggregation is accelerated by destabilization of the antibody’s native structure. Therefore, in this study we characterized the structures of 3 different isotypes of light and variable chain antibody domains that were based on patients with amyloidosis (AL) that are disease positive, multiple myeloma (MM) that are disease-prone, and germline (GL) that are non-disease-prone. This was accomplished using the novel infrared technique of microfluidic modulation spectroscopy and allowed us to measure the higher order structures of these 3 clinically relevant antibody isotypes. We determined that the amyloidosis-causing isotypes have more unordered regions and intermolecular beta-sheet structures, supporting the hypothesis that destabilizing the native structure leads to intermolecular aggregates. Structural differences and trends were also measured using circular dichroism, however, the limited information regarding beta sheets and unordered regions made it difficult to identify any trends or conclusions among the 3 different disease isotypes. The detailed structural information provide by Microfluidic Modulation spectroscopy is crucial for understanding the aggregation mechanism and providing insights into potential therapeutic strategies.