Hemozoin-generated vapor nanobubbles for transdermal reagent- and needle-free detection of malaria

Abstract

Successful diagnosis, screening, and elimination of malaria critically depend on rapid and sensitive detection of this dangerous infection, preferably transdermally and without sophisticated reagents or blood drawing. Such diagnostic methods are not currently available.Here we show that the high optical absorbance and nanosize of endogenous heme nanoparticles called "hemozoin," a unique component of all blood-stage malaria parasites, generates a transient vapor nanobubble around hemozoin in response to a short and safe near-infrared picosecond laser pulse. The acoustic signals of these malaria-specific nanobubbles provided transdermal noninvasive and rapid detection of a malaria infection as low as 0.00034% in animals without using any reagents or drawing blood. These on-demand transient events have no analogs among current malaria markers and probes, can detect and screen malaria in seconds, and can be realized as a compact, easy-to-use, inexpensive, and safe field technology.

In vivo microscopy of hemozoin: towards a needle free diagnostic for malaria

“…This approach is made feasible by exploiting the endogenous optical properties of hemozoin. The needle-free detection of hemozoin has previously been demonstrated in vivo using magneto-optical and opto-acoustical techniques [8,9], however these approaches use expensive components with significant power requirements making them difficult to implement in low resource settings where malaria is endemic. The design of the MVM was chosen to avoid the need for elaborate alignment or use of costly optical elements and detectors.…”

“…Owing to its crystalline nature, hemozoin is a highly scattering, birefringent material with strong optical absorbance and paramagnetic properties, making it an ideal candidate for in vivo optical interrogation [5,6]. Hemozoin has been explored as an endogenous malaria optical biomarker using laser desorption mass spectrometry, magnetooptic detection, and vapor nanobubble acoustical detection [7][8][9]. In this work, we explore the use of in vivo microscopy to detect hemozoin circulating in the microvasculature.…”

Rapid transdermal bloodless and reagent-free malaria detection

“…(D) An acoustic trace is obtained with an ultrasound transducer that remotely detects pressure transients emitted during bubble expansion and collapse. 26 The animals were studied with a miniature probe which comprised an optical fiber and ultrasound detector ( Figure 3). A pulsed laser was coupled to a 100 µm multi-mode optical fiber (M83L01, Thorlabs Inc., Newton, NJ) for hemozoin excitation.…”

“…Note that the H-VNB has selectively destroyed the iRBC but did not damage an adjacent uninfected RBC (Figures 4B & C).The principal conclusion to be drawn from Figure 4 is that iRBCs selectively generated H-VNBs, which were clearly discernible in individual cells even in the ring stage while the uninfected cell produced no signal. 26 The excitation wavelength dependence of H-VNBs was investigated for isolated hemozoin nanocrystals and compared to those for uninfected RBCs ( Figure 5). In contrast with RBCs, the hemozoin yielded a very narrow, 8 nm wide, spectral peak for H-VNBs in the near-infrared at 672 nm ( Figure 5).…”

Characterization of periodic cavitation in optical tweezers

“…These bubbles have been used in many different applications where fast actuation of liquid or where impulsive forces are required at a microscopic length scale. For example, in high speed microfluidics [2] and micro-pumps [3], cell membrane permeabilization [4,5] and cell lysis [6], red blood cell stretching and poration [7,8], malaria detection [9], bending of carbon nanotubes and nanowires [10,11].…”